Back Clinical Neurophysiology Support. El Paso, TX. Chiropractor, Dr. Alexander Jimenez akukambirana Clinical neurophysiology. Dr. Jimenez adzafufuza zofunikira zachipatala ndi ntchito zogwirira ntchito za mitsempha ya mitsempha ya m'mphepete mwa msana, msana, ubongo, ndi ubongo pokhudzana ndi matenda a visceral ndi musculoskeletal. Odwala adzalandira chidziwitso chapamwamba cha anatomy, genetics, biochemistry, ndi physiology ya ululu wokhudzana ndi matenda osiyanasiyana a matenda. Zakudya zamagetsi zokhudzana ndi nociception ndi ululu zidzaphatikizidwa. Ndipo kukhazikitsidwa kwa chidziwitsochi m'mapulogalamu azachipatala kudzatsindika.
Gulu lathu limanyadira kwambiri kubweretsa mabanja athu ndi odwala ovulala okha ma protocol otsimikiziridwa a chithandizo. Pophunzitsa za ukhondo wathunthu monga moyo, sitisinthanso miyoyo ya odwala komanso mabanja awo. Timachita izi kuti tifikire anthu ambiri a El Pasoans omwe amatifuna, mosasamala kanthu za zomwe angakwanitse. Kuti mupeze mayankho a mafunso aliwonse omwe mungakhale nawo chonde imbani Dr. Jimenez pa 915-850-0900.
"Malamulo a zisankho zachipatala, gulu la ululu wa msana ndi kulosera za zotsatira za chithandizo: Kukambitsirana kwa malipoti aposachedwapa m'mabuku okonzanso"
Kuchuluka kwa njira zamagulu kwa odwala omwe ali ndi vuto la lumbar pogwiritsa ntchito ma syndromes a McKenzie, kupweteka kwapakhosi, kusokoneza, ndi kukhazikika kwa malamulo olosera zachipatala.
Zolinga zinali (1) kuti adziwe kuchuluka kwa odwala omwe ali ndi vuto la m'chiuno omwe angagawidwe ndi McKenzie syndromes (McK) ndi pain pattern classification (PPCs) pogwiritsa ntchito njira zowunika za Mechanical Diagnosis and Therapy (MDT), kusintha, ndi kukhazikika kwachipatala. malamulo (CPRs) ndi (2) pamtundu uliwonse wa Man CPR kapena Stab CPR, dziwani kuchuluka kwa magulu pogwiritsa ntchito McK ndi PPC.
Ma CPRs ndi zitsanzo zamakono zamakono komanso zowonjezereka zomwe gulu la zizindikiro za odwala omwe amadziwika ndi zizindikiro zachipatala ndi zizindikiro zimagwirizanitsidwa ndi kuneneratu kopindulitsa kwa zotsatira za odwala.
Ma CPR awiri osiyana adapangidwa ndi ochita kafukufuku kuti adziwe odwala omwe angayankhe bwino pakuwongolera.33,34 Flynn et al. adapanga CPR yogwiritsira ntchito pogwiritsira ntchito njira zisanu, mwachitsanzo, palibe zizindikiro pansi pa bondo, zizindikiro zaposachedwapa (<16 masiku), mafunso otsika-kupewa kuopa chikhulupiliro36 ntchito (<19), hypomobility ya lumbar spine, ndi chiuno chamkati. kuzungulira ROM (> 35 kwa chiuno chimodzi) .33
CPR ya Flynn idasinthidwa pambuyo pake ndi Fritz et al. pazigawo ziwiri, zomwe sizinaphatikizepo zizindikiro pansi pa bondo ndi zizindikiro zaposachedwapa (<16 masiku), monga njira ina yochepetsera kuchepetsa katundu wachipatala kuti azindikire odwala omwe ali ndi chithandizo chamankhwala omwe amatha kuyankha kuponderezedwa.34 zabwino
"Potentia.l Pitfalls Of Clinical Prediction Rules"
Kodi Malamulo Olosera Zachipatala Ndi Chiyani?
Ulamuliro wolosera zachipatala (CPR) ndikuphatikizana kwazomwe zapezeka m'matenda omwe awonetsa mowerengetsera zolosera zatanthauzo pozindikira matenda omwe asankhidwa kapena kuwunika kwa wodwala yemwe wapatsidwa chithandizo chapadera 1,2. Ma CPR amapangidwa pogwiritsa ntchito njira zowerengera zosiyanasiyana, amapangidwa kuti aziwunika kuthekera kodziwikiratu kwa magulu osankhidwa amitundu yosiyanasiyana yazachipatala3,4, ndipo cholinga chake ndi kuthandiza azachipatala kupanga zisankho mwachangu zomwe nthawi zambiri zimakhala zokondera5. Malamulowa ndi a algorithmic m'chilengedwe ndipo amaphatikiza chidziwitso chofupikitsidwa chomwe chimazindikiritsa ziwerengero zocheperako zomwe zimazindikiridwa ndi chikhalidwe6.
Ngakhale pali mtsutso wochepa womwe umapangidwa mosamala ma CPRs ukhoza kupititsa patsogolo machitidwe azachipatala, malinga ndi chidziwitso changa, palibe malangizo omwe amafotokoza zofunikira za njira za CPR kuti zilowerere m'malo onse azachipatala. Malangizo amapangidwa kuti apititse patsogolo kukhazikika kwa kapangidwe ka maphunziro ndi malipoti. Mkonzi wotsatirawu akuwonetsa zovuta zomwe zingachitike mu CPRs zomwe zingafooketse kwambiri kusamutsa kwa algorithm. Mkati mwa gawo la kukonzanso, ma CPR ambiri akhala akulembera; motero, ndemanga zanga apa zikuwonetseratu za CPRs zovomerezeka.
Mipata ya Methodological
Ma CPRs adapangidwa kuti afotokozere mosiyanasiyana mawonekedwe kuchokera kwa anthu ambiri omwe akuyembekezeka kusankhidwa motsatizana5,15. Kawirikawiri, chiwerengero cha anthu chomwe chikugwiritsidwa ntchito chimakhala kagawo kakang'ono kachitsanzo chachikulu ndipo chikhoza kuimira gawo lochepa chabe la zochitika zenizeni za tsiku ndi tsiku za dokotala. Malo ndi malo a chitsanzo chachikulu ayenera kukhala generalizable15,16, ndipo kafukufuku wotsatira wovomerezeka amafuna kuunika kwa CPR m'magulu osiyanasiyana odwala, m'madera osiyanasiyana, komanso ndi gulu la odwala omwe amawonedwa ndi madokotala ambiri16. Chifukwa ma CPR ambiri amapangidwa potengera gulu losiyana kwambiri lomwe lingathe kuwonetsa kapena kusawonetsa kuchuluka kwa odwala omwe ali ndi odwala, ma spectrum transportability17 a ma algorithms apano a CPR angakhale ochepa.
Malamulo olosera zachipatala amagwiritsa ntchito njira zotsatila kuti adziwe momwe ntchitoyo ikuyendera. Miyezo ya zotsatira iyenera kukhala ndi tanthauzo limodzi la magwiridwe antchito5 ndipo imafunikira kuyankha kokwanira kuti itenge kusintha koyenera kwa chikhalidwe14; kuphatikiza apo, miyeso iyi iyenera kukhala ndi gawo lodulidwa lomangidwa bwino16,18 ndikusonkhanitsidwa ndi woyang'anira wakhungu15. Kusankhidwa kwa mphambu yoyenerera ya nangula yoyezera kusintha kwenikweni kukukambitsirana19-20. Zotsatira zambiri za zotsatira zimagwiritsa ntchito mafunso okhudzana ndi kukumbukira odwala monga chiwerengero cha padziko lonse cha kusintha kwa chiwerengero (GRoC), chomwe chiri choyenera pamene chikugwiritsidwa ntchito kwa nthawi yochepa koma chimakhala ndi malingaliro okumbukira pamene akugwiritsidwa ntchito mu kusanthula kwa nthawi yaitali19-21.
Chomwe chingathe kubwereranso kwa CPRs ndikulephera kusunga khalidwe la mayesero ndi miyeso yomwe imagwiritsidwa ntchito ngati zolosera mu ndondomeko. Chifukwa chake, kuyesa kwamawonekedwe ndi miyeso ziyenera kukhala zodziyimira pawokha pazachitsanzo16; chilichonse chizichitika mwatanthauzo, movomerezeka4; asing'anga kapena oyang'anira deta ayenera kuchititsidwa khungu kuti asawone zotsatira za wodwalayo ndi momwe alili22.
magwero
Zomwe Zingatheke Za Malamulo Olosera Zachipatala; The Journal of Manual & Manipulative Therapy Volume 16 Number Two [69]
Jeffrey J Hebert ndi Julie M Fritz; Malamulo a chipatala, magulu a ululu wa msana ndi kulosera za zotsatira za chithandizo: Kukambitsirana kwa malipoti aposachedwapa m'mabuku okonzanso.
Mavuto mu Umoyo Wamaganizo ndi Kusokonezeka kwa Maganizo
Ngakhale kuti matenda amisala ali ndi vuto lokhudzana ndi matenda kuposa gulu lina lililonse lachipatala, 1 kusiyana kwa ulemu kumawonekerabe pakati pa thanzi la thupi ndi maganizo m'madera ambiri kuphatikizapo ndalama zofufuza2 ndi zofalitsa.3 Pakati pa zovuta zomwe umoyo wamaganizo umakumana nazo ndikusowa za mgwirizano wozungulira magulu, matenda ndi chithandizo chomwe chimachokera ku kusamvetsetsa kwathunthu kwa njira zomwe zimayambitsa vutoli. Izi zikuwonekera kwambiri pazovuta zamaganizo, gulu lomwe liri ndi katundu umodzi waukulu kwambiri m'maganizo.3 Matenda ofala kwambiri a maganizo, matenda aakulu ovutika maganizo (MDD), ndi matenda ovuta kwambiri, omwe mpaka 60 peresenti ya odwala angakhale nawo. kukana kulandira mankhwala komwe kumatalikitsa ndi kuipiraipira.4 Pazovuta za kupsinjika maganizo, komanso m'mbali zambiri za thanzi labwino la maganizo, zotsatira za chithandizo zikhoza kukhala zabwino pozindikira kuti pali mitundu ina yamphamvu, yofanana m'magulu (ndi m'magulu onse) ozindikira matenda, omwe mankhwala amawagwiritsa ntchito. akhoza stratified. Pozindikira izi, zoyesayesa zapadziko lonse zofotokozera magawo ogwirira ntchito tsopano zikuyenda, monga njira zowunikira kafukufuku.5 Zakhala zikudziwika kuti zizindikiro za biologic ndizofunikira kwambiri pazovuta zamaganizo.6
Kuwongolera Mayankho ku Chithandizo cha Kupsinjika Maganizo
Ngakhale pali njira zambiri zothandizira kuvutika maganizo kwakukulu, pafupifupi gawo limodzi mwa magawo atatu a odwala omwe ali ndi MDD amatha kukhululukidwa ngakhale atalandira chithandizo choyenera cha antidepressant malinga ndi malangizo ogwirizana komanso kugwiritsa ntchito chisamaliro choyezera, ndipo chiwerengero cha kuyankha kwamankhwala chikuwoneka chikutsika ndi chithandizo chatsopano chilichonse. .7 Kuwonjezera apo, kuvutika maganizo kosagwirizana ndi mankhwala (TRD) kumayenderana ndi kuwonjezeka kwa kuwonongeka kwa ntchito, kufa, kudwala ndi zochitika zobwerezabwereza kapena zosatha kwa nthawi yaitali. zotsatira zonse mu kukhumudwa. Ngakhale kuti TRD ili ndi zovuta zambiri, kafukufuku m'derali ndi ochepa. Tanthauzo la TRD silinakhazikitsidwe, mosasamala kanthu za kuyesayesa koyambirira: 8,9 njira zina zimafuna chithandizo chimodzi chokha chomwe chimalephera kukwaniritsa kuchepetsa zizindikiro za 4% (kuchokera muyeso yovomerezeka ya kupsinjika maganizo), pamene ena amafuna kuti asakwaniritse chikhululukiro chonse. kapena kusagwirizana ndi osachepera awiri omwe amayesedwa mokwanira kuti athetse kupsinjika maganizo a magulu osiyanasiyana mkati mwa gawo lomwe liyenera kuganiziridwa kuti ndi TRD.50 Kuwonjezera apo, ndondomeko ndi kulosera za kukana chithandizo kumatheka powonjezera zizindikiro zazikulu zachipatala za kuuma ndi kusakhazikika kwa chiwerengero cha mankhwala olephera. .4,10 Komabe, kusagwirizana kumeneku kumatanthauzo kumapangitsa kutanthauzira mabuku ofufuza pa TRD kukhala ntchito yovuta kwambiri.
Kuti muwongolere kuyankha kwamankhwala, ndizothandiza kuzindikira zolosera zomwe zingachitike chifukwa chosayankha. Zina zolosera za TRD zakhala zikudziwika, kuphatikizapo kusowa kwa chikhululukiro chonse pambuyo pa zochitika zam'mbuyomu, nkhawa ya comorbid, kudzipha ndi kuyamba kuvutika maganizo, komanso umunthu (makamaka kutsika pang'ono, kudalira malipiro otsika ndi neuroticism) ndi chibadwa.12 Zotsatirazi zimatsimikiziridwa ndi ndemanga zopanga umboni padera pa pharmacologic13 ndi psychological14 chithandizo cha kuvutika maganizo. Mankhwala oletsa kupsinjika maganizo ndi chidziwitso-makhalidwe ochiritsira amasonyeza mphamvu zofananira, 15 koma chifukwa cha njira zawo zosiyana zogwirira ntchito zikhoza kuyembekezera kukhala ndi zolosera zosiyana siyana. Ngakhale kuti kuvulala koyambirira kwa nthawi yayitali kumagwirizanitsidwa ndi zotsatira zachipatala zosauka komanso kuchepetsa mayankho ku chithandizo, zizindikiro zoyamba za 16 zimasonyeza kuti anthu omwe ali ndi vuto laubwana akhoza kuyankha bwino maganizo kusiyana ndi mankhwala ochiritsira mankhwala. stratification wa mankhwala wafika mchitidwe wachipatala.17
Ndemangayi ikuyang'ana pa umboni wotsimikizira kugwiritsa ntchito ma biomarkers ngati zida zothandiza zachipatala kuti zithandizire kuyankha kwamankhwala kupsinjika.
Biomarkers: Machitidwe ndi Magwero
Ma biomarkers amapereka chandamale chodziwikiratu zomwe zidzachitike pakuchitapo kanthu kosiyanasiyana.19 Umboni womwe ulipo mpaka pano ukuwonetsa kuti zolembera zomwe zikuwonetsa ntchito ya zotupa, neurotransmitter, neurotrophic, neuroendocrine ndi kagayidwe kachakudya zimatha kuneneratu zomwe zidzachitike m'maganizo ndi thupi mwa anthu omwe ali ndi nkhawa pakali pano. , koma pali kusagwirizana kwakukulu pakati pa zomwe zapezedwa.20 Mu ndemanga iyi, timayang'ana pa machitidwe asanu a biologic awa.
Kuti timvetse bwino njira za mamolekyu ndi zomwe zimawathandiza pa matenda a maganizo, tsopano ndi kofunika kuyesa magawo angapo a biologic, m'njira yomwe imatchedwa "omics" njira.21 Chithunzi 1 chimapereka chithunzithunzi cha zosiyana Magawo a biologic omwe machitidwe asanu aliwonse angawunikidwe, ndi magwero a zolembera zomwe kuwunikaku kungachitike. Komabe, dziwani kuti ngakhale dongosolo lililonse likhoza kuyesedwa pa mlingo uliwonse wa omics, magwero abwino a kuyeza amasiyana momveka bwino pamlingo uliwonse. Mwachitsanzo, neuroimaging imapereka nsanja yowunika momwe ubongo umagwirira ntchito kapena momwe amagwirira ntchito, pomwe kuyesa kwa mapuloteni m'magazi kumawunika mwachindunji zolembera. Transcriptomics22 ndi metabolomics23 zikuchulukirachulukira, ndikuwunika kuchuluka kwa zolembera, ndipo Human Microbiome Project tsopano ikuyesera kuzindikira tizilombo tating'onoting'ono tating'onoting'ono tomwe timapangidwira mwa anthu. ; mwachitsanzo, mahomoni monga cortisol tsopano akhoza kuyesedwa mu tsitsi kapena zikhadabo (kupereka chisonyezero chosatha) kapena thukuta (kupereka muyeso wopitirira), 24 komanso m'magazi, cerebrospinal fluid, mkodzo ndi malovu.
Poganizira kuchuluka kwa magwero, milingo ndi machitidwe omwe akukhudzidwa ndi kukhumudwa, sizodabwitsa kuti kuchuluka kwa ma biomarkers omwe ali ndi kuthekera komasulira ndikokwanira. Makamaka, kuyanjana pakati pa zolembera kumaganiziridwa, ndikokayikitsa kuti kuyang'ana ma biomarker amodzi payekhapayekha kumabweretsa zopindulitsa pakuwongolera machitidwe azachipatala. Schmidt et al26 adapereka lingaliro la kugwiritsa ntchito mapanelo a biomarker ndipo, pambuyo pake, Brand et al27 adafotokoza gulu lokonzekera kutengera umboni wam'chipatala komanso wodziwikiratu wa MDD, kuzindikiritsa 16 �strong� biomarker chandamale, chilichonse chomwe sichikhala ndi chikhomo chimodzi. Amakhala ndi kuchuluka kwa imvi (mu hippocampal, prefrontal cortex ndi basal ganglia regions), kusintha kwa circadian cycle, hypercortisolism ndi mawonekedwe ena a hypothalamic pituitary adrenal (HPA) axis hyperactivation, kulephera kwa chithokomiro, kuchepa kwa dopamine, noradrenalinendo kapena 5-leacetic acid. , kuwonjezeka kwa glutamate, kuwonjezeka kwa superoxide dismutase ndi lipid peroxidation, attenuated cyclic adenosine 3?, 5? -monophosphate ndi mitogen-activated protein kinase pathway ntchito, kuwonjezeka kwa proinflammatory cytokines, kusintha kwa tryptophan, kynurenine, insulini ndi ma genetic polymorphisms. Zizindikirozi sizinagwirizane ndi mgwirizano ndipo zikhoza kuyesedwa m'njira zosiyanasiyana; zikuwonekeratu kuti ntchito yokhazikika komanso yokhazikika iyenera kuthana ndi ntchito yayikuluyi kuti iwonetsere mapindu awo azachipatala.
Zolinga za Ndemanga iyi
Monga kuwunikira mwadala, nkhaniyi ikufuna kudziwa zofunikira zonse pakufufuza kwa biomarker mu kupsinjika maganizo komanso momwe ma biomarkers ali ndi kuthekera kwenikweni komasulira kuti athandizire kuyankha kwamankhwala. Timayamba ndikukambirana zofunikira kwambiri komanso zosangalatsa zomwe tapeza m'gawoli ndikuwongolera owerenga ku ndemanga zenizeni zokhudzana ndi zolembera zoyenera ndi kufananitsa. Timalongosola zovuta zomwe zilipo panopa potsatira umboni, kuphatikizapo zofunikira zochepetsera kupsinjika maganizo. Pomaliza, timayang'ana m'tsogolo ku njira zofufuzira zofunika kwambiri kuti tikwaniritse zovuta zomwe zikuchitika komanso zomwe zimakhudza machitidwe azachipatala.
Kuzindikira Kwaposachedwa
Kusaka kwa ma biomarker othandiza azachipatala kwa anthu omwe ali ndi vuto la kuvutika maganizo kwapanga kafukufuku wambiri pazaka makumi asanu zapitazi. Mankhwala omwe amagwiritsidwa ntchito kwambiri adapangidwa kuchokera ku chiphunzitso cha monoamine cha kuvutika maganizo; Pambuyo pake, ma hypotheses a neuroendocrine adakhudzidwa kwambiri. M'zaka zaposachedwa, kafukufuku wochuluka kwambiri wazungulira malingaliro otupa a kupsinjika maganizo. Komabe, chiwerengero chachikulu cha zolemba zowunikira zowunikira zayang'ana pa machitidwe onse asanu; onani Table 1 ndi pansipa kuti mupeze zidziwitso zaposachedwa pamakina a biomarker. Ngakhale kuti amayezedwa pamiyeso yambiri, mapuloteni opangidwa ndi magazi amafufuzidwa kwambiri ndipo amapereka gwero la biomarker yomwe ili yabwino, yotsika mtengo ndipo ikhoza kukhala pafupi ndi kuthekera komasulira kusiyana ndi magwero ena; motero, tsatanetsatane waperekedwa kwa ma biomarkers omwe amazungulira m'magazi.
Pakuwunika kwakanthawi kwaposachedwa, Jani et al20 adawunikira zolembera zam'magazi zokhala ndi kupsinjika maganizo mogwirizana ndi zotsatira za chithandizo. Pa maphunziro a 14 okha omwe anaphatikizidwa (anafufuzidwa mpaka kumayambiriro kwa 2013), 36 biomarkers anaphunziridwa zomwe 12 zinali zolosera kwambiri za zizindikiro zamaganizo kapena zakuthupi pakufufuza kumodzi. Zomwe zimadziwika kuti zingakhale zoyimira chiopsezo cha kusayankhidwa zinaphatikizapo mapuloteni otupa: otsika interleukin (IL) -12p70, chiŵerengero cha lymphocyte ku chiwerengero cha monocyte; zolembera za neuroendocrine (kusagwirizana kwa dexamethasone kwa cortisol, kuchuluka kwa cortisol, kuchepa kwa mahomoni olimbikitsa chithokomiro); zolembera za neurotransmitter (otsika serotonin ndi noradrenaline); kagayidwe kachakudya (otsika kwambiri kachulukidwe lipoprotein cholesterol) ndi neurotrophic factor (kuchepetsedwa kwa S100 calcium-binding protein B). Kuwonjezera pa izi, ndemanga zina zakhala zikufotokozera za mayanjano pakati pa zizindikiro zowonjezera zamoyo ndi zotsatira za mankhwala.19,28�30 Kufotokozera mwachidule kwa zizindikiro zoyikapo mu dongosolo lililonse kumafotokozedwa m'zigawo zotsatila ndi mu Table 2.
Zotsatira Zotupa mu Kupsinjika Maganizo
Popeza kuti Smith's seminal paper ikufotokoza za macrophage hypothesis,31 mabuku okhazikitsidwawa apeza kuchuluka kwa zizindikiro zosiyanasiyana za proinflammatory kwa odwala ovutika maganizo, zomwe zakhala zikuwunikiridwa kwambiri. kulamulira anthu.32�37
IL-6 (P <0.001 muzofufuza zonse za meta; maphunziro a 31 akuphatikizidwa) ndi CRP (P <0.001; maphunziro a 20) amawoneka kawirikawiri komanso odalirika okwera kupsinjika maganizo.40 Chotupa chachikulu cha necrosis factor alpha (TNF?) chinadziwika mu maphunziro oyambirira. (P<0.001),38 koma kusiyanasiyana kwakukulu kunapangitsa kuti izi zikhale zosagwirizana ndi kafukufuku waposachedwapa (maphunziro a 31) .40 IL-1? imakhudzana kwambiri ndi kupsinjika maganizo, kuwunika kwa meta komwe kumasonyeza kuti kuvutika maganizo kwakukulu (P = 0.03), 41 kukwera kwapamwamba kokha m'maphunziro a ku Ulaya42 kapena palibe kusiyana ndi zowongolera. 40?, 1 mothandizidwa ndi zotsatira zofunikira kwambiri za IL-44 yokwezeka? ribonucleic acid kulosera kusayankhidwa koyipa kwa antidepressants; 1 zopeza zina pamwambapa zokhudzana ndi kuzungulira kwa ma cytokines opangidwa ndi magazi. Chemokine monocyte chemoattractant protein-45 yawonetsa kukwera kwa omwe akuvutika maganizo mu meta-analysis imodzi. meta-analytic level, komabe awonetsa kuthekera kosintha ndi chithandizo: IL-1 yanenedwa kuti ndi yokwezeka mwa iwo omwe ali ndi kupsinjika kwakukulu mwapang'onopang'ono komanso mwapang'onopang'ono, 39 mitundu yosiyanasiyana ya kusintha kwa IL-2 ndi interferon gamma panthawi ya chithandizo. zakhala zikuchitika pakati pa oyankha oyambirira ndi osayankha, 4 pamene IL-8 ndi IL-10 zatsika mogwirizana ndi kukhululukidwa kwa zizindikiro.8 Mu meta-analysis, kuchepa pang'ono pamodzi ndi chithandizo kwasonyezedwa kwa IL-46, IL-10?, IL- 47 ndi CRP.4 Kuwonjezera, TNF? zingachepetse ndi chithandizo cha oyankha, ndipo chiwerengero cha zizindikiro zophatikizika chikhoza kusonyeza kuwonjezeka kwa kutupa kwa odwala omwe pambuyo pake samayankha chithandizo. . Chifukwa chake, kusintha kwina kotupa panthawi yamankhwala kumatha kuchitika chifukwa cha antidepressants. Zotsatira zenizeni zotupa za antidepressants zosiyanasiyana sizinakhazikitsidwebe, koma umboni wogwiritsa ntchito ma CRP umasonyeza kuti anthu amayankha mosiyana ndi mankhwala enaake okhudzana ndi kutupa koyambirira: Harley et al2 adanena kuti chithandizo chapamwamba cha CRP chikulosera kusayankhidwa bwino kwa chithandizo chamaganizo (chidziwitso-makhalidwe kapena anthu). psychotherapy), koma kuyankha bwino kwa nortriptyline kapena fluoxetine; Uher et al48 adafotokozeranso zomwe adapeza za nortriptyline ndipo adazindikira zotsatira zotsutsana ndi escitalopram. Mosiyana ndi izi, Chang et al6 adapeza CRP yapamwamba kwambiri poyankha koyambirira kwa fluoxetine kapena venlafaxine kuposa omwe sanayankhe. Komanso, odwala omwe ali ndi TRD ndi CRP yapamwamba adayankha bwino ku TNF? antagonist infliximab kuposa omwe ali ndi milingo yokhazikika.1
Pamodzi, umboni umasonyeza kuti ngakhale poyang'anira zinthu monga body mass index (BMI) ndi zaka, mayankho otupa amawoneka molakwika pafupifupi gawo limodzi mwa magawo atatu a odwala omwe ali ndi vuto la maganizo.55,56 Njira yotupa, komabe, ndi yovuta kwambiri, ndipo pali ma biomarkers ambiri omwe akuyimira mbali zosiyanasiyana zadongosolo lino. Posachedwapa, mabuku owonjezera a ma cytokines ndi ma chemokines apereka umboni wa zovuta za kupsinjika maganizo. Izi zikuphatikizapo: macrophage inhibitory protein 1a, IL-1a, IL-7, IL-12p70, IL-13, IL-15, eotaxin, granulocyte macrophage colony-stimulating factor,57 IL-5,58 IL-16,59 IL- 17,60 monocyte chemoattractant protein-4,61 thymus and activation-regulated chemokine,62 eotaxin-3, TNFb,63 interferon gamma-induced protein 10,64 serum amyloid A,65 soluble intracellular adhesion molecule66 and soluble vascular cell adhesion 1.67 cell adhesion.
Zotsatira za Growth Factor mu Depression
Poganizira za kufunikira kwa zinthu zomwe sizili za neurotrophic kukula (monga zomwe zimagwirizana ndi angiogenesis), timatchula za neuroogenic biomarkers pansi pa kutanthauzira kwakukulu kwa zinthu zakukula.
Brain-derived neurotrophic factor (BDNF) ndi yomwe imawerengedwa pafupipafupi mwa izi. Kusanthula kangapo kwa meta kumawonetsa kuchepetsedwa kwa mapuloteni a BDNF mu seramu, omwe amawoneka kuti akuwonjezeka pamodzi ndi mankhwala osokoneza bongo.68�71 Zomwe zaposachedwapa zafukufukuzi zikusonyeza kuti kusokonezeka kwa BDNF kumeneku kumawonekera kwambiri kwa odwala omwe ali ndi vuto lalikulu, koma kuti antidepressants amawoneka onjezerani miyeso ya puloteniyi ngakhale kuti palibe chithandizo chamankhwala.70 proBDNF yakhala ikuphunziridwa mocheperapo kusiyana ndi mawonekedwe okhwima a BDNF, koma awiriwa amawoneka kuti amasiyana mosiyana ndi ntchito (mogwirizana ndi zotsatira zawo pa tyrosine receptor kinase B receptors) ndi posachedwapa. umboni umasonyeza kuti ngakhale BDNF wokhwima akhoza kuchepetsedwa mu kuvutika maganizo, proBDNF ikhoza kuchulukitsidwa.72 Mitsempha ya kukula kwa mitsempha yomwe imayesedwa pamphepete mwa nyanja yanenedwanso kuti ndi yotsika kwambiri mu kuvutika maganizo kusiyana ndi kulamulira mu meta-analysis, koma sichingasinthidwe ndi mankhwala oletsa kuvutika maganizo ngakhale kuti ali otsika kwambiri. ochepetsedwa kwambiri mwa odwala omwe ali ndi vuto lalikulu la kuvutika maganizo.73 Zotsatira zofananazi zafotokozedwa mu meta-analysis kwa glial cell.mzere-derived neurotrophic factor.74
Vascular endothelial growth factor (VEGF) imathandizira kulimbikitsa angiogenesis ndi neurogenesis pamodzi ndi anthu ena a m'banja la VEGF (mwachitsanzo, VEGF-C, VEGF-D) ndipo ali ndi lonjezo la kuvutika maganizo.75 Ngakhale kuti pali umboni wosagwirizana, ma meta-analysis awiri ali ndi chiyembekezo. posachedwapa anasonyeza kukwera kwa VEGF m'magazi a odwala ovutika maganizo poyerekeza ndi zowongolera (kudutsa maphunziro a 16; P <0.001) .76,77 Komabe, VEGF yochepa yadziwika mu TRD78 ndipo magulu apamwamba adaneneratu kuti palibe chithandizo chamankhwala.79 Sizomveka. chifukwa chomwe mapuloteni a VEGF angakwezedwe, koma mwina amayamba chifukwa cha ntchito yotupa komanso/kapena kuwonjezeka kwa magazi�kulepheretsa ubongo kulowa m'malo ovutika maganizo omwe amayambitsa kuchepa kwa cerebrospinal fluid.80 Ubale pakati pa VEGF ndi kuyankha kwamankhwala sikudziwika bwino ; kafukufuku waposachedwapa sanapeze mgwirizano pakati pa VEGF ya seramu kapena BDNF ndi kuyankha kapena kuvutika maganizo, ngakhale kuchepa pamodzi ndi mankhwala osokoneza bongo. neurotrophic process.81 Basic fibroblast growth factor (kapena FGF-1) ndi membala wa fibroblast kukula factor factor ndipo amawoneka otsika kwambiri kuposa magulu olamulira.82,83 Komabe, malipoti samagwirizana; wina anapeza kuti puloteni iyi inali yochepa mu MDD kusiyana ndi kulamulira kwa thanzi labwino, koma inachepetsedwa mowonjezereka pamodzi ndi mankhwala oletsa kuvutika maganizo.2
Zina zokulirapo zomwe sizinafufuzidwe mokwanira pakuvutika maganizo zimaphatikizapo tyrosine kinase 2 ndi soluble fms-monga tyrosine kinase-1 (yotchedwanso sVEGFR-1) yomwe imagwirizana ndi VEGF, ndi tyrosine kinase receptors (yomwe imamanga BDNF) ikhoza kuchepetsedwa. mu kuvutika maganizo.86 Kukula kwa placenta kulinso gawo la banja la VEGF, koma silinaphunzire mu zitsanzo zowonongeka mwadongosolo kuti tidziwe.
Zotsatira za Metabolic Biomarker mu Kukhumudwa
Zizindikiro zazikulu zomwe zimagwirizanitsidwa ndi matenda a kagayidwe kachakudya zimaphatikizapo leptin, adiponectin, ghrelin, triglycerides, high-density lipoprotein (HDL), glucose, insulini ndi albumin.87 Mayanjano pakati pa ambiri mwa izi ndi kuvutika maganizo adawunikidwanso: leptin88 ndi ghrelin89 amawoneka otsika mu kuvutika maganizo. kuposa zowongolera m'mphepete mwake ndipo zitha kuchulukira limodzi ndi mankhwala ochepetsa nkhawa kapena kukhululukidwa. Kukana kwa insulini kungathe kuwonjezereka mu kuvutika maganizo, ngakhale pang'ono.90 Lipid profiles, kuphatikizapo HDL-cholesterol, imawoneka yosinthidwa kwa odwala ambiri omwe ali ndi vuto la kuvutika maganizo, kuphatikizapo omwe alibe matenda a comorbid, ngakhale kuti ubalewu ndi wovuta kwambiri ndipo umafunika kufotokozedwa.91 Kuwonjezera apo, hyperglycemia92 ndi hypoalbuminemia93 mu kukhumudwa zanenedwa mu ndemanga.
Kufufuza kwa madera onse a kagayidwe kachakudya kukuchulukirachulukira pogwiritsa ntchito mapanelo a metabolomics a mamolekyu ang'onoang'ono ndi chiyembekezo chopeza siginecha yolimba yamankhwala amisala. Pakafukufuku waposachedwapa pogwiritsa ntchito njira zopangira nzeru, ma metabolites omwe amasonyeza kuwonjezeka kwa glucose-lipid signing anali wolosera kwambiri za matenda a MDD,94 kuthandizira maphunziro apitalo.95
Zotsatira za Neurotransmitter mu Kukhumudwa
Ngakhale chidwi choperekedwa kwa ma monoamines mu kukhumudwa kwapereka chithandizo chopambana, palibe zolembera zolimba za neurotransmitter zomwe zadziwika kuti zithandizire kukulitsa chithandizo potengera kusankha kwa zolinga za monoamine za antidepressants. Ntchito zaposachedwa zikuwonetsa serotonin (5-hydroxytryptamine) 1A receptor yomwe ingakhale yofunikira pa matenda onse ndi chidziwitso cha kuvutika maganizo, poyembekezera njira zatsopano za chibadwa ndi zojambula.96 Pali mankhwala atsopano omwe angathe kutsata 5-hydroxytryptamine; mwachitsanzo, kugwiritsa ntchito kayendetsedwe kake ka 5-hydroxytryptophan.97 Kuwonjezeka kwa kufalikira kwa dopamine kumagwirizana ndi ma neurotransmitters ena kuti apititse patsogolo zotsatira za chidziwitso monga kupanga zisankho ndi kulimbikitsana.98 Mofananamo, neurotransmitters glutamate, noradrenaline, histamine ndi serotonin zingagwirizane ndi kuyambitsa. monga gawo la kupsinjika maganizo kokhudzana ndi kupsinjika maganizo; izi zitha kuchepetsa kupanga kwa 5-hydroxytryptamine kudzera �kusefukira�. Ndemanga yaposachedwa ikufotokoza chiphunzitsochi ndipo ikusonyeza kuti mu TRD, izi zikhoza kusinthidwa (ndi 5-HT kubwezeretsedwa) kupyolera mu chithandizo cha multimodal cholunjika ma neurotransmitters ambiri.99 Chochititsa chidwi n'chakuti, kuwonjezeka kwa serotonin sikumachitika nthawi zonse pamodzi ndi chithandizo chamankhwala chothandizira.100 Ngakhale izi , metabolites ya neurotransmitter monga 3-methoxy-4-hydroxyphenylglycol, ya noradrenaline, kapena homovanillic acid, ya dopamine, nthawi zambiri imapezeka kuti ikuwonjezeka pamodzi ndi kuchepetsa kuvutika maganizo ndi mankhwala ochepetsa kuvutika maganizo101,102 kapena kuti kuchepa kwa metabolites kumeneku kumaneneratu kuyankha kwabwinoko. Chithandizo cha SSRI.102,103
Zotsatira za Neuroendocrine mu Kukhumudwa
Cortisol ndiye chodziwika bwino kwambiri cha HPA axis biomarker yomwe idaphunziridwapo pakukhumudwa. Ndemanga zambiri zayang'ana pazowunikira zosiyanasiyana za ntchito za HPA; Zonsezi, izi zimasonyeza kuti kuvutika maganizo kumayenderana ndi hypercortisolemia komanso kuti cortisol kudzutsidwa kuyankha nthawi zambiri kumachepetsedwa.104,105 Izi zimathandizidwa ndi ndemanga yaposachedwa ya milingo ya cortisol yoyesedwa mu tsitsi, kuchirikiza lingaliro la cortisol hyperactivity mu kuvutika maganizo koma hypoactivity mu matenda ena monga monga vuto la mantha.106 Komanso, makamaka, milingo ya cortisol yokwezeka imatha kufotokozera kuyankha kovutirapo kwa psychological107 ndi antidepressant108 chithandizo. M'mbiri, chizindikiro chodalirika kwambiri cha neuroendocrine chomwe chikuyembekezeka kuyankhapo kwakhala kuyesa kwa dexamethasone, komwe kusakhazikika kwa cortisol pambuyo pa kuwongolera kwa dexamethasone kumalumikizidwa ndi mwayi wochepa wa chikhululukiro chotsatira. Komabe, chodabwitsa ichi sichinaganizidwe kuti n'chokwanira mokwanira kuti chigwiritsidwe ntchito kuchipatala. Zolemba zogwirizana ndi corticotrophin-release hormone ndi adrenocorticotropin hormone komanso vasopressin imapezeka mosagwirizana kuti imakhala yochuluka kwambiri mu kuvutika maganizo ndipo dehydroepiandrosterone imapezeka kuti imachepetsedwa; chiŵerengero cha cortisol ndi dehydroepiandrosterone chikhoza kukwezedwa ngati chizindikiro chokhazikika mu TRD, kupitirizabe pambuyo pa kukhululukidwa.109 Kusokonezeka kwa hormone ya Neuroendocrine kwa nthawi yaitali kumagwirizanitsidwa ndi kuvutika maganizo, ndipo hypothyroidism ingakhalenso ndi vuto la maganizo ovutika maganizo.110 Komanso, mayankho a chithokomiro amatha sinthani moyo ndi chithandizo chopambana cha kupsinjika maganizo.111
M'kati mwa pamwambapa, ndikofunikanso kulingalira njira zowonetsera machitidwe kudutsa machitidwe, monga glycogen synthase kinase-3, protein kinase ya mitogen-activated ndi cyclic adenosine 3?, 5?-monophosphate, yomwe imakhudzidwa ndi synaptic plasticity112 ndikusinthidwa ndi antidepressants.113 Komanso Ofuna kukhala ndi biomarker omwe amatengera machitidwe a biologic makamaka amayezedwa pogwiritsa ntchito neuroimaging kapena genetics. Poyankha kusowa kwa kusiyana kwakukulu komanso kofunikira kwa ma genomic pakati pa anthu omwe ali ndi nkhawa komanso osapsinjika, njira zamtundu wa 114 monga polygenic scores115 kapena telomere length116,117 zitha kukhala zothandiza kwambiri. Zowonjezera zodziwika bwino zomwe zikutchuka zikuwunika zozungulira kapena ma chronobiologic biomarkers pogwiritsa ntchito magwero osiyanasiyana. Actigraphy imatha kuwunika momwe kugona ndi kudzuka kumayendera ndikupumula kudzera pa accelerometer, ndipo zida za actigraphic zimatha kuyeza zinthu zina monga kuwala. Izi zikhoza kukhala zothandiza kwambiri pozindikira kusiyana ndi malipoti omwe amagwiritsidwa ntchito kawirikawiri a odwala ndipo angapereke zolosera zatsopano za kuyankhidwa kwa chithandizo.118 Funso lomwe ma biomarkers ndi omwe amalonjeza kwambiri kuti agwiritse ntchito kumasulira ndizovuta, zomwe zikukulitsidwa pansipa.
Zovuta Zamakono
Pazigawo zisanu za neurobiological zomwe zawunikiridwa, umboniwo umatsatira nkhani yofananira: pali ma biomarker ambiri omwe alipo omwe amalumikizidwa mwanjira zina ndi kupsinjika maganizo. Zolemba izi nthawi zambiri zimalumikizana movutikira, movuta kutengera chitsanzo. Umboniwu ndi wosagwirizana, ndipo zikutheka kuti ena ndi epiphenomena ya zinthu zina ndipo ena ndi ofunika m'magulu ochepa chabe a odwala. Ma biomarkers atha kukhala othandiza kudzera m'njira zosiyanasiyana (mwachitsanzo, omwe amalosera kuyankha kwamankhwala, omwe akuwonetsa kuti chithandizo chamankhwala chikuyenera kukhala chothandiza kwambiri kapena chomwe chimasintha ndikuchitapo kanthu mosasamala kanthu za kusintha kwachipatala). Njira zatsopano zimafunikira kukulitsa kusasinthika komanso kugwiritsiridwa ntchito kwachipatala pakuwunika kwa biologic m'magulu amisala.
Kusiyana kwa Biomarker
Kusiyanasiyana kwa ma biomarker pakapita nthawi komanso zochitika kumakhudza kwambiri mitundu ina (monga ma proteinomic) kuposa ena (genomics). Miyambo yokhazikika kwa ambiri kulibe kapena sikunavomerezedwe mofala. Zowonadi, chikoka cha zinthu zachilengedwe pa zolembera nthawi zambiri zimatengera chibadwa komanso kusiyana kwina kwa thupi pakati pa anthu omwe sangawerengedwe. Izi zimapangitsa kuwunika kwa zochitika za biomarker, ndikuzindikira zolakwika za biologic, kukhala kovuta kutanthauzira. Chifukwa cha kuchuluka kwa ma biomarkers, ambiri sanayesedwe mokulira kapena pagulu lathunthu pamodzi ndi zolembera zina zoyenera.
Zambiri zanenedwa kuti zikusintha kuchuluka kwa mapuloteni m'machitidwe a biologic mwa odwala omwe ali ndi vuto lokhudzidwa. Pamodzi ndi zinthu zokhudzana ndi kafukufuku monga nthawi yosungiramo zinthu (zomwe zingayambitse kuwonongeka kwa zinthu zina), izi zikuphatikizapo nthawi ya tsiku yoyezedwa, fuko, masewera olimbitsa thupi, zakudya za 119 (mwachitsanzo, zochitika za microbiome, makamaka ngati maphunziro ambiri a magazi a biomarker amachita. osafuna chitsanzo cha kusala kudya),120 kusuta fodya ndi kugwiritsa ntchito mankhwala osokoneza bongo,121 komanso zinthu za thanzi (monga comorbid kutupa, mtima kapena matenda ena akuthupi). Mwachitsanzo, ngakhale kuti kutupa kwakukulu kumawoneka mwa anthu ovutika maganizo koma omwe ali ndi thanzi labwino poyerekeza ndi magulu omwe sali ovutika maganizo, anthu ovutika maganizo omwe ali ndi matenda okhudzana ndi chitetezo cha mthupi nthawi zambiri amakhala ndi ma cytokines apamwamba kuposa omwe alibe kuvutika maganizo kapena matenda.122 Zinthu zina zodziwika bwino zotheka kutengapo gawo mu ubale pakati pa biomarkers, kukhumudwa ndi kuyankha kwamankhwala zafotokozedwa pansipa.
Kusokonezeka maganizo. Mayankho onse a endocrine ndi chitetezo chamthupi ali ndi maudindo odziwika bwino pakuyankha kupsinjika (zakuthupi kapena zamaganizidwe), komanso kupsinjika kwakanthawi panthawi yosonkhanitsira zitsanzo za biologic sikumayesedwa kawirikawiri m'maphunziro ofufuza ngakhale kusiyanasiyana kwa chinthu ichi pakati pa anthu omwe amatha kuchulukitsidwa ndi masiku ano. zizindikiro za maganizo. Kupsinjika maganizo kwakukulu komanso kosalekeza kumakhala ngati vuto la chitetezo cha mthupi, kulimbikitsa mayankho otupa m'kanthawi kochepa komanso kotalika. munthu wamkulu.123,124 Pa nthawi ya ubwana womvetsa chisoni, kutupa kwakukulu kunanenedwanso mwa ana omwe anali ovutika maganizo pakalipano.125,126 Mosiyana ndi zimenezi, anthu omwe ali ndi vuto la kuvutika maganizo komanso mbiri ya kuvulala kwaubwana akhoza kusokoneza mayankho a cortisol kupsinjika maganizo, poyerekeza ndi omwe ali ndi maganizo ovutika maganizo komanso ovutika maganizo. palibe kuvulala koyambirira kwa moyo.127 Kusintha kwa axis ya HPA yopanikizika kumawoneka yogwirizana ndi chidziwitso,128 komanso kupsinjika maganizo kapena kusiyana kwa majini okhudzana ndi HPA.129 Kupsinjika maganizo kumakhalanso ndi zotsatira zaufupi komanso zautali pa neurogenesis130 ndi mitsempha ina. Njira.131 Sizikudziwika bwino momwe kuvulala paubwana kumakhudzira zizindikiro zamoyo mwa munthu wamkulu wovutika maganizo. s, koma ndizotheka kuti kupsinjika kwakanthawi kochepa kumapangitsa anthu ena kupirira kupsinjika akakula komwe kumakulitsidwa m'malingaliro komanso/kapena mwachilengedwe.
Kugwira ntchito mwachidziwitso. Kusokonezeka kwa ubongo kumachitika kawirikawiri kwa anthu omwe ali ndi vuto lachidziwitso, ngakhale mu MDD.133 Kuperewera kwa chidziwitso kumawoneka kowonjezereka pamodzi ndi kukana chithandizo.134 Neurobiologically, HPA axis129 ndi neurotrophic systems135 zikhoza kukhala ndi gawo lalikulu pa chiyanjano. Neurotransmitters noradrenaline ndi dopamine ndizofunika kwambiri pazochitika zachidziwitso monga kuphunzira ndi kukumbukira.136 Mayankho okwera kwambiri otupa agwirizanitsidwa ndi kuchepa kwa chidziwitso, ndipo mwina amakhudza kugwira ntchito kwachidziwitso muzochitika zachisokonezo,137 ndi kukhululukidwa, kupyolera mu njira zosiyanasiyana.138 Zoonadi, Krogh et al139 adanena kuti CRP imagwirizana kwambiri ndi chidziwitso cha chidziwitso kusiyana ndi zizindikiro zazikulu za kuvutika maganizo.
Zaka, jenda ndi BMI. Kusakhalapo kapena kukhalapo, ndi malangizo a kusiyana kwa biologic pakati pa amuna ndi akazi kwakhala kosiyana kwambiri ndi umboni mpaka lero. Kusiyana kwa mahomoni a Neuroendocrine pakati pa amuna ndi akazi kumagwirizana ndi kuvutika maganizo.140 Kuwunika kwa kafukufuku wotupa kunanena kuti kulamulira kwa msinkhu ndi kugonana sikunakhudze kusiyana kwa kulamulira kwa odwala mu cytokines yotupa (ngakhale kuti mgwirizano pakati pa IL-6 ndi kuvutika maganizo unachepetsedwa pamene zaka zikuwonjezeka, zomwe zimagwirizana ndi malingaliro akuti kutupa nthawi zambiri kumakula ndi zaka) 41,141 VEGF kusiyana pakati pa odwala ndi maulamuliro ndi zazikulu mu maphunziro oyesa zitsanzo zazing'ono, pamene jenda, BMI ndi zochitika zachipatala sizinakhudze kufananitsa uku pamlingo wa meta-analytic.77 Komabe, kusowa kwa kusintha kwa BMI m'mayesero am'mbuyomu a kutupa ndi kuvutika maganizo kumawoneka kuti kusokoneza kusiyana kwakukulu komwe kunachitika pakati pa maguluwa.41 Minofu yowonjezereka ya adipose yasonyezedwa motsimikizika kuti imalimbikitsa kupanga cytokine komanso kugwirizana kwambiri ndi zizindikiro za kagayidwe kachakudya.142 Chifukwa mankhwala a psychotropic akhoza kugwirizana ndi wei ght phindu ndi BMI yapamwamba, ndipo izi zakhala zikugwirizana ndi kukana chithandizo mu kupsinjika maganizo, ili ndi gawo lofunikira loti mufufuze.
Mankhwala. Maphunziro ambiri a biomarker mu kupsinjika maganizo (onse apakati ndi aatali) asonkhanitsa zitsanzo zoyambira mwa omwe sanatengerepo mankhwala kuti achepetse kusiyanasiyana. Komabe, zambiri mwazowunikirazi zimatengedwa pakatha nthawi yotsuka kuchokera kumankhwala, zomwe zimasiya chinthu chomwe chingakhale chosokoneza kwambiri cha kusintha kotsalira kwa physiology, kukulitsidwa ndi mitundu yambiri yamankhwala omwe angakhalepo omwe angakhale ndi zotsatira zosiyana pa kutupa. Maphunziro ena sanaphatikizepo psychotropic, koma osati mankhwala ena ogwiritsira ntchito: makamaka, mapiritsi oletsa kubereka amaloledwa kawirikawiri kwa ochita kafukufuku ndipo samayang'aniridwa muzofufuza, zomwe zasonyezedwa posachedwapa kuti ziwonjezere kuchuluka kwa mahomoni ndi cytokine.143,144 Kafukufuku wambiri amasonyeza kuti antidepressant mankhwala amakhudza kuyankha kwa kutupa,34,43,49,145�147 HPA-axis,108 neurotransmitter,148 ndi neurotrophic149 ntchito. Komabe, mankhwala ambiri omwe angakhalepo okhudza kuvutika maganizo ali ndi zosiyana komanso zovuta za pharmacologic, zomwe zimasonyeza kuti pakhoza kukhala zotsatira za biologic zamitundu yosiyanasiyana ya chithandizo, mothandizidwa ndi zomwe zilipo panopa. Zakhala zikudziwika kuti kuwonjezera pa zotsatira za monoamine, mankhwala enieni a serotonin (ie, SSRIs) amatha kutsata kusintha kwa Th2 mu kutupa, ndi noradrenergic antidepressants (mwachitsanzo, SNRIs) zimakhudza kusintha kwa Th1 Sizinatheka kudziwa zotsatira za mankhwala pawokha kapena ophatikiza pa biomarkers. Izi mwina zimalumikizidwa ndi zinthu zina kuphatikiza kutalika kwa chithandizo (mayesero ochepa amawunika kugwiritsa ntchito mankhwala kwanthawi yayitali), zitsanzo zamitundu yosiyanasiyana komanso osasokoneza omwe akutenga nawo gawo poyankha chithandizo.
Zosiyanasiyana
Njira. Monga tafotokozera pamwambapa, kusiyana (pakati ndi mkati mwa maphunziro) ponena za mankhwala (ndi zosakaniza) zomwe otenga nawo mbali akutenga ndipo adatenga kale ziyenera kuwonetsa kusiyanasiyana muzofukufuku, makamaka mu kafukufuku wa biomarker. Kuphatikiza pa izi, mapangidwe ena ambiri ndi mawonekedwe a zitsanzo amasiyana m'maphunziro onse, motero zimakulitsa zovuta pakutanthauzira ndikuwonetsa zomwe zapezedwa. Izi zikuphatikiza magawo oyezera ma biomarker (mwachitsanzo, zida zoyeserera) ndi njira zopezera, kusunga, kukonza ndi kusanthula zolembera mu kupsinjika maganizo. Hiles et al141 adasanthula magwero ena osagwirizana m'mabuku okhudzana ndi kutupa ndipo adapeza kuti kulondola kwa matenda ovutika maganizo, BMI ndi matenda a comorbid ndizofunikira kwambiri pakuwunika kutupa kwapakati pakati pamagulu ovutika maganizo ndi osapsinjika.
Zachipatala. Kusiyanasiyana kwakukulu kwa anthu ovutika maganizo kumalembedwa bwino151 ndipo ndizothandiza kwambiri pakusiyanitsa zofukufuku m'mabuku ofufuza. Ndizotheka kuti ngakhale mkati mwa matenda, mbiri yosadziwika bwino ya biologic imangokhala m'magulu a anthu omwe sangakhale okhazikika pakapita nthawi. Magulu ang'onoang'ono a anthu omwe akuvutika ndi kupsinjika maganizo amatha kudziwika kudzera mumgwirizano wamaganizo ndi biologic. Pansipa, tikuwonetsa kuthekera kofufuza timagulu tating'ono kuti tithane ndi zovuta zomwe kusinthika kwa biomarker ndi heterogeneity kumabweretsa.
Subtypes mkati mwa Depression
Mpaka pano, palibe magulu ang'onoang'ono omwe ali m'magulu ang'onoang'ono omwe ali m'magulu ovutika maganizo kapena ovutika maganizo omwe amatha kusiyanitsa pakati pa odwala pogwiritsa ntchito zizindikiro kapena kuyankhidwa kwa mankhwala. zitha kuyambitsa njira yopita ku chithandizo cha stratified. Kunugi et al152 aperekanso magawo anayi omwe atha kutengera gawo la machitidwe osiyanasiyana a neurobiological omwe amawonetsa ma subtypes okhudzana ndi kupsinjika: omwe ali ndi hypercortisolism yowonetsa kupsinjika kwa melancholic, kapena hypocortisolism yowonetsa subtype ya atypical, gawo lokhudzana ndi dopamine la odwala omwe amatha. kupezeka kwambiri ndi anhedonia (ndipo amatha kuyankha bwino, mwachitsanzo, aripiprazole) ndi gawo lotupa lomwe limadziwika ndi kutupa kwakukulu. Nkhani zambiri zokhudzana ndi kutupa zafotokoza za kukhalapo kwa "inflammatory subtype". Zanenedwa kuti anthu omwe ali ndi vuto la kuvutika maganizo atha kukhala ndi kutupa kwakukulu kusiyana ndi melancholic subtype,153 yomwe mwina sikugwirizana ndi zomwe zapeza zokhudza HPA axis mu melancholic ndi atypical subtypes of depression. TRD55,56,154,155 kapena kuvutika maganizo komwe kuli ndi zizindikiro zodziwika bwino za somatic156 kwatchulidwanso ngati njira yotupa, koma neurovegetative (kugona, chilakolako, kutaya libido), maganizo (kuphatikizapo kukhumudwa, kudzipha ndi kukwiya) ndi zizindikiro zamaganizo (kuphatikizapo kukondera komanso kudziimba mlandu) 37 onse kuwoneka okhudzana ndi mbiri yazachilengedwe. Enanso omwe angakhale okhudzidwa ndi kagawo kakang'ono ka kutupa kumaphatikizapo zochitika za matenda monga zizindikiro157 kapena metabolic syndrome.158
Kutengera (hypo) mania kumatha kusiyanitsa mwachilengedwe pakati pa odwala omwe akuvutika maganizo. Umboni tsopano ukusonyeza kuti matenda ochititsa munthu kusinthasintha zochitika ndi gulu la mitundu yambiri ya matenda a maganizo, omwe ali ndi vuto la bipolar subsyndromal lomwe limapezeka kwambiri kuposa lomwe linazindikiridwa kale. nthawi yapakati yokonza matenda nthawi zambiri imadutsa zaka 161 ndipo kuchedwa kumeneku kumayambitsa kuopsa kwakukulu ndi mtengo wa matenda onse.162 Ndi odwala ambiri omwe ali ndi matenda ochititsa munthu kusinthasintha maganizo omwe amayamba ndi matenda amodzi kapena angapo ovutika maganizo ndi kuvutika maganizo kwa unipolar kukhala vuto lolakwika kwambiri, kuzindikira Zinthu zomwe zingasiyanitse pakati pa kuvutika maganizo kwa unipolar ndi bipolar zimakhala ndi zotsatira zazikulu.163 Matenda a bipolar spectrum mwina sanawonekere mu kafukufuku wina wam'mbuyo wa MDD biomarker, ndipo kusweka kwa umboni kumasonyeza kusiyana kwa ntchito ya HPA axis164 kapena kutupa109 pakati pa bipolar ndi unipolar depr. gawo. Komabe, mafananidwe awa ndi osowa, amakhala ndi zitsanzo zazing'ono, zodziwika zosafunikira zomwe zimachitika kapena anthu olembedwa omwe sanadziwike bwino ndi matenda. Kufufuza uku sikuwunikanso gawo la kuyankha kwamankhwala mu maubwenzi awa.
Matenda onse a bipolar167 ndi kukana chithandizo168 sizomangamanga ndipo amagona pa continua, zomwe zimawonjezera vuto la chizindikiritso cha subtype. Kupatula pa subtyping, ndikofunikira kudziwa kuti zovuta zambiri za biologic zomwe zimawonedwa pakuvutika maganizo zimapezekanso mwa odwala omwe ali ndi matenda ena. Chifukwa chake, mayeso a transdiagnostic nawonso ndiwofunikira.
Zovuta za Kuyeza kwa Biomarker
Kusankhidwa kwa Biomarker. Kuchuluka kwa ma biomarker omwe angakhale othandiza kumapereka zovuta kwa psychobiology pozindikira kuti ndi zolembera ziti zomwe zimakhudzidwa ndi njira iti komanso kwa ndani. Kuti achulukitse vutoli, owerengeka ochepa mwa anthu omwe ali ndi matendawa adafufuzidwa mokwanira pakukhumudwa, ndipo kwa ambiri, maudindo awo omwe ali ndi thanzi labwino komanso azachipatala samveka bwino. Ngakhale izi, kuyesayesa kangapo kwapangidwa kuti apereke malingaliro olonjeza mapanelo a biomarker. Kuphatikiza pa Brand et al's 16 ya zolembera zokhala ndi kuthekera kolimba,27 Lopresti et al akufotokozeranso zowonjezera zowonjezera zolembera za okosijeni zomwe zimatha kuwongolera kuyankha kwamankhwala. biologic systems (BDNF, cortisol, soluble TNF? receptor type II, alpha28 antitrypsin, apolipoprotein CIII, epidermal growth factor, myeloperoxidase, prolactin ndi resistin) muzitsulo zovomerezeka ndi zobwerezabwereza ndi MDD. Kamodzi pamodzi, muyeso wamagulu a maguluwa unatha kusiyanitsa pakati pa MDD ndi magulu olamulira omwe ali ndi 1%�80% molondola.90 Tikukulimbikitsani kuti ngakhale izi sizikuphimba onse omwe angakhale nawo pa ntchitoyi; onani Table 169 kuti mufotokoze mozama za ma biomarkers omwe angathe kukhumudwa, omwe ali ndi zonse zomwe zili ndi umboni komanso zolembera zatsopano.
Zamakono. Chifukwa cha kupita patsogolo kwaukadaulo, tsopano ndi kotheka (zowonadi, zosavuta) kuyeza mitundu yayikulu ya ma biomarker munthawi imodzi pamtengo wotsika komanso wokhudzidwa kwambiri kuposa momwe zimakhalira kale. Pakalipano, kuthekera uku kuyeza mankhwala ambiri kuli patsogolo pa kuthekera kwathu kusanthula bwino ndikutanthauzira deta,170 chinachake chomwe chidzapitirira ndi kukwera kwa biomarker arrays ndi zizindikiro zatsopano monga ndi metabolomics. Izi zimachitika makamaka chifukwa chosamvetsetsa bwino za udindo ndi maubale pakati pa zolembera, komanso kusamvetsetsa bwino momwe zolembera zimalumikizirana ndi magawo osiyanasiyana achilengedwe (monga majini, zolemba, zomanga thupi) mkati ndi pakati pa anthu. Deta yayikulu yogwiritsira ntchito njira zatsopano zowunikira ndi miyezo ithandizira kuthana ndi izi, ndipo njira zatsopano zikuperekedwa; Chitsanzo chimodzi ndi chitukuko cha njira zowerengera zomwe zimakhazikitsidwa ndi kusanthula kosinthika kuti apeze zizindikiro zatsopano za kagayidwe kachakudya kutengera momwe amachitira pakati pa maukonde ndikuphatikiza ma jini ndi data ya metabolite.171 Njira zophunzirira makina zikugwiritsidwa ntchito kale ndipo zithandizira ndi zitsanzo zogwiritsa ntchito biomarker. deta kuti iwonetsere zotsatira za chithandizo mu maphunziro ndi deta yaikulu.172
Kuphatikiza ma biomarkers. Kuwunika ma biomarker angapo nthawi imodzi ndi njira ina yoyang'anira zolembera zapaokha zomwe zingapereke malingaliro olondola mu intaneti yovuta ya biologic systems kapena network. ndipo kuyanjana kumamveka bwino), deta ya biomarker imatha kuphatikizidwa kapena kulembedwa. Vuto limodzi ndikuzindikira njira yabwino yochitira izi, ndipo kungafunike kuwongolera kwaukadaulo ndi/kapena njira zowunikira zatsopano (onani gawo la �Data Yazikulu). Zakale, ziwerengero pakati pa zizindikiro ziwiri zosiyana zamoyo zapeza zotsatira zosangalatsa.26 Zoyesera zochepa zapangidwa kuti ziphatikize deta ya biomarker pamlingo wokulirapo, monga omwe amagwiritsa ntchito chigawo chachikulu cha proinflammatory cytokine networks.109,173 Mu meta-analysis, proinflammatory cytokines yakhala ikugwiritsidwa ntchito. kusinthidwa kukhala chiŵerengero cha kukula kwachinthu chimodzi pa phunziro lirilonse, ndipo chonsecho chinasonyeza kutupa kwakukulu kwambiri musanayambe chithandizo cha antidepressant, kuneneratu kusayankhidwa kotsatira mu maphunziro a odwala kunja. Mapulogalamu ophatikizika a biomarker ndizovuta komanso mwayi wofufuza zam'tsogolo kuti azindikire zopeza zomveka komanso zodalirika zomwe zingagwiritsidwe ntchito popititsa patsogolo zotsatira za chithandizo.174 Kafukufuku wa Papakostas et al adatenga njira ina, posankha gulu la serum biomarkers (ya kutupa), HPA axis and metabolic systems) zomwe zinasonyezedwa kuti zimasiyana pakati pa anthu ovutika maganizo ndi olamulira mu phunziro lapitalo ndipo adazipanga izi kukhala chiopsezo chosiyana ndi zitsanzo ziwiri zodziimira ndi gulu lolamulira ndi> 43% sensitivity ndi specificity.80
Deta yaikulu. Kugwiritsiridwa ntchito kwa deta yaikulu kungakhale kofunikira pothana ndi zovuta zomwe zilipo panopa zozungulira kusiyanasiyana, kusiyana kwa biomarker, kuzindikira zolembera zoyenera ndikubweretsa gawolo kumasulira, kufufuza kogwiritsidwa ntchito mu kuvutika maganizo. Komabe, monga tafotokozera pamwambapa, izi zimabweretsa zovuta zamakono ndi sayansi.175 Sayansi ya zaumoyo yangoyamba kumene kugwiritsa ntchito ma analytics akuluakulu a deta, zaka khumi kapena kuposerapo kusiyana ndi gawo lazamalonda. Komabe, maphunziro monga iSPOT-D152 ndi consortia monga Psychiatric Genetics Consortium176 akupita patsogolo ndi kumvetsetsa kwathu kwa biologic njira mu psychiatry. Ma algorithms ophunzirira makina, m'mafukufuku ochepa kwambiri, adayamba kugwiritsidwa ntchito ku zolembera za kupsinjika maganizo: kafukufuku waposachedwapa adasonkhanitsa deta kuchokera ku> 5,000 otsogolera a 250 biomarkers; pambuyo potengera kangapo kwa data, kuphunzira kwa makina kumachulukira kunachitika, kuwonetsa 21 zomwe zingapangitse biomarker. Kutsatira kuwunika kowonjezereka, zozindikiritsira zitatu zidasankhidwa kuti zigwirizane kwambiri ndi zizindikiro zakukhumudwa (kukula kwa maselo ofiira ofiira, kuchuluka kwa shuga m'magazi ndi bilirubin). Olembawo amanena kuti deta yaikulu ingagwiritsidwe ntchito bwino popanga malingaliro.177 Ntchito zazikulu za biomarker phenotyping zikuyenda tsopano ndipo zidzathandiza kupititsa patsogolo ulendo wathu ku tsogolo la neurobiology of depression.
Tsogolo Labwino
Chizindikiritso cha Gulu la Biomarker
Zomwe zapezeka m'mabuku mpaka pano zimafuna kubwerezabwereza m'maphunziro akuluakulu. Izi ndizowona makamaka kwa zolemba zakale, monga chemokine thymus ndi activation-regulated chemokine ndi kukula kwa tyrosine kinase 2 zomwe, malinga ndi chidziwitso chathu, sizinafufuzidwe mu zitsanzo zowongolera odwala omwe ali ndi nkhawa komanso athanzi. Maphunziro akulu azidziwitso amayenera kuyesa mapanelo athunthu a biomarker ndikugwiritsa ntchito njira zowunikira zapamwamba kuti atsimikizire bwino mgwirizano pakati pa zolembera ndi zinthu zomwe zimawasintha m'magulu azachipatala komanso omwe siachipatala. Kuphatikiza apo, kubwereza kwakukulu kwa kusanthula kwazinthu zazikulu kumatha kukhazikitsa magulu olumikizana kwambiri a biomarkers komanso kutha kudziwitsanso kugwiritsa ntchito "composites" mu biologic psychiatry, zomwe zingapangitse kusiyanasiyana kwa zomwe zapezedwa mtsogolo.
Kupezeka kwa Homogenous Subtypes
Pankhani ya kusankha kwa biomarker, mapanelo angapo angafunike panjira zosiyanasiyana zomwe kafukufuku angakhudze. Kuphatikizidwa pamodzi, umboni waposachedwa ukuwonetsa kuti mbiri ya biomarker ndiyotsimikizika, koma imasinthidwa mosadukiza m'gulu la anthu omwe akuvutika ndi kukhumudwa. Izi zitha kukhazikitsidwa mkati kapena m'magulu onse ozindikira matenda, zomwe zingayambitse kusagwirizana kwa zomwe zapezedwa m'mabuku awa. Kuwerengera gulu lazachilengedwe (kapena magulu ang'onoang'ono) kumatha kuthandizidwa bwino ndi kusanthula kwakukulu kwamagulu amtundu wa biomarker network mu kukhumudwa. Izi zitha kuwonetsa kusiyanasiyana kwa anthu; kusanthula kwa m'kalasi kobisika kumatha kuwonetsa mawonekedwe apadera azachipatala kutengera, mwachitsanzo, kutupa.
Zotsatira Zachidziwitso Zachindunji pa Kutupa ndi Kuyankha
Mankhwala onse omwe amaperekedwa nthawi zambiri a kupsinjika maganizo ayenera kuunika mozama za zotsatira zake za biologic, komanso kuwerengera mphamvu ya mayesero a chithandizo. Izi zitha kupangitsa kuti mapangidwe okhudzana ndi ma biomarkers ndi mawonetsedwe azizindikiro kuti athe kuneneratu zotsatira zamankhwala osiyanasiyana odetsa nkhawa m'njira yokhazikika, ndipo zitha kukhala zotheka malinga ndi kupsinjika kwa unipolar ndi bipolar. Izi zitha kukhala zothandiza pazamankhwala omwe angotsala pang'ono kutha komanso machiritso omwe awonetsedwa pano.
Chidziwitso Choyembekezeka cha Kuyankha kwa Chithandizo
Kugwiritsa ntchito njira zomwe zili pamwambazi zitha kupangitsa luso lolosera za kukana chithandizo. Zowona komanso zolimbikira (mwachitsanzo, zanthawi yayitali) zoyankhira chithandizo zitha kuthandizira izi. Kuwunika kwa njira zina zovomerezeka zaukhondo wa odwala (monga moyo wabwino ndi magwiridwe antchito a tsiku ndi tsiku) kungapereke kuwunika kokwanira kwa zotsatira zamankhwala zomwe zingagwirizane kwambiri ndi zolembera. Ngakhale kuti zochitika zamoyo zokha sizingathe kusiyanitsa oyankha chithandizo kuchokera kwa omwe sanayankhe, kuyeza kwa nthawi imodzi kwa zizindikiro zamoyo zomwe zimakhala ndi maganizo kapena chiwerengero cha anthu zitha kuphatikizidwa ndi chidziwitso cha biomarker popanga chitsanzo cholosera cha kuyankha kosakwanira kwa chithandizo. Ngati chitsanzo chodalirika chapangidwa kuti chilosere kuyankha (mwina kwa anthu ovutika maganizo kapena chiwerengero cha anthu ochepa) ndikutsimikiziridwa mobwerezabwereza, kamangidwe kake kamasuliridwe kamene kamatha kutsimikizira kugwiritsidwa ntchito kwake muyeso lalikulu lolamulidwa.
Kukonzekera kwa Stratified Treatments
Pakalipano, odwala omwe ali ndi vuto la kuvutika maganizo samalangizidwa mwadongosolo kuti alandire pulogalamu yabwino yothandizira. Ngati zitsimikiziridwa, mapangidwe oyesera a stratified angagwiritsidwe ntchito kuyesa chitsanzo kuti adziwiretu kusayankhidwa ndi / kapena kudziwa komwe wodwala akuyenera kuyesedwa mu chitsanzo chothandizira. Izi zitha kukhala zothandiza pazamankhwala okhazikika komanso achilengedwe, m'njira zosiyanasiyana. Pamapeto pake, chitsanzo chotheka kupangidwa kuti chipatse anthu chithandizo choyenera kwambiri, kuti azindikire omwe ali ndi vuto la kuvutika maganizo komanso kupereka chisamaliro ndi kuwunika kwa odwalawa. Odwala omwe amadziwika kuti ali pachiwopsezo chokana kulandira chithandizo akhoza kupatsidwa chithandizo chamankhwala chophatikizana chamalingaliro ndi pharmacologic kapena kuphatikiza pharmacotherapy. Monga chitsanzo chongopeka, otenga nawo mbali omwe alibe proinflammatory cytokine kukwera angasonyezedwe kuti amalandira chithandizo chamaganizo m'malo mwa pharmacologic, pamene kagawo kakang'ono ka odwala omwe ali ndi kutupa kwakukulu amatha kulandira anti-inflammatory agent pakuwonjezera chithandizo chamankhwala. Mofanana ndi stratification, njira zosankhidwa payekha payekha zingatheke m'tsogolomu. Mwachitsanzo, munthu wina wovutika maganizo angakhale ndi TNF yapamwamba kwambiri? milingo, koma palibe zovuta zina zamoyo, ndipo angapindule ndi chithandizo chanthawi yayitali ndi TNF? antagonist.54 Chithandizo chamunthu payekha chingaphatikizeponso kuyang'anira mawonekedwe a biomarker panthawi ya chithandizo kuti adziwitse kusintha komwe kungachitike, kutalika kwa chithandizo chopitilira chofunikira kapena kuzindikira zizindikiro zoyambilira za kubwereranso.
Zolinga Zamankhwala Zatsopano
Pali chithandizo chambiri chomwe chingakhale chothandiza pakukhumudwa, chomwe sichinawunikidwe mokwanira, kuphatikiza njira zaposachedwa kapena zobwezeredwa kuchokera kumaphunziro ena azachipatala. Zina mwazolinga zodziwika bwino zakhala mu mankhwala oletsa kutupa monga celecoxib (ndi zina za cyclooxygenase-2 inhibitors), TNF? antagonists etanercept ndi infliximab, minocycline kapena aspirin. Izi zimawoneka zolimbikitsa.178 Mankhwala a Antiglucocorticoid, kuphatikizapo ketoconazole179 ndi metyrapone,180 afufuzidwa chifukwa cha kuvutika maganizo, koma onsewa ali ndi zovuta zokhudzana ndi zotsatira zake ndipo mphamvu yachipatala ya metyrapone ndi yosatsimikizika. Mifepristone181 ndi corticosteroids fludrocortisone ndi spironolactone,182 ndi dexamethasone ndi hydrocortisone183 zingakhalenso zothandiza pochiza kuvutika maganizo kwa nthawi yochepa. Kulimbana ndi glutamate N-methyl-d-aspartate receptor antagonists, kuphatikizapo ketamine, akhoza kuyimira chithandizo chamankhwala chogwira mtima mu maganizo. kukhala ndi zotsatira za antidepressant184 kudzera mu njira zoyenera za neurobiological pathways.3
Mwa njira iyi, zotsatira za biochemical za antidepressants (onani �Medication� gawo) zakhala zikugwiritsidwa ntchito kuti zipindule zachipatala m'magulu ena: makamaka matenda a gastroenterological, neurologic ndi osadziwika bwino. zopindulitsa izi. Lithium yaperekedwanso kuti ichepetse kutupa, mozama kwambiri kudzera mu njira za glycogen synthase kinase-188 Kuganizira kwambiri za zotsatirazi kungakhale kothandiza pa siginecha ya kupsinjika maganizo, ndipo, zizindikiro zowonongeka zikhoza kuyimira zizindikiro za chitukuko chatsopano cha mankhwala.
Kuzindikira kwa Dr. Alex Jimenez
Kukhumudwa ndi vuto la thanzi laubongo lomwe limadziwika ndi zizindikiro zazikulu zomwe zimakhudza momwe munthu akumvera, kuphatikizapo kutaya chidwi ndi zochita. Komabe, kafukufuku waposachedwapa wapeza kuti n’zotheka kuzindikira kuvutika maganizo pogwiritsa ntchito zambiri osati chabe zizindikiro za khalidwe la wodwala. Malinga ndi ofufuzawo, kuzindikira zozindikiritsa zopezeka mosavuta zomwe zitha kuzindikiritsa kukhumudwa ndikofunikira kwambiri pakuwongolera thanzi ndi thanzi la wodwala. Mwachitsanzo, zomwe zapezeka m'chipatala zimasonyeza kuti anthu omwe ali ndi vuto lalikulu lachisokonezo, kapena MDD, ali ndi mamolekyu ochepa acetyl-L-carnitine, kapena LAC, m'magazi awo kuposa momwe amachitira bwino. Pamapeto pake, kukhazikitsa ma biomarkers a kupsinjika kungathandize kudziwa yemwe ali pachiwopsezo chotenga matendawa komanso kuthandiza akatswiri azachipatala kudziwa njira yabwino yothandizira odwala omwe ali ndi vuto la kukhumudwa.
Kutsiliza
Mabukuwo akuwonetsa kuti pafupifupi magawo awiri mwa atatu a odwala omwe ali ndi vuto la kuvutika maganizo samapeza chikhululukiro ku chithandizo choyambirira komanso kuti mwayi wosayankhidwa ukuwonjezeka ndi chiwerengero cha mankhwala omwe ayesedwa. Kupereka chithandizo chamankhwala chosagwira ntchito kumakhala ndi zotsatirapo zazikulu pamtengo wamunthu payekha komanso chikhalidwe cha anthu, kuphatikiza kupsinjika kosalekeza komanso kusakhala bwino, chiopsezo chodzipha, kutayika kwa zokolola komanso kuwonongeka kwazinthu zothandizira zaumoyo. Zolemba zambiri zakukhumudwa zikuwonetsa kuchuluka kwa ma biomarkers omwe angathe kupititsa patsogolo chithandizo kwa anthu omwe ali ndi vuto la kuvutika maganizo. Kuphatikiza pa zolembera za neurotransmitter ndi neuroendocrine zomwe zakhala zikufufuzidwa kwazaka zambiri, zidziwitso zaposachedwa zikuwonetsa kuyankha kwa kutupa (ndi chitetezo chamthupi nthawi zambiri), kagayidwe kachakudya ndi kukula komwe kumakhudzidwa kwambiri ndi kukhumudwa. Komabe, umboni wosiyana kwambiri ukuwonetsa kuti pali zovuta zingapo zomwe ziyenera kuthetsedwa musanagwiritse ntchito kafukufuku wa biomarker kuti apititse patsogolo kasamalidwe ndi chisamaliro cha anthu omwe akuvutika maganizo. Chifukwa cha kuchulukirachulukira kwa machitidwe a biologic, kuyezetsa nthawi imodzi kwa zolembera zodzaza mu zitsanzo zazikulu kumakhala kopindulitsa kwambiri pozindikira kuyanjana pakati pa biologic ndi psychological state pamunthu payekhapayekha. Kuwongolera muyeso wa magawo onse a neurobiological komanso njira zakuchipatala zakukhumudwa ndikothekera kupangitsa kumvetsetsa kwakukulu. Ndemangayi ikuwonetsanso kufunikira kowunika zinthu zomwe zingasinthe (monga matenda, zaka, kuzindikira ndi mankhwala) kuti tipeze kumvetsetsa kogwirizana kwa biology ya kupsinjika maganizo ndi njira zopewera chithandizo. N'kutheka kuti zolembera zina zidzasonyeza kulonjeza kwachipatala kapena kukana chithandizo chamankhwala m'magulu ang'onoang'ono a odwala, ndipo kuyesa kofanana kwa chidziwitso cha biologic ndi maganizo kungathandize kuti athe kuzindikira omwe ali pachiopsezo cha zotsatira zoipa za chithandizo. Kukhazikitsa gulu la biomarker kumakhudzanso kulimbikitsa kulondola kwa matenda ndi kuneneratu, komanso kudzipangira payekhapayekha chithandizo cha matenda okhumudwa ndikukhazikitsa zolinga zabwino zachipatala. Zotsatirazi zitha kungokhala m'magulu ang'onoang'ono a odwala omwe akuvutika maganizo. Njira zopezera zothekazi zimathandizira njira zofufuzira zaposachedwa kuti zigwirizane ndi ma syndromes azachipatala mozama kwambiri ndi ma substrates a neurobiological.6 Kupatula kuchepetsa kusiyanasiyana, izi zitha kuthandizira kusintha kwa kulemekezana pakati pa thanzi lakuthupi ndi lamalingaliro. Zikuwonekeratu kuti ngakhale ntchito yochuluka ikufunika, kukhazikitsidwa kwa ubale pakati pa ma biomarkers oyenerera ndi matenda ovutika maganizo kuli ndi zotsatira zazikulu zochepetsera kupsinjika maganizo pamunthu payekha komanso pagulu.
Kuvomereza
Lipotili likuyimira kafukufuku wodziyimira pawokha wothandizidwa ndi National Institute for Health Research (NIHR) Biomedical Research Center ku South London ndi Maudsley NHS Foundation Trust ndi King's College London. Malingaliro omwe afotokozedwa ndi a olemba osati a NHS, NIHR kapena Dipatimenti ya Zaumoyo.
Mawu a M'munsi
Kuwulula. AHY ali m'zaka zapitazi za 3 adalandira ulemu chifukwa cholankhula kuchokera ku Astra Zeneca (AZ), Lundbeck, Eli Lilly, Sunovion; honoraria pofunsira kuchokera kwa Allergan, Livanova ndi Lundbeck, Sunovion, Janssen; ndi thandizo la ndalama zofufuzira kuchokera ku Janssen ndi mabungwe opereka ndalama ku UK (NIHR, MRC, Wellcome Trust). AJC m'zaka zapitazi za 3 yalandira ulemu chifukwa cholankhula kuchokera ku Astra Zeneca (AZ), ulemu chifukwa cha uphungu kuchokera kwa Allergan, Livanova ndi Lundbeck, ndi thandizo la kafukufuku wochokera ku Lundbeck ndi mabungwe a UK funding (NIHR, MRC, Wellcome Trust).
Olembawo akunena kuti palibe mikangano ina ya chidwi pa ntchitoyi.
Pomaliza,�Ngakhale kafukufuku wochuluka wapeza mazana a biomarkers za kupsinjika maganizo, si ambiri omwe adatsimikiza gawo lawo pa matenda ovutika maganizo kapena momwe chidziwitso cha biologic chingagwiritsiridwe ntchito kupititsa patsogolo matenda, chithandizo ndi matenda. Komabe, nkhani yomwe ili pamwambayi ikuwunikiranso zolemba zomwe zilipo za biomarkers zomwe zimakhudzidwa panthawi zina ndikufanizira zomwe zapezedwa ndi za kupsinjika maganizo. Kuphatikiza apo, zatsopano zomwe zapezeka pa biomarkers za kukhumudwa zingathandize kuzindikira kukhumudwa kuti athe kutsatira chithandizo chabwino. Zambiri zomwe zatchulidwa kuchokera ku National Center for Biotechnology Information (NCBI).�Zomwe tikudziwa zimangokhudza chiropractic komanso kuvulala kwa msana ndi mikhalidwe. Kuti mukambirane nkhaniyi, chonde muzimasuka kufunsa Dr. Jimenez kapena mutitumizireni pa�915-850-0900 .
Wosankhidwa ndi Dr. Alex Jimenez
Mitu Yowonjezera: Ululu Wobwerera
Ululu wammbuyo ndi chimodzi mwa zifukwa zofala kwambiri za olumala ndi masiku osowa kuntchito padziko lonse lapansi. Kunena zoona, kupweteka kwa msana kwanenedwa kuti ndi chifukwa chachiwiri chofala kwambiri choyendera ofesi ya dokotala, choposa kokha ndi matenda apamwamba opuma. Pafupifupi 80 peresenti ya anthu adzakhala ndi mtundu wina wa ululu wammbuyo kamodzi pa moyo wawo wonse. Msana ndi dongosolo lovuta lopangidwa ndi mafupa, mafupa, mitsempha ndi minofu, pakati pa ziwalo zina zofewa. Chifukwa cha izi, kuvulala ndi / kapena zovuta, monga herniated discs, pamapeto pake zimatha kuyambitsa zizindikiro za ululu wammbuyo. Kuvulala kwamasewera kapena ngozi zapamsewu nthawi zambiri zimakhala zomwe zimayambitsa kupweteka kwa msana, komabe, nthawi zina kuyenda kosavuta kumakhala ndi zotsatira zowawa. Mwamwayi, njira zina zochiritsira, monga chisamaliro cha chiropractic, zingathandize kuchepetsa ululu wammbuyo pogwiritsa ntchito kusintha kwa msana ndi kusintha kwamanja, potsirizira pake kumathandiza kuchepetsa ululu.
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nyamakazi ululu ndi chinthu chovuta kwambiri chomwe chimaphatikizapo kukonzanso kwa neurophysiological pamagulu onse a njira yowawa. Njira zochiritsira zomwe zilipo kuti muchepetse ululu m'malo olumikizirana mafupa ndizochepa, ndipo odwala nyamakazi ambiri amangopereka chithandizo chochepetsera ululu ndi chithandizo chamakono. Kumvetsetsa bwino njira za mitsempha zomwe zimayambitsa kupweteka kwa minofu ndi kuzindikira zolinga zatsopano zidzathandiza kupanga mankhwala ochiritsira amtsogolo. Nkhaniyi ikuwunikanso kafukufuku wina waposachedwa pazifukwa zomwe zimapangitsa kuti pakhale kupweteka kwapakati komanso kukhudza madera monga cannabinoids, proteinase-activated receptors, sodium channels, cytokines, and transient receptor njira. Malingaliro omwe akubwera akuti osteoarthritis akhoza kukhala ndi gawo la neuropathic amakambidwanso.
Introduction
Bungwe la zaumoyo padziko lonse lapansi likuwona kuti matenda a musculoskeletal ndi omwe amachititsa olumala kwambiri masiku ano, zomwe zimakhudza munthu mmodzi mwa atatu akuluakulu [1]. Chodetsa nkhaŵa kwambiri n’chakuti kuchuluka kwa matendaŵa kukuchulukirachulukira pamene kudziwa kwathu zifukwa zake n’kwachikalekale.
Chithunzi 1 Chithunzi chosonyeza zina mwazolinga zomwe zimadziwika kuti zimachepetsa ululu wamagulu. Neuromodulators akhoza kumasulidwa kuchokera ku mitsempha ya mitsempha komanso maselo a mast ndi macrophages kuti asinthe afferent mechanosensitivity. Endovanilloids, asidi, ndi kutentha koyipa kumatha kuyambitsa njira zolandilira zomwe zitha kukhala zamtundu wa vanilloid 1 (TRPV1) zomwe zimatsogolera kutulutsa kwa algogenic substance P (SP), yomwe pambuyo pake imamanga ku neurokinin-1 (NK1) receptors. Mapuloteni amatha kung'amba ndi kulimbikitsa zolandilira ma protease-activated (PARs). Pakadali pano, PAR2ndi PAR4awonetsedwa kuti amathandizira olowa nawo limodzi. Endocannabinoid anandamide (AE) imapangidwa pofunidwa ndikupangidwa kuchokera ku N-arachidonoyl phosphatidylethanolamine (NAPE) pansi pa enzymatic action of phospholipases. Gawo la AE kenako limamangiriza ku cannabinoid-1 (CB1) zolandilira zomwe zimatsogolera ku neuronal deensitization. AE yopanda malire imatengedwa mwachangu ndi anandamide membrane transporter (AMT) isanaphwanyidwe ndi fatty acid amide hydrolase (FAAH) kukhala ethanolamine (Et) ndi arachidonic acid (AA). The cytokines tumor necrosis factor-?(TNF-?), interleukin-6 (IL-6) ndi interleukin1-beta (IL-1?) Ikhoza kumangirira ku zolandilira zawo kuti apititse patsogolo kufala kwa ululu. Pomaliza, ma tetrodotoxin (TTX)-resistant sodium channels (Nav1.8) amakhudzidwa ndi neuronal sensitization.
Odwala amafuna awo Ululu wopweteka kutha; komabe, ma analgesics omwe amaperekedwa pakali pano sagwira ntchito ndipo amatsagana ndi zovuta zambiri zosafunika. Momwemonso, mamiliyoni a anthu padziko lonse lapansi akuvutika ndi zofooketsa za ululu wamagulu, zomwe palibe chithandizo chokwanira [2].
Mitundu yopitilira 100 ya nyamakazi imakhala ndi osteoarthritis (OA) yomwe ndiyofala kwambiri. OA ndi matenda olowa m'malo olumikizana pang'onopang'ono omwe amayambitsa kupweteka kosalekeza komanso kutayika kwa ntchito. Nthawi zambiri, OA ndikulephera kwa mgwirizanowo kukonza zowonongeka bwino poyankha mphamvu zochulukirapo zomwe zimayikidwapo. Zomwe zamoyo ndi zamaganizo zomwe zimakhala ndi ululu wa OA sizimamveka bwino, ngakhale kufufuza kosalekeza kumavumbula zovuta za zizindikiro za matenda [2]. Thandizo lamakono, monga mankhwala osagwiritsa ntchito steroidal anti-inflammatory (NSAIDs), amapereka mpumulo wa zizindikiro, kuchepetsa ululu kwa nthawi yochepa, koma samachepetsa ululu pa nthawi yonse ya moyo wa wodwalayo. Komanso, mlingo waukulu wa NSAIDs sungakhoze kutengedwa mobwerezabwereza kwa zaka zambiri, chifukwa izi zingayambitse kuopsa kwa aimpso ndi kutuluka kwa m'mimba.
Mwachizoloŵezi, kafukufuku wa nyamakazi wayang'ana kwambiri pa articular cartilage monga chandamale choyambirira cha mankhwala ochiritsira a OA mankhwala osintha matenda. Cholinga cha chondrogenic ichi chawonetsa kuwala kwatsopano pazinthu zovuta za biochemical ndi biomechanical zomwe zimakhudza khalidwe la chondrocyte m'magulu odwala. Komabe, popeza cartilage ya articular ndi ya aneural ndi avascular, minofu iyi sichingakhale gwero la ululu wa OA. Izi, kuphatikizapo zomwe zapeza kuti palibe mgwirizano pakati pa kuwonongeka kwa cartilage ndi ululu kwa odwala OA [3,4] kapena zitsanzo za preclinical za OA [5], zachititsa kuti pakhale kusintha kwa kupanga mankhwala kuti athe kuchepetsa ululu. . Nkhaniyi iwonanso zomwe zapezedwa posachedwa mu kafukufuku wa ululu wophatikizana ndikuwunikira zina mwazolinga zomwe zikubwera zomwe zingakhale zam'tsogolo za kasamalidwe ka ululu wa nyamakazi (mwachidule mu Fig. 1)
Makina a Cytokines
Zochita za ma cytokines osiyanasiyana mu maphunziro a neurophysiology ophatikizana zawonekera kwambiri posachedwa. Interleukin-6 (IL-6), mwachitsanzo, ndi cytokine yomwe nthawi zambiri imamangiriza ku IL-6 receptor (IL-6R). IL-6 imathanso kuwonetsa pomanga ndi IL-6R (SIL-6R) yosungunuka kuti ipange zovuta za IL-6 / sIL-6R. IL-6 / sIL-6R zovuta zotsatizanazi zimamangiriza ku transmembrane glycoprotein subunit 130 (gp130), motero amalola IL-6 kuwonetsa m'maselo omwe samawonetsa IL-6R [25,26]. IL-6 ndi SIL-6R ndizofunikira kwambiri pakutupa kwachilengedwe komanso nyamakazi, popeza kuwongolera zonse kwapezeka mu seramu ya odwala a RA ndi synovial fluid. [27,29, 6] Posachedwapa, Vazquez et al.observed kuti kugwirizanitsa IL-6 / sIL-30R mu mawondo a makoswe kumayambitsa ululu wotupa, monga momwe zasonyezedwera ndi kuwonjezeka kwa kuyankhidwa kwa mitsempha ya msana wa dorsal horn neurons ku kukondoweza kwa bondo ndi mbali zina. wa m'mbuyo [6]. Kuthamanga kwa mitsempha ya msana kunawonekeranso pamene IL-6 / sIL-130R inagwiritsidwa ntchito kumaloko kumtunda wa msana. Kugwiritsa ntchito msana kwa soluble gp6 (komwe kungapangitse ma IL-6/sIL-6R, potero kuchepetsa trans-signaling) kuletsa IL-6/sIL-130R-induced central sensitization. Komabe, kugwiritsa ntchito kwambiri sungunuka gpXNUMX kokha sikunachepetse mayankho a neuronal ku kutupa komwe kunakhazikitsidwa kale.
Njira za transient receptor potential (TRP) ndizosasankha njira zolumikizirana zomwe zimakhala ngati zophatikizira njira zosiyanasiyana zakuthupi ndi zapathophysiological. Kuphatikiza pa thermosensation, chemosensation, ndi mechanosensation, njira za TRP zimakhudzidwa ndi kusintha kwa ululu ndi kutupa. Mwachitsanzo, njira za ion za TRP vanilloid-1 (TRPV1) zasonyezedwa kuti zikuthandizira kupweteka kwapakhosi monga kutentha kwa hyperalgesia sikunatuluke mu TRPV1 mbewa za monoarthritic [31]. Mofananamo, TRP ankyrin-1 (TRPA1) njira za ion zimakhudzidwa ndi arthritic mechano hypersensitivity monga kutsekeka kwa receptor ndi otsutsa omwe amalepheretsa kupweteka kwa mawotchi mu Freunds adjuvant adjuvant model inflammation [32,33]. Umboni wina wosonyeza kuti TRPV1 ikhoza kukhudzidwa ndi ululu wa OA umachokera ku maphunziro omwe neuronal TRPV1 mawu amakwezedwa mu sodium monoiodoacetate model of OA [34]. Kuphatikiza apo, kasamalidwe kachitidwe ka TRPV1 antagonist A-889425 adachepetsa zomwe zidachitika komanso zodziwikiratu zamitundu yosiyanasiyana ya msana komanso ma neuron enieni amtundu wa monoiodoacetate [35]. Deta iyi imasonyeza kuti endovanilloids ikhoza kuphatikizidwa muzochitika zapakati zolimbikitsana ndi ululu wa OA.
Pakali pano amadziwika kuti ali ndi ma polymorphisms anayi mu jini yomwe imayika TRPV1, zomwe zimatsogolera ku kusintha kwa kamangidwe ka njira ya ion ndi kuwonongeka kwa ntchito. Polymorphism imodzi (rs8065080) imasintha kukhudzika kwa TRPV1 ku capsaicin, ndipo anthu omwe ali ndi polymorphism iyi sakhudzidwa kwambiri ndi kutentha kwa hyperalgesia [36]. Kafukufuku waposachedwa adawona ngati odwala OA omwe ali ndi rs8065080 polymorphism adakumana ndi zowawa zosinthika motengera chibadwa chamtunduwu. Gulu lofufuza lidapeza kuti odwala omwe ali ndi ma asymptomatic bondo OA amatha kunyamula jini ya rs8065080 kuposa odwala omwe ali ndi mafupa opweteka. [37]. Izi zikusonyeza kuti OA odwala ndi ntchito bwinobwino; Njira za TRPV1 zimakhala ndi chiopsezo chowonjezereka cha ululu wamagulu ndipo zimatsimikiziranso kuti TRPV1 ikhoza kutengapo mbali mukumva kupweteka kwa OA.
Kutsiliza
Ngakhale cholepheretsa kuchiza ululu wa nyamakazi chidakalipo, kudumphadumpha kwakukulu kukuchitika pakumvetsetsa kwathu njira za neurophysiological zomwe zimayambitsa kupweteka kwa mafupa. Zolinga zatsopano zikuzindikiridwa mosalekeza, pomwe njira zoyendetsera njira zodziwika zikufotokozedwa ndikukonzedwanso. Kutsata cholandirira chimodzi kapena njira ya ion sikutheka kukhala njira yothetsera ululu wamagulu, koma m'malo mwake njira ya polypharmacy imasonyezedwa momwe oyimira pakati osiyanasiyana amagwiritsidwa ntchito limodzi panthawi inayake ya matendawa. Kutsegula mayendedwe ogwira ntchito pamlingo uliwonse wa njira yowawa kumathandizanso kudziwa kwathu momwe ululu wamagulu umapangidwira. Mwachitsanzo, kuzindikira oyimira pakati pa ululu wamagulu kumatithandiza kuti tizitha kulamulira nociception mkati mwa mgwirizanowu ndipo mwina tipewe zotsatira zapakati za pharmacotherapeutics zomwe zimayendetsedwa mwadongosolo.
FACETOGENIC PAIN
FACET SYNDROME & FACETOGENIC PAIN
Facet syndrome ndi matenda a articular okhudzana ndi ziwalo za m'chiuno ndi momwe zimakhalira ndipo zimabweretsa ululu wamtundu uliwonse komanso wonyezimira.
Kuzungulira mopitirira muyeso, kutambasula, kapena kupindika kwa msana (kugwiritsiridwa ntchito mobwerezabwereza) kungayambitse kusintha kosasinthika kwa cartilage ya olowa. Kuonjezera apo, zikhoza kuphatikizira kusintha kosasinthika kuzinthu zina, kuphatikizapo intervertebral disc.
Kupweteka ndi / kapena kuchepetsa kufalikira ndi kuzungulira
Kukoma mtima pa palpation
Kupweteka kwa facetogenic komweko kapena m'mapewa kapena kumtunda kumbuyo, ndipo sikumawonekera kutsogolo kapena pansi pa mkono kapena zala monga herniated disc ingathere.
LUMBAR FACET SYNDROME & FACETOGENIC PAIN
Kupweteka kapena kupweteka m'munsi kumbuyo.
Kukoma mtima / kuuma kwa m'deralo pambali pa msana kumunsi kumbuyo.
Ululu, kuuma, kapena kuvutika ndi mayendedwe ena (monga kuyimirira mowongoka kapena kudzuka pampando.
Ululu pa hyperextension
Ululu wodziwika kuchokera kumtunda wa m'chiuno ukhoza kupitirira mu ntchafu, m'chiuno, ndi kumtunda.
Kupweteka kochokera m'munsi mwa ntchafu kumatha kulowa mkati mwa ntchafu, kutsogolo ndi / kapena kumbuyo.
L4-L5 ndi L5-S1 mbali zolumikizira zimatha kutanthauza kupweteka komwe kumapitilira mwendo wakumbuyo, ndipo nthawi zina, mpaka kumapazi.
MANKHWALA OCHOKERA UMBONI
Umboni Wochokera ku Umboni Wothandizira Ululu wa Mankhwala malinga ndi Clinical Diagnoses
12. Ululu Wochokera ku Lumbar Facet Joints
Kudalirika
Ngakhale kuti kukhalapo kwa facet syndrome kunali kokayikiridwa kwa nthawi yayitali, tsopano kumavomerezedwa ngati gulu lachipatala. Malingana ndi njira zodziwira matenda, ziwalo za zygapophysial zimayambira pakati pa 5% ndi 15% ya milandu yaukali, axial low back back. Nthawi zambiri, ululu wa facetogenic umabwera chifukwa cha kupsinjika mobwerezabwereza komanso / kapena kupwetekedwa mtima pang'ono, komwe kumayambitsa kutupa ndi kutambasuka kwa kapisozi olowa. Madandaulo omwe amapezeka pafupipafupi ndi axial low back ululu ndi kuwawa komwe kumawoneka m'mbali, m'chiuno, ndi ntchafu. Palibe zizindikiro zapathognomonic zodziwikiratu. Chizindikiro champhamvu kwambiri cha ululu wa lumbar facetogenic ndikuchepetsa ululu pambuyo pa mankhwala oletsa ululu a rami mediales (nthambi zapakati) za rami dorsales zomwe sizimakhudza mbali zonse. Chifukwa chabodza komanso, mwina, zotsatira zabodza zitha kuchitika, zotsatira zake ziyenera kutanthauziridwa mosamala. Odwala omwe ali ndi jekeseni-otsimikiziridwa ndi ululu wa zygapophysial, njira zothandizira zikhoza kuchitidwa potsata ndondomeko ya mankhwala osiyanasiyana, kuphatikizapo mankhwala, mankhwala ochiritsira, ndi kuchita masewera olimbitsa thupi nthawi zonse, ndipo, ngati asonyezedwa, psychotherapy. Pakadali pano, muyezo wagolide wochizira ululu wa facetogenic ndi chithandizo cha radiofrequency (1 B+). Umboni wothandizira intra-articular corticosteroids ndi wochepa; chifukwa chake, izi ziyenera kusungidwa kwa iwo omwe samayankha chithandizo cha radiofrequency (2 B1).
Ululu wa Facetogenic wochokera m'magulu amtundu wa lumbar ndizomwe zimayambitsa kupweteka kwa msana mwa anthu akuluakulu. Goldthwaite ndiye anali woyamba kufotokoza za matendawa mu 1911, ndipo Ghormley amadziwika kuti ndi amene anayambitsa mawu akuti �facet syndrome mu 1933. , synovial membrane, hyaline cartilage, ndi fupa.35
Nthawi zambiri, zimakhala chifukwa cha kupsinjika mobwerezabwereza komanso/kapena kupwetekedwa mtima kocheperako. Izi zimabweretsa kutupa, zomwe zingapangitse kuti mbaliyi ikhale yodzaza ndi madzi ndi kutupa, zomwe zimapangitsa kutambasula kwa capsule yolumikizana ndi ululu wotsatira.[27] Kusintha kotupa kozungulira gawo limodzi kumatha kukwiyitsanso mitsempha ya msana kudzera pa foraminal narrowing, zomwe zimapangitsa sciatica. Kuphatikiza apo, Igarashi et al.28 adapeza kuti ma cytokines otupa omwe amatulutsidwa kudzera mu kapsule yolumikizana ndi ventral kwa odwala omwe ali ndi vuto la zygapophysial olowa nawo amatha kukhala ndi gawo lazizindikiro za neuropathic mwa anthu omwe ali ndi spinal stenosis. Zomwe zimayambitsa kupweteka kwa zygapophysial zimaphatikizapo spondylolisthesis / lysis, degenerative disc matenda, ndi ukalamba.5
IC ZOWONJEZERA ZOYESA
Kuchuluka kwa kusintha kwa ma pathological m'malo olumikizirana nawo pamawunikidwe a radiology kumatengera zaka zomwe anthu omwe akuphunzirawo, njira yaukadaulo yomwe imagwiritsidwa ntchito, komanso tanthauzo la zolakwika. Magawo osokonekera amatha kuwonedwa bwino pogwiritsa ntchito mayeso a computed tomography (CT)..49
NEUROPATHIC PAIN
Ululu unayambika kapena woyambitsidwa ndi chotupa chachikulu kapena kusagwira bwino ntchito mu dongosolo lamanjenje la somatosensory.
Kupweteka kwa mtima nthawi zambiri imakhala yosatha, yovuta kuchiza, ndipo nthawi zambiri imalimbana ndi kasamalidwe koyenera ka analgesic.
Kudalirika
Ululu wa neuropathic umayamba chifukwa cha zilonda kapena matenda a somatosensory system, kuphatikizapo zotumphukira zotumphukira (A?, A? ndi C fibers) ndi ma neurons apakati, ndipo zimakhudza 7-10% ya anthu ambiri. Zambiri zomwe zimayambitsa kupweteka kwa neuropathic zafotokozedwa. Chiwopsezo chake chikuyembekezeka kukwera chifukwa cha ukalamba padziko lonse lapansi, kuchuluka kwa shuga mellitus, komanso kupulumuka bwino ku khansa pambuyo pa chemotherapy. Zoonadi, kusagwirizana pakati pa zizindikiro zokondweretsa ndi zolepheretsa somatosensory, kusintha kwa njira za ion, ndi kusinthasintha kwa mauthenga opweteka m'kati mwa dongosolo la mitsempha zonse zakhala zikukhudzidwa ndi ululu wa neuropathic. Komanso, kulemedwa kwa ululu wopweteka waumphawi kumawoneka wokhudzana ndi zovuta za zizindikiro za neuropathic, zotsatira zosauka, ndi zosankha zovuta za chithandizo. Chofunika kwambiri, ubwino wa moyo umasokonekera kwa odwala omwe ali ndi ululu wa neuropathic chifukwa cha kuchuluka kwa mankhwala osokoneza bongo komanso kuyendera kwa opereka chithandizo chamankhwala komanso kudwala kwa ululu wokha komanso matenda oyambitsa matenda. Ngakhale kuti pali zovuta, kupita patsogolo pakumvetsetsa kwa matenda a ululu wa neuropathic kumapangitsa kuti pakhale njira zatsopano zodziwira matenda ndi njira zothandizira anthu payekha, zomwe zimatsindika kufunikira kokhala ndi njira zambiri zoyendetsera ululu wa neuropathic.
PATHOGENESIS YA NEUROPATHIC PAIN
ZINTHU ZONSE
Pambuyo pa zotumphukira mitsempha chotupa, ma neuron amakhala tcheru kwambiri ndi kukhala ndi chisangalalo chachilendo komanso kukhudzika kokwezeka kwa kukondoweza.
Kupweteka kwapakhosi kwaumphawi kumachitika kawirikawiri kwa amayi (8% motsutsana ndi 5.7% mwa amuna) ndi odwala> zaka 50 (8.9% motsutsana ndi 5.6% mwa omwe ali ndi zaka <49 zaka), ndipo nthawi zambiri amakhudza msana ndi miyendo yapansi. , khosi ndi miyendo yakumtunda24. Lumbar ndi khomo lachiberekero radiculopathies zowawa mwina ndizomwe zimayambitsa kupweteka kwambiri kwa neuropathic. Mogwirizana ndi detayi, kafukufuku wa > Odwala a 12,000 omwe ali ndi ululu wosatha ndi mitundu yonse ya ululu wa nociceptive ndi neuropathic, omwe amatchulidwa kwa akatswiri a ululu ku Germany, adawonetsa kuti 40% ya odwala onse adakumana ndi zizindikiro zina za ululu wa ubongo (monga kutentha kutentha, mwachitsanzo, 25% ya odwala onse omwe ali ndi vuto la kupweteka kwa msana, monga kupweteka kwa m'mimba, mwachitsanzo, kuvulala kwa ubongo). kutopa, ndi kufooka); odwala omwe ali ndi ululu wopweteka kwambiri komanso radiculopathy anakhudzidwa makamakaXNUMX.
Kuthandizira kwachipatala cha neurophysiology pakumvetsetsa kwa njira zamutu wazovuta.
Kudalirika
Pakalipano, maphunziro a zachipatala a neurophysiological pamutu wamtundu wa tension-type (TTH) achitidwa ndi zolinga zazikulu ziwiri: (1) kuti adziwe ngati zizindikiro zina za neurophysiological zingakhale ngati zizindikiro za TTH, ndi (2) kufufuza za physiopathology ya TTH. Ponena za mfundo yoyamba, zotsatira zomwe zilipo panopa ndi zokhumudwitsa chifukwa zolakwika zina zomwe zimapezeka mwa odwala TTH zikhoza kuwonetsedwanso kawirikawiri kwa odwala migraine. Kumbali inayi, neurophysiology yachipatala yatenga gawo lofunikira pakukangana kwapathogenesis ya TTH. Kafukufuku wokhudzana ndi kuponderezedwa kwapang'onopang'ono kwa minyewa ya temporalis apeza kukanika kwa kusangalatsa kwaubongo komanso kuwongolera kwapamwamba. Mfundo yofananayi yafikiridwa pogwiritsa ntchito ma trigeminocervical reflexes, omwe zolakwika zawo mu TTH zasonyeza kuti ntchito yochepetsera yolepheretsa ubongo wa interneurons, kusonyeza njira zochepetsera kupweteka kwamkati. Chochititsa chidwi n'chakuti, kusokonezeka kwa neural excitability mu TTH kumawoneka ngati chodabwitsa, osati kumadera a cranial. Njira zosalongosoka za DNIC zawonetsedwanso m'maboma a somatic ndi maphunziro a nociceptive flexion reflex. Tsoka ilo, maphunziro ambiri a neurophysiological pa TTH amasokonezedwa ndi zolakwika zazikulu zamakina, zomwe ziyenera kupewedwa mu kafukufuku wamtsogolo kuti afotokoze bwino njira za TTH.
Zothandizira:
Neurophysiology ya ululu wa nyamakazi. McDougall JJ1 Linton P.
Kupweteka kochokera ku lumbar facet. van Kleef M1,Vanelderen P,Cohen SP,Lataster A,Van Zundert J,Mekhail N.
Kupweteka kwa mtimaLuana Colloca,1Taylor Ludman,1Didier Bouhassira,2Ralf Baron,3Anthony H. Dickenson,4David Yarnitsky,5Roy Freeman,6Andrea Truini,7Nadine Attal, Nanna B. Finnerup,9Christopher Eccleston,10,11Eija Kalso,12David L. Bennett,13Robert H. Dworkin,14ndi Srinivasa N. Raja15
Kuthandizira kwachipatala cha neurophysiology pakumvetsetsa kwa njira zamutu wazovuta. Rossi P1, Vollono C, Valeriani M, Sandrini G.
Kupweteka kosatha ndi vuto laumoyo wa anthu lomwe likukhudza 20�30% ya anthu akumayiko akumadzulo. Ngakhale kuti pakhala pali chitukuko chochuluka cha sayansi pakumvetsetsa kwa neurophysiology ya ululu, kuwunika bwino ndi kuzindikira vuto la kupweteka kwapang'onopang'ono kwa wodwala silolunjika kapena lodziwika bwino. Momwe kupweteka kosalekeza kumaganiziridwa kumakhudza momwe ululu umayesedwa komanso zinthu zomwe zimaganiziridwa popanga matenda opweteka kwambiri. Palibe ubale pakati pa kuchuluka kapena mtundu wa organic pathology ndi kupweteka kwambiri, koma m'malo mwake, kupweteka kosalekeza kumapangidwa ndi miyandamiyanda ya biomedical, psychosocial (monga zikhulupiriro za odwala, ziyembekezo, ndi maganizo), ndi makhalidwe (monga nkhani, mayankho a ena ofunika). Kuwunika madera atatuwa kudzera mukuwunika mozama kwa munthu yemwe ali ndi ululu wosaneneka ndikofunikira pazisankho zamankhwala komanso kuti pakhale zotsatira zabwino. Kuwunikaku kuyenera kukhala ndi mbiri ya wodwala komanso kuwunika kwachipatala komanso kuyankhulana kwakanthawi kochepa komwe wodwalayo angawonedwe. Kuwunika kwinanso kuti athe kuthana ndi mafunso omwe adadziwika pakuwunika koyambirira kudzawongolera zisankho za mayeso owonjezera, ngati alipo, omwe angakhale oyenera. Zida zodziwonetsera zokhazokha kuti ziwone kukula kwa ululu wa wodwalayo, mphamvu zogwirira ntchito, zikhulupiriro ndi ziyembekezo, ndi kupsinjika maganizo zilipo, ndipo zikhoza kuperekedwa ndi dokotala, kapena kutumizidwa kuti afufuze mozama angapangidwe kuti athandizidwe pokonzekera chithandizo.
Ululu ndi chizindikiro chofala kwambiri. Kupweteka kosalekeza kokha kumaganiziridwa kuti kumakhudza 30% ya anthu akuluakulu a ku USA, oposa 100 miliyoni akuluakulu.1
Ngakhale kuti kukwera mtengo kwa chithandizo cha anthu omwe ali ndi ululu wosatha, mpumulo wa ambiri umakhalabe wovuta ndipo kuthetsa ululu konseko ndikosowa. Ngakhale kuti pakhala pali kupita patsogolo kwakukulu mu chidziwitso cha neurophysiology ya ululu, pamodzi ndi chitukuko cha mankhwala amphamvu a analgesic ndi njira zina zatsopano zachipatala ndi opaleshoni, pafupifupi kuchuluka kwa kuchepetsa ululu ndi njira zomwe zilipo ndi 30�40% ndipo izi zimachitika ochepera theka la odwala omwe amathandizidwa.
Momwe timaganizira za ululu zimakhudza momwe timayendera momwe timayendera zowawa. Kuwunika kumayamba ndi mbiri yakale komanso kuyezetsa thupi, kutsatiridwa, ndikuyesa ma labotale ndi njira zowunikira poyesa kuzindikira ndi / kapena kutsimikizira kupezeka kwa matenda aliwonse omwe amayambitsa zizindikiro kapena jenereta ululu.
Ngati palibe chidziwitso chodziwika bwino cha organic pathology, wothandizira zaumoyo angaganize kuti lipoti lazizindikiro limachokera kumalingaliro amalingaliro ndipo atha kupempha kuunika kwamalingaliro kuti azindikire zomwe zimayambitsa lipoti la wodwalayo. Pali zapawiri pomwe lipoti lazizindikiro limanenedwa ndi mwina somatic or njira za psychogenic.
Mwachitsanzo, maziko a organic omwe amapezeka kwambiri komanso obwera mobwerezabwereza (monga mutu wa mutu)3 ndi osachiritsika [mwachitsanzo. ululu wammbuyo, fibromyalgia (FM)] mavuto opweteka kwambiri sakudziwika, 4,5 pamene kumbali ina, anthu opanda zizindikiro angakhale ndi zolakwika zapangidwe monga ma discs a herniated omwe angafotokoze ululu ngati alipo.6,7�Palibe kufotokoza kokwanira kwa odwala omwe sanadziwike kuti ali ndi vuto la organic omwe amafotokoza zowawa kwambiri komanso anthu opanda ululu omwe ali ndi vuto lalikulu, lofuna kuchita bwino.
Kupweteka kosatha kumakhudza zambiri osati wodwala payekha, komanso ena ake ofunika (abwenzi, achibale, olemba ntchito ndi ogwira nawo ntchito ndi mabwenzi).), kupanga chithandizo choyenera kukhala chofunikira. Chithandizo chokhutiritsa chimangobwera kuchokera pakuwunika mozama za momwe biological etiology ya ululuyo imayendera limodzi ndi momwe wodwalayo amafotokozera m'maganizo ndi m'makhalidwe, kuphatikiza momwe amamvera (monga nkhawa, kukhumudwa, kukwiya), kuzindikira komanso kumvetsetsa kwazizindikiro, komanso momwe amamvera. zizindikiro ndi ena ofunika kwambiri.8,9 Mfundo yofunika kwambiri ndi yakuti zinthu zambiri zimakhudza zizindikiro ndi zofooka za anthu omwe ali ndi ululu wosatha. Choncho, kufufuza kwakukulu kumafunika komwe kumakhudza madera a biomedical, psychosocial, ndi makhalidwe, chifukwa aliyense amathandizira kupweteka kosalekeza ndi kulemala kofanana.10,11
Kuwunika Kwathunthu Kwa Munthu Amene Ali ndi Ululu Wosatha
Turk ndi Meichenbaum12 adanena kuti mafunso atatu apakati ayenera kutsogolera kuwunika kwa anthu omwe amafotokoza ululu:
Kodi matenda kapena kuvulala kwa wodwalayo (kuwonongeka kwa thupi) ndi kotani?
Kodi kukula kwa matendawa ndi kotani? Ndiko kuti, kodi wodwala akuvutika, wolumala, ndi kulephera kusangalala ndi zochita za masiku onse mpaka pati?
Kodi khalidwe la munthuyo likuwoneka loyenera ku matenda kapena kuvulala, kapena pali umboni uliwonse wa kukulitsa zizindikiro pa zifukwa zosiyanasiyana za maganizo kapena chikhalidwe (monga ubwino monga chisamaliro chabwino, mankhwala osintha maganizo, malipiro a ndalama)?
Kuti tiyankhe mafunsowa, chidziwitso chiyenera kusonkhanitsidwa kuchokera kwa wodwalayo ndi mbiri yakale ndi kuunika kwa thupi, kuphatikizapo kuyankhulana kwachipatala, komanso kupyolera mu zida zowunikira zovomerezeka. Othandizira azaumoyo amayenera kufunafuna chifukwa chilichonse cha ululu kudzera mu kuyezetsa thupi ndi kuyezetsa matenda pomwe akuwunika momwe wodwalayo alili, mantha, ziyembekezo zake, zoyeserera, zothandizira, mayankho a ena ofunikira, komanso momwe ululu umakhudzira odwala. moyo.11 Mwachidule, wothandizira zaumoyo ayenera kuwunika "munthu yense" osati kupweteka kokha.
Zolinga zonse za mbiriyakale ndi kuwunika kwachipatala ndi:
(i) kudziwa kufunikira kwa kuyezetsa kowonjezera kwa matenda
(ii) kudziwa ngati deta yachipatala ikhoza kufotokozera zizindikiro za wodwalayo, kuopsa kwa zizindikiro, ndi zofooka zake
Odwala ambiri omwe amamva kupweteka kosalekeza samasonyeza kuti alibe matenda pogwiritsa ntchito ma radiographs, computed axial tomography scans, kapena electromyography. (mabuku ochulukirapo amapezeka pakuwunika kwakuthupi, njira zowunikira ma radiographic ndi ma laboratory kuti adziwe maziko akuthupi a ululu), 17 kupangitsa kuti kuzindikirika kwa matenda kukhale kovuta kapena kosatheka.
Ngakhale kuti pali zolephera izi, mbiri ya wodwalayo ndi kuunika kwa thupi kumakhalabe maziko a chithandizo chamankhwala, kungapereke chitetezo chopanda kutanthauzira mopitirira muyeso kuchokera ku zojambula zowonongeka zomwe makamaka zimatsimikizira, ndipo zingagwiritsidwe ntchito kutsogolera chitsogozo cha zoyesayesa zowonjezereka.
Kuonjezera apo, odwala omwe ali ndi vuto lopweteka kwambiri nthawi zambiri amamwa mankhwala osiyanasiyana.18 Ndikofunika kukambirana za mankhwala amakono a wodwala panthawi yofunsa mafunso, monga mankhwala opweteka ambiri amagwirizanitsidwa ndi zotsatira zomwe zingayambitse kapena kutsanzira kupsinjika maganizo.19 Othandizira zaumoyo sayenera kudziŵa bwino mankhwala omwe amagwiritsidwa ntchito pa ululu wosatha, komanso ndi zotsatira za mankhwalawa zomwe zimabweretsa kutopa, kugona, ndi kusintha kwa maganizo kuti asamadziwe bwino za kuvutika maganizo.
Kugwiritsiridwa ntchito kwa ma diaries a tsiku ndi tsiku kumakhulupirira kuti ndikolondola kwambiri chifukwa kumachokera pa nthawi yeniyeni osati kukumbukira. Odwala atha kufunsidwa kuti azisunga zolemba zanthawi zonse zowawa zomwe zimalembedwa kangapo tsiku lililonse (mwachitsanzo, chakudya ndi nthawi yogona) kwa masiku angapo kapena milungu ingapo komanso kuchuluka kwa zowawa kumatha kuwerengedwa nthawi yonseyi.
Vuto limodzi lodziwika ndi kugwiritsa ntchito mapepala a mapepala ndi pensulo ndiloti odwala sangatsatire malangizo oti apereke mavoti pakapita nthawi. M'malo mwake, odwala amatha kulemba zolemba zawo pasadakhale (�kudzaza mtsogolo) kapena asanapite kukaonana ndi dokotala (�kubwerera chammbuyo), 24 kulepheretsa kutsimikizika kwa zolembazo. Zolemba pakompyuta zalandira kuvomerezedwa mu maphunziro ena ofufuza kuti apewe mavutowa.
Kafukufuku wasonyeza kufunika kowunika moyo wonse wokhudzana ndi thanzi labwino (HRQOL) kwa odwala opweteka kwambiri kuphatikizapo ntchito.31,32 Pali njira zingapo zokhazikitsidwa bwino, zothandizidwa ndi psychometrically HRQOL [Zotsatira Zachipatala Phunziro la Short-Form Health Survey. (SF-36)], 33 miyeso yambiri ya thupi [monga Pain Disability Index (PDI)], 34 ndi miyeso yeniyeni ya matenda [monga Western Ontario MacMaster Osteoarthritis Index (WOMAC); 35 Roland-Morris Back Pain Disability Questionnaire (RDQ) )]36 kuwunika ntchito ndi moyo wabwino.
Miyezo yokhudzana ndi matenda imapangidwa kuti iwunikire momwe vuto linalake limakhudzira (monga kupweteka ndi kuuma kwa anthu omwe ali ndi nyamakazi), pomwe njira zochizira zimatheketsa kuyerekeza momwe thupi limagwirira ntchito limodzi ndi vuto linalake komanso chithandizo chake ndi matenda ena osiyanasiyana. Zotsatira zenizeni za vuto sizingadziwike pogwiritsira ntchito muyeso wa generic; Choncho, njira zokhudzana ndi matenda zikhoza kuwonetsa kusintha kwakukulu kwachipatala kapena kuwonongeka kwa ntchito zinazake chifukwa cha chithandizo. Miyezo yodziwika bwino yogwirira ntchito ingakhale yothandiza poyerekeza odwala omwe ali ndi mitundu yosiyanasiyana ya zowawa. Kugwiritsiridwa ntchito kwa matenda okhudzana ndi matenda ndi ma generic kumathandizira kukwaniritsa zolinga zonse ziwiri.
Kukhalapo kwa kupsinjika maganizo kwa anthu omwe ali ndi ululu wosatha kumabweretsa vuto poyesa zizindikiro monga kutopa, kuchepa kwa ntchito, kuchepa kwa libido, kusintha kwa chilakolako, kusokonezeka kwa kugona, kulemera kapena kuchepa, komanso kukumbukira kukumbukira ndi kusokonezeka maganizo, chifukwa zizindikirozi zikhoza kukhala. zotsatira za ululu, kupsinjika maganizo, kapena mankhwala omwe amaperekedwa kuti athetse ululu.
Zida zapangidwa makamaka kwa odwala opweteka kuti awone kupsyinjika kwa maganizo, zotsatira za ululu pa miyoyo ya odwala � moyo, kudziletsa, makhalidwe olimbana nawo, ndi maganizo okhudza matenda, ululu, ndi opereka chithandizo chamankhwala.17
Mwachitsanzo, Beck Depression Inventory (BDI)39 ndi Profile of Mood States (POMS) 40 ndi zomveka bwino za psychometrically poyesa zizindikiro za kupsinjika maganizo, kupsinjika maganizo, ndi kusokonezeka maganizo, ndipo zakhala zikulimbikitsidwa kuti zigwiritsidwe ntchito m'mayesero onse achipatala. kupweteka kosalekeza;41 komabe, ziwerengerozo ziyenera kutanthauziridwa mosamala ndipo zofunikira za milingo ya kupsinjika maganizo zingafunikire kusinthidwa kuti zisawonongeke zolakwika.42
Lab Biomarkers Kwa Ululu
Ma biomarkers ndi mawonekedwe achilengedwe omwe angagwiritsidwe ntchito kuwonetsa thanzi kapena matenda. Pepalali likuwunikiranso maphunziro a biomarkers of low back pain (LBP) m'nkhani za anthu. LBP ndiyo yomwe imayambitsa kulemala, chifukwa cha matenda osiyanasiyana okhudzana ndi msana, kuphatikizapo intervertebral disc degeneration, disc herniation, spinal stenosis, ndi facet arthritis. Cholinga cha maphunzirowa ndi oyimira pakati otupa, chifukwa kutupa kumathandizira kuti pathogenesis ya disc degenesis ndi njira zowawa zogwirizana. Mochulukirachulukira, kafukufuku akuwonetsa kuti kukhalapo kwa oyimira pakati otupa kumatha kuyeza mwadongosolo m'magazi. Ma biomarkers awa amatha kukhala ngati zida zatsopano zowongolera chisamaliro cha odwala. Pakalipano, kuyankha kwa odwala kuchipatala sikudziwika ndi chiwerengero chachikulu cha kubwereza, ndipo, pamene chithandizo cha opaleshoni chingapereke kukonzanso kwa anatomical ndi kupweteka, zimakhala zovuta komanso zodula. Ndemangayi ikukhudza maphunziro omwe amachitidwa pa anthu omwe ali ndi matenda enieni komanso chiyambi chosadziwika cha LBP. Popeza mbiri ya chilengedwe ya LBP ikupita patsogolo, chikhalidwe cha kanthaŵi cha maphunziro chimagawidwa ndi nthawi ya zizindikiro / matenda. Maphunziro okhudzana ndi kusintha kwa ma biomarkers okhala ndi chithandizo amawunikidwanso. Pamapeto pake, zizindikiro za matenda a LBP ndi kuwonongeka kwa msana zimatha kudyetsa nthawi yamankhwala a msana payekha payekha payekha pochiza LBP.
Ma Biomarkers Pakupweteka Kwambiri kwa Neuropathic & Potential Application Mu Spinal Cord Stimulation
Ndemanga iyi inali yolunjika pakumvetsetsa zomwe zili mkati mwa thupi la munthu zimawonjezeka ndikuchepa ndikuwonjezeka kwa ululu wa neuropathic. Tidawunikanso maphunziro osiyanasiyana, ndikuwona kulumikizana pakati pa ululu wa neuropathic ndi zigawo za chitetezo chamthupi (dongosololi limateteza thupi ku matenda ndi matenda). Zomwe tapeza zidzakhala zothandiza makamaka pakumvetsetsa njira zochepetsera kapena kuthetsa kukhumudwa, kupweteka kwapang'onopang'ono kwa neuropathic kumabweretsa. Njira ya Spinal stimulation (SCS) ndi imodzi mwa njira zochepetsera bwino zochizira ululu. Kafukufuku wotsatira adzagwiritsa ntchito zomwe tapeza kuchokera ku ndemangayi kupita ku SCS, kuti timvetsetse momwe zimagwirira ntchito, ndikuwonjezeranso kuchita bwino.
Ma cytokines oyambitsa kutupa monga IL-1?, IL-6, IL-2, IL-33, CCL3, CXCL1, CCR5, ndi TNF-?, Apezeka kuti ali ndi udindo waukulu pakukulitsa mayiko opweteka kwambiri.
Titawunikanso maphunziro osiyanasiyana okhudzana ndi zolembera zowawa, tapeza kuti ma seramu a pro-inflammatory cytokines ndi chemokines, monga IL-1?, IL-6, IL-2, IL-33, CCL3, CXCL1, CCR5, ndi TNF. -?, anali olamulidwa kwambiri panthawi ya ululu wosatha. Kumbali ina, anti-inflammatory cytokines monga IL-10 ndi IL-4 anapezeka kuti akuwonetsa kutsika kwakukulu pa nthawi ya ululu wosatha.
Biomarkers for Depression
Kafukufuku wochuluka wakhudza mazana a ma biomarkers omwe amayambitsa kukhumudwa, koma sanafotokozere bwino za udindo wawo pa matenda ovutika maganizo kapena kutsimikizira zomwe zili zachilendo momwe odwala komanso momwe chidziwitso cha biologic chingagwiritsidwire ntchito kupititsa patsogolo matenda, chithandizo ndi matenda. Kusayenda bwino kumeneku kumakhala pang'onopang'ono chifukwa cha chikhalidwe ndi kusiyanasiyana kwa kuvutika maganizo, mogwirizana ndi kusiyanasiyana kwa njira m'mabuku ofufuza komanso magulu ambiri a biomarkers omwe ali ndi kuthekera, zomwe nthawi zambiri zimasiyana malinga ndi zifukwa zambiri. Timawonanso zolemba zomwe zilipo, zomwe zimasonyeza kuti zizindikiro zomwe zimakhudzidwa ndi kutupa, neurotrophic ndi kagayidwe kachakudya, komanso zigawo za neurotransmitter ndi neuroendocrine system, zimayimira ofuna kulonjeza kwambiri. Izi zikhoza kuyesedwa kupyolera mu majini ndi epigenetic, transcriptomic ndi proteomic, metabolomic ndi neuroimaging assessments. Kugwiritsa ntchito njira zatsopano komanso mapulogalamu ofufuza mwadongosolo tsopano akufunika kuti adziwe ngati, ndi ma biomarkers angagwiritsidwe ntchito kulosera kuyankha kwamankhwala, stratify odwala ku chithandizo chapadera ndikukhazikitsa zolinga za njira zatsopano zothandizira. Timatsimikiza kuti pali malonjezo ambiri ochepetsa kupsinjika maganizo popititsa patsogolo ndi kukulitsa njira zofufuzirazi.
Zothandizira:
Kuwunika kwa odwala omwe ali ndi ululu wosatha�EJ Dansiet ndi DC Turk*t�
Zotupa zotupa za ululu wochepa wammbuyo ndi kuchepa kwa disc: kuwunika.
Khan AN1, Jacobsen HE2, Khan J1, Filippi CG3, Levine M3, Lehman RA Jr2,4, Riew KD2,4, Lenke LG2,4, Chahine NO2,5.
Ma Biomarkers a Chronic Neuropathic Pain ndi Kugwiritsa Ntchito Kwawo Kuthekera Kwa Spinal Cord Stimulation: Ndemanga
Chibueze D. Nwagwu, 1 Christina Sarris, MD, 3 Yuan-Xiang Tao, Ph.D., MD, 2 and Antonios Mammis, MD1,2
Ma Biomarker for Depression: zidziwitso zaposachedwa, zovuta zomwe zikuchitika komanso ziyembekezo zamtsogolo. Strawbridge R1, Young AH1,2, Cleare AJ1,2.
Kupweteka kosalekeza sikumangokhudza gawo limodzi la malingaliro, makamaka, kungayambitse kusintha kwa magawo ambiri aubongo, omwe ambiri amakhudzidwa ndi machitidwe ndi magwiridwe antchito ambiri. Kafukufuku wosiyanasiyana pazaka zambiri apeza kusintha kwa hippocampus, komanso kuchepa kwa imvi kuchokera ku dorsolateral prefrontal cortex, amygdala, brainstem ndi right insular cortex, kutchula ochepa, okhudzana ndi ululu wosatha. Kuwonongeka kwa magawo angapo a zigawozi ndi ntchito zake zofananira zingathandize kuyika kusintha kwa ubongo kumeneku, kwa anthu ambiri omwe ali ndi ululu wosatha. Cholinga cha nkhani yotsatirayi ndikuwonetsa komanso kukambirana za kusintha kwa ubongo ndi ntchito zomwe zimagwirizanitsidwa ndi ululu wosaneneka, makamaka ngati zomwe zikuwonetsa mwina sizikuwonongeka kapena atrophy.
Kupweteka kosatha kumawoneka kuti kumalumikizidwa ndi kuchepa kwa imvi muubongo m'malo omwe amapatsirana zowawa. Mapangidwe a morphological omwe amayambitsa kusintha kwamapangidwe awa, mwina kutsatira kukonzanso kwa magwiridwe antchito komanso pulasitiki yapakati muubongo, sizikudziwika. Kupweteka kwa m'chiuno osteoarthritis ndi amodzi mwa ma syndromes opweteka omwe amatha kuchiritsidwa. Tinafufuza odwala 20 omwe ali ndi ululu wosatha chifukwa cha unilateral coxarthrosis (zaka zapakati pa 63.25�9.46 (SD) zaka, 10 akazi) pamaso pa opaleshoni ya chiuno cha endoprosthetic (pain state) ndikuyang'anira kusintha kwa ubongo mpaka chaka chimodzi pambuyo pa opaleshoni: masabata a 1�6. , masabata 8�12 ndi miyezi 18�10 pamene palibe ululu. Odwala omwe amamva kupweteka kosalekeza chifukwa cha unilateral coxarthrosis anali ndi imvi yocheperako poyerekeza ndi zowongolera mu anterior cingulate cortex (ACC), insular cortex ndi operculum, dorsolateral prefrontal cortex (DLPFC) ndi orbitofrontal cortex. Zigawozi zimagwira ntchito monga machitidwe ambiri ophatikizana panthawi yachidziwitso komanso kuyembekezera zowawa. Odwalawo atamva ululu atachira pambuyo pa opaleshoni ya endoprosthetic, kuwonjezeka kwa imvi m'madera omwewo kunapezeka. Tidapezanso kuchulukirachulukira kwa imvi muubongo mu premotor cortex ndi malo owonjezera agalimoto (SMA). Timatsimikiza kuti imvi zowawa mu ululu wosatha sizomwe zimayambitsa, koma zachiwiri ku matendawa ndipo zimakhala zochepa chifukwa cha kusintha kwa magalimoto ndi kugwirizanitsa thupi.
Introduction
Umboni wa kukonzanso magwiridwe antchito ndi makonzedwe a odwala opweteka kwambiri amachirikiza lingaliro lakuti kupweteka kosalekeza sikuyenera kuganiziridwa ngati kusintha kwa ntchito, komanso chifukwa cha ubongo wogwira ntchito komanso wopangidwa ndi ubongo [1], [2], [3], [4], [5], [6]. M'zaka zisanu ndi chimodzi zapitazi, maphunziro opitilira 20 adasindikizidwa akuwonetsa kusintha kwaubongo mu 14 syndromes opweteka kwambiri. Chochititsa chidwi pa maphunziro onsewa ndi chakuti kusintha kwa imvi sikunagawidwe mwachisawawa, koma kumachitika m'madera odziwika bwino a ubongo � ndiko, kutenga nawo mbali mu supraspinal nociceptive processing. Zofukufuku zodziwika kwambiri zinali zosiyana pa ululu uliwonse wa ululu, koma umakhala mu cingulate cortex, orbitofrontal cortex, insula ndi dorsal pons [4]. Zina mwazinthu zimaphatikizapo thalamus, dorsolateral prefrontal cortex, basal ganglia ndi dera la hippocampal. Zomwe zapezazi nthawi zambiri zimakambidwa ngati ma cell atrophy, kulimbikitsa lingaliro la kuwonongeka kapena kutayika kwa ubongo wa imvi [7], [8], [9]. M'malo mwake, ofufuza adapeza kulumikizana pakati pa imvi yaubongo kumachepa komanso nthawi ya ululu [6], [10]. Koma nthawi ya ululu imalumikizidwanso ndi zaka za wodwalayo, komanso zaka zomwe zimadalira padziko lonse lapansi, komanso kuchepa kwapadera kwa imvi kumalembedwa bwino [11]. Kumbali ina, kusintha kwapangidwe kumeneku kungakhalenso kuchepa kwa kukula kwa maselo, madzi owonjezera, synaptogenesis, angiogenesis kapena chifukwa cha kusintha kwa magazi [4], [12], [13]. Kaya gwero liri lotani, chifukwa cha kutanthauzira kwathu kwa zomwe tapeza ndikofunikira kuti tiwone zomwe zapezedwazi potengera kuchuluka kwa maphunziro a morphometric muzochita zolimbitsa thupi zomwe zimadalira pulasitiki, popeza kusintha kwaubongo komwe kumachitika m'chigawocho kwawonetsedwa mobwerezabwereza potsatira chidziwitso ndi masewera olimbitsa thupi [ 14].
Sizikudziwika chifukwa chake anthu ochepa chabe amakhala ndi matenda opweteka kwambiri, poganizira kuti ululu ndizochitika padziko lonse. Funso limakhala ngati mwa anthu ena kusiyana kwapangidwe pakati pa machitidwe opatsirana ululu kungakhale ngati diathesis ya ululu wosatha. Imvi imasintha mu ululu wa phantom chifukwa cha kudulidwa [15] ndi kuvulala kwa msana [3] zimasonyeza kuti kusintha kwa morphological kwa ubongo ndi, mwina, chifukwa cha ululu wosatha. Komabe, ululu wa m'chiuno osteoarthritis (OA) ndi amodzi mwa ochepa matenda opweteka omwe amatha kuchiritsidwa, monga 88% mwa odwalawa nthawi zonse samva ululu potsatira opaleshoni yonse ya chiuno (THR) [16]. Mu kafukufuku woyendetsa ndege tasanthula odwala khumi omwe ali ndi chiuno cha OA asanachite opaleshoni komanso atangomaliza kumene. Tinapeza kuchepa kwa imvi mu anterior cingulated cortex (ACC) ndi insula panthawi ya ululu wosatha opaleshoni ya THR isanachitike ndipo tinapeza kuwonjezeka kwa imvi m'madera a ubongo omwe amamva ululu pambuyo pa opaleshoni [17]. Poyang'ana zotsatirazi, tsopano tinakulitsa maphunziro athu ofufuza odwala ambiri (n? =? 20) pambuyo pa THR yopambana ndikuyang'anira kusintha kwa ubongo kwa nthawi zinayi, mpaka chaka chimodzi pambuyo pa opaleshoni. Kuti tiwongolere kusintha kwa imvi chifukwa chakusintha kwagalimoto kapena kupsinjika, tidaperekanso mafunso okhudza kuwongolera magwiridwe antchito agalimoto ndi thanzi lamaganizidwe.
Zida ndi njira
Odzipereka
Odwala omwe adanenedwa pano ndi gulu la odwala 20 mwa odwala 32 omwe adasindikizidwa posachedwa omwe adafanizidwa ndi gulu lowongolera thanzi la zaka komanso jenda [17] koma adachita nawo kafukufuku wotsatira wa chaka chimodzi. Pambuyo pa opaleshoni odwala 12 anasiya chifukwa cha opaleshoni yachiwiri ya endoprosthetic (n?=?2), matenda aakulu (n?=?2) ndi kuchotsedwa kwa chilolezo (n?=?8). Izi zidasiya gulu la odwala makumi awiri omwe ali ndi unilateral primary hip OA (nthawi yayitali 63.25�9.46 (SD) zaka, 10 akazi) omwe adafufuzidwa kanayi: asanachite opaleshoni (pain state) komanso 6�8 ndi 12�18 masabata ndi 10 �Miyezi 14 pambuyo pa opareshoni ya endoprosthetic, pomwe ululu wopanda chilichonse. Odwala onse omwe ali ndi chiuno chachikulu cha OA anali ndi mbiri yopweteka kwambiri kuposa miyezi ya 12, kuyambira 1 mpaka zaka 33 (kutanthauza zaka 7.35) ndi chiwerengero cha ululu wa 65.5 (kuchokera ku 40 mpaka 90) pazithunzi za analogue (VAS) kuyambira 0 (palibe zowawa) mpaka 100 (zowawa zoyipitsitsa). Tinayesa zochitika zilizonse zowawa zazing'ono, kuphatikizapo dzino-, khutu- ndi mutu mpaka masabata a 4 musanayambe phunzirolo. Tidasankhanso mwachisawawa zambiri kuchokera ku 20 kugonana- ndi zaka zofananira zowongolera zathanzi (zaka zapakati pa 60,95�8,52 (SD) zaka, 10 akazi) pa 32 ya kafukufuku woyendetsa omwe tawatchulawa [17]. Palibe odwala 20 kapena 20 ogonana- ndi zaka zofanana ndi odzipereka athanzi omwe anali ndi mbiri yachipatala kapena yamkati. Kafukufukuyu anavomerezedwa ndi komiti ya Ethics m'deralo ndipo chilolezo cholembedwa chinapezedwa kuchokera kwa onse omwe adachita nawo kafukufuku asanayesedwe.
Deta Yamakhalidwe
Tinasonkhanitsa deta yokhudzana ndi kuvutika maganizo, somatization, nkhawa, ululu ndi thanzi labwino la thupi ndi maganizo kwa odwala onse ndi nthawi zonse zinayi pogwiritsa ntchito mafunso otsatirawa: Beck Depression Inventory (BDI) [18], Brief Symptom Inventory (BSI) [19], Schmerzempfindungs-Skala (SES?=?pain unpleasantness scale) [20] and Health Survey 36-Item Short Form (SF-36) [21] ndi Nottingham Health Profile (NHP). Tidachita mobwerezabwereza ANOVA ndikuphatikiza ma t-mayeso a michira iwiri kuti tifufuze deta yotalikirapo yamakhalidwe pogwiritsa ntchito SPSS 13.0 ya Windows (SPSS Inc., Chicago, IL), ndikugwiritsa ntchito kukonza kwa Greenhouse Geisser ngati lingaliro la sphericity linaphwanyidwa. Mulingo wofunikira udayikidwa pa p<0.05.
VBM - Kupeza Data
Chithunzi chopeza. Kujambula kwapamwamba kwa MR kunkachitika pa 3T MRI system (Siemens Trio) yokhala ndi mutu wamtundu wa 12. Pazigawo zinayi zilizonse, jambulani I (pakati pa tsiku limodzi ndi mwezi wa 1 musanayambe opaleshoni ya endoprosthetic), jambulani II (masabata 3 mpaka 6 mutatha opaleshoni), jambulani III (masabata 8 mpaka 12 mutatha opaleshoni) ndi kujambula IV (18�10) miyezi atachitidwa opaleshoni), MRI yolemetsa ya T14 idapezedwa kwa wodwala aliyense pogwiritsa ntchito 1D-FLASH sequence (TR 3 ms, TE 15 ms, flip angle 4.9�, 25 mm magawo, FOV 1�256, voxel size 256�1� 1 mm).
Kukonza Zithunzi ndi Kusanthula Mawerengero
Kukonzekera ndi kusanthula deta kunachitika ndi SPM2 (Wellcome Department of Cognitive Neurology, London, UK) yomwe ikuyenda pansi pa Matlab (Mathworks, Sherborn, MA, USA) ndipo inali ndi bokosi lachida la voxel-based morphometry (VBM) la data longitudinal, zimachokera pazithunzi zapamwamba za 3D MR ndipo zimalola kugwiritsa ntchito ziwerengero zanzeru za voxel kuti zizindikire kusiyana kwamadera mu kachulukidwe kazinthu zotuwa kapena ma voliyumu [22], [23]. Mwachidule, kukonza kusanachitike kunkakhudza kukhazikika kwa malo, magawo a imvi ndi kusalaza kwapakati kwa 10 mm ndi kernel ya Gaussian. Pamasitepe okonzekeratu, tidagwiritsa ntchito ndondomeko yokhathamiritsa [22], [23] ndi scanner- ndi template yophunzirira yeniyeni ya imvi [17]. Tidagwiritsa ntchito SPM2 osati SPM5 kapena SPM8 kuti kusanthula uku kufanane ndi kafukufuku wathu woyendetsa ndege [17]. chifukwa amalola normalization kwambiri ndi segmentation wa deta longitudinal. Komabe, pomwe zosintha zaposachedwa za VBM (VBM8) zidapezeka posachedwa (dbm.neuro.uni-jena.de/vbm/), tidagwiritsanso ntchito VBM8.
Cross-Sectional Analysis
Tinagwiritsa ntchito mayeso awiri a T-0.001 kuti tipeze kusiyana kwa zigawo mu utoto wa imvi pakati pamagulu (odwala nthawi yayitali) komanso kuwongolera kwathanzi). Tinagwiritsira ntchito pakhomo la p <9 (osakonzedwa) kudutsa mu ubongo wonse chifukwa cha mphamvu yathu yamphamvu, yomwe imachokera ku maphunziro odziimira a 7 ndi magulu omwe akuwonetsa kuchepa kwa imvi kwa odwala opweteka kwambiri [8], [9], [ [Chithunzi patsamba 15]. 24], [Chithunzi patsamba 25]. ). Maguluwa adafananizidwa zaka ndi kugonana popanda kusiyana kwakukulu pakati pa magulu. Kuti tifufuze ngati kusiyana pakati pa magulu atasintha patatha chaka chimodzi, tinali ofanana ndi odwala pofika nthawi yayitali.
Longitudinal Analysis
Kuti tipeze kusiyana pakati pa nthawi (Scan I�IV) tinayerekeza zojambulazo musanachite opaleshoni (pain state) komanso masabata a 6�8 ndi 12�18 ndi miyezi 10�14 pambuyo pa opaleshoni ya endoprosthetic (yopanda ululu) monga muyeso wobwerezabwereza ANOVA. Chifukwa ubongo uliwonse umasintha chifukwa cha ululu wopweteka kwambiri ungafunike nthawi kuti ubwerere pambuyo pa opaleshoni ndi kutha kwa ululu komanso chifukwa cha ululu wa opaleshoni pambuyo pa opaleshoni yomwe odwala adanena, tinafanizira mu kufufuza kwautali I ndi II ndi scan III ndi IV. Kuti tipeze kusintha komwe sikunagwirizane kwambiri ndi ululu, tinayang'ananso kusintha kwapang'onopang'ono pakapita nthawi. Tinatembenuza ubongo wa odwala omwe ali ndi OA ya chiuno chakumanzere (n? =? 7) kuti tikhale okhazikika kumbali ya ululu kwa onse awiri, kuyerekezera kwa gulu ndi kusanthula kwautali, koma makamaka kusanthula deta yosasinthika. Tidagwiritsa ntchito mphambu ya BDI ngati covariate pachitsanzocho.
Results
Dongosolo la Chikhalidwe
Odwala onse adanena kuti kupweteka kwa m'chiuno kusanachitike opaleshoni ndipo sanamve ululu (ponena za ululu wosaneneka) atangochitidwa opaleshoni, koma adanena kuti ululu wopweteka kwambiri pambuyo pa opaleshoniyo pa scan II zomwe zinali zosiyana ndi zowawa chifukwa cha osteoarthritis. Zotsatira za umoyo wamaganizo za SF-36 (F(1.925/17.322)?=?0.352, p?=?0.7) ndi BSI global score GSI (F(1.706/27.302)?=?3.189, p?=?0.064 ) sanawonetse kusintha pa nthawi ya nthawi komanso kusagwirizana ndi maganizo. Palibe zowongolera zomwe zidawonetsa kupweteka kwanthawi yayitali kapena kosalekeza ndipo palibe yemwe adawonetsa zizindikiro za kukhumudwa kapena kulumala kwakuthupi / m'maganizo.
Opaleshoni isanachitike, odwala ena amawonetsa kukhumudwa pang'ono mpaka pang'ono m'magulu a BDI omwe adatsika kwambiri pa scan III (t(17)?=?2.317, p?=?0.033) ndi IV (t(16)?=?2.132, p? =?0.049). Kuphatikiza apo, ziwerengero za SES (zosasangalatsa zowawa) za odwala onse zidasintha kwambiri kuchokera ku scan I (asanachite opareshoni) kuti ajambule II (t(16)?=?4.676, p<0.001), scan III (t(14)?=? 4.760, p<0.001) ndi scan IV (t (14)?=?4.981, p<0.001, 1 chaka pambuyo pa opaleshoni) pamene kusasangalatsa kwa ululu kunachepa ndi kupweteka kwambiri. Zowawa pa scan 1 ndi 2 zinali zabwino, mlingo womwewo pa tsiku 3 ndi 4 zoipa. SES imangofotokoza ubwino wa ululu womwe umamveka. Choncho zinali zabwino pa tsiku 1 ndi 2 (kutanthauza 19.6 pa tsiku 1 ndi 13.5 pa tsiku 2) ndi zoipa (na) pa tsiku 3 & 4. Komabe, odwala ena sanamvetse njirayi ndipo amagwiritsa ntchito SES monga � khalidwe lapadziko lonse. ya moyo� muyeso. Ichi ndichifukwa chake odwala onse adafunsidwa tsiku lomwelo payekha komanso ndi munthu yemweyo ponena za zowawa.
Mu kafukufuku wachidule wa zaumoyo (SF-36), womwe uli ndi mfundo zachidule za Physical Health Score ndi Mental Health Score [29], odwalawo adachita bwino kwambiri pamlingo wa Physical Health kuchokera pa scan I mpaka scan II (t( 17)?=??4.266, p?=?0.001), jambulani III (t(16)?=??8.584, p<0.001) ndi IV (t(12)?=??7.148, p<0.001), koma osati mu Mental Health Score. Zotsatira za NHP zinali zofanana, mu subscale �pain� (reversed polarity) tinawona kusintha kwakukulu kuchokera ku scan I kupita ku scan II (t(14)?=??5.674, p<0.001, scan III (t(12) )?=??7.040, p<0.001 ndi sikani IV (t(10)?=??3.258, p?=?0.009). Tinapezanso kuwonjezeka kwakukulu kwapang'onopang'ono �kusuntha kwathupi� kuchokera pa scan I kupita ku sikani III (t(12)?=??3.974, p?=?0.002) ndi sikani IV (t(10)?=??2.511, p?=?0.031). Panalibe kusintha kwakukulu pakati pa sikani I ndi sikani II ( masabata asanu ndi limodzi pambuyo pa opaleshoni).
Structural Data
Kusanthula kwamagulu. Tinaphatikizapo zaka monga covariate mu chitsanzo cha mzere wamba ndipo sitinapeze zosokoneza zaka. Poyerekeza ndi maulamuliro okhudzana ndi kugonana ndi msinkhu, odwala omwe ali ndi chiuno chachikulu cha OA (n? =? DLPFC), pole yanthawi yakumanja ndi cerebellum (Table 20 ndi Chithunzi 1). Kupatulapo putamen yoyenera (x?=?1, y?=??31, z?=??14; p<1, t?=?0.001) palibe kuwonjezeka kwakukulu kwa kachulukidwe ka imvi komwe kunapezeka mwa odwala OA poyerekeza kumawongolera athanzi. Poyerekeza odwala panthawi ya scan IV ndi zowongolera zofananira, zotsatira zomwezo zidapezeka monga pakuwunika kwapakatikati pogwiritsa ntchito scan I poyerekeza ndi zowongolera.
Chithunzi 1: Mapu owerengetsera owerengera omwe akuwonetsa kusiyana kwa mapangidwe a imvi kwa odwala omwe ali ndi ululu wopweteka chifukwa cha chiuno chachikulu cha OA poyerekeza ndi zowongolera komanso motalika poyerekeza ndi iwowo pakapita nthawi. Kusintha kwakukulu kwa imvi kumawonetsedwa mumtundu wapamwamba, deta yapakatikati imawonetsedwa muzofiira ndi zazitali zazitali zachikasu. Ndege ya Axial: Kumanzere kwa chithunzi ndi kumanzere kwa ubongo. pamwamba: Madera a kuchepa kwakukulu kwa imvi pakati pa odwala omwe ali ndi ululu wosatha chifukwa cha chiuno chachikulu cha OA ndi maphunziro osakhudzidwa. p<0.001 pansi osakonzedwa: Kuwonjezeka kwa Grey kwa odwala 20 opanda ululu pa nthawi yachitatu ndi yachinayi yojambula pambuyo pa opaleshoni yonse ya m'chiuno, poyerekeza ndi yoyamba (preoperative) ndi yachiwiri (masabata a 6�8 pambuyo pa opaleshoni). p<0.001 Mapulani Osakonzedwa: Kuyerekeza kuyerekezera ndi 90% nthawi yachidaliro, zotsatira zachiwongola dzanja, mayunitsi osagwirizana. x-axis: kusiyanitsa kwa 4 timepoints, y-axis: kuyerekezera kosiyana pa ?3, 50, 2 kwa ACC ndi kuyerekezera kwa 36, 39, 3 kwa insula.
Kutembenuza deta ya odwala omwe ali ndi chiuno chakumanzere OA (n?=?7) ndi kuwafanizira ndi machitidwe abwino sikunasinthe zotsatira zake kwambiri, koma kuchepa kwa thalamus (x?=?10, y?=??20, z =?3, p<0.001, t?=?3.44) ndi kuwonjezeka kwa cerebellum yoyenera (x?=?25, y?=??37, z?=??50, p<0.001, t? =? 5.12) zomwe sizinafikire kufunikira kwa deta yosasinthika ya odwala poyerekeza ndi zowongolera.
Kusanthula kwautali. Pakufufuza kwa nthawi yayitali, kuwonjezeka kwakukulu (p <.001 osakonzedwa) kwa imvi kunazindikirika poyerekezera ndi kujambula koyamba ndi kwachiwiri (kupweteka kwapang'onopang'ono / kupweteka kwapambuyo kwa opaleshoni) ndi scan yachitatu ndi yachinayi (yopanda ululu) mu ACC, insular cortex, cerebellum ndi pars orbitalis mwa odwala omwe ali ndi OA (Table 2 ndi Chithunzi 1). Imvi inachepa pakapita nthawi (p<.001 kusanthula konse kwa ubongo kosakonzedwa) mu sekondale somatosensory cortex, hippocampus, midcingulate cortex, thalamus ndi caudate nucleus kwa odwala OA (Chithunzi 2).
Chithunzi 2: a) Kuwonjezeka kwakukulu kwa imvi ya ubongo pambuyo pochita bwino. Kuwona kwa axial kwa kuchepa kwakukulu kwa imvi kwa odwala omwe ali ndi ululu wosatha chifukwa cha chiuno chachikulu cha OA poyerekeza ndi maphunziro olamulira. p<0.001 yosakonzedwa (kusanthula kwagawo), b) Kutalika kwakutali kwa imvi kwakanthawi kokangana chithunzi i & ICaCAN III> Scan IV) kwa odwala omwe ali ndi OA. P <0.001 Osavomerezeka (Kusanthulika Kwa Tizikulu). Mbali yakumanzere ya chithunzicho ndi mbali yakumanzere ya ubongo.
Kutembenuza deta ya odwala omwe ali ndi chiuno chakumanzere OA (n?=?7) sikunasinthe zotsatira zake kwambiri, koma kuchepa kwa ubongo wa imvi mu Heschl's Gyrus (x?=??41, y?=?? 21, z?=?10, p<0.001, t?=?3.69) ndi Precuneus (x?=?15, y?=??36, z?=?3, p<0.001, t?=?4.60) .
Posiyanitsa scanner yoyamba (presurgery) ndi scans 3 + 4 (postsurgery), tinapeza kuwonjezeka kwa imvi ku frontal cortex ndi motor cortex (p <0.001 osakonzedwa). Tikuwona kuti kusiyanitsa kumeneku kumakhala kovutirapo chifukwa tili ndi masikelo ochepa pa chikhalidwe chilichonse (kupweteka motsutsana ndi ululu). Tikatsitsa pakhomo timabwereza zomwe tapeza pogwiritsa ntchito kusiyana kwa 1 + 2 vs. 3 + 4.
Poyang'ana madera omwe amawonjezeka nthawi zonse, tapeza kusintha kwa ubongo wa imvi m'madera oyendetsa galimoto (dera la 6) kwa odwala omwe ali ndi coxarthrosis akutsatira m'malo mwa chiuno chonse (scan Idbm.neuro.uni-jena.de/vbm/) titha kubwereza zomwe tapezazi m'kati mwa cingate cortex komanso kumbuyo kwa insulae.
Tinawerengera kukula kwa zotsatira ndi kusanthula kwa magawo (odwala motsutsana ndi zowongolera) kunapereka Cohen�sd ya 1.78751 mu voxel yapamwamba ya ACC (x?=??12, y?=?25, z?=?? 16). Tidawerengeranso Cohen�sd pakuwunika kwa nthawi yayitali (kusiyanitsa jambulani 1+2 vs. scan 3+4). Izi zidapangitsa kuti Cohen�sd ya 1.1158 mu ACC (x?=??3, y?=?50, z?=?2). Ponena za insula (x?=??33, y?=?21, z?=?13) komanso zokhudzana ndi kusiyana komweko, Cohen�sd ndi 1.0949. Kuphatikiza apo, tidawerengera tanthauzo la ma voxel osakhala a ziro a mapu a Cohen�sd mkati mwa ROI (yomwe ili ndi gawo lakunja la cingulate gyrus ndi subcallosal cortex, yochokera ku Harvard-Oxford Cortical Structural Atlas): 1.251223.
Kuzindikira kwa Dr. Alex Jimenez
Odwala opweteka kwambiri amatha kukhala ndi zovuta zosiyanasiyana zaumoyo pakapita nthawi, kupatulapo zizindikiro zawo zofooketsa kale. Mwachitsanzo, anthu ambiri amakumana ndi vuto la kugona chifukwa cha ululu wawo, koma koposa zonse, kupweteka kosalekeza kumatha kubweretsanso zovuta zosiyanasiyana zamaganizidwe, kuphatikiza nkhawa ndi kukhumudwa. Zotsatira zomwe ululu ukhoza kukhala nazo pa ubongo zingawoneke ngati zovuta kwambiri koma umboni wochuluka umasonyeza kuti kusintha kwa ubongo kumeneku sikokhazikika ndipo kungathe kusinthidwa pamene odwala opweteka kwambiri akulandira chithandizo choyenera pazochitika zawo zaumoyo. Malinga ndi nkhaniyi, zovuta za imvi zomwe zimapezeka mu ululu wosatha siziwonetsa kuwonongeka kwa ubongo, koma ndizotsatira zosinthika zomwe zimakhala bwino pamene ululuwo ukuchiritsidwa mokwanira. Mwamwayi, njira zosiyanasiyana zochiritsira zilipo kuti zithandize kuchepetsa zizindikiro za ululu wosatha ndikubwezeretsanso mapangidwe ndi ntchito za ubongo.
Kukambirana
Kuyang'anira kapangidwe kaubongo wonse pakapita nthawi, timatsimikizira ndikukulitsa deta yathu yoyendetsa yomwe idasindikizidwa posachedwa [17]. Tinapeza kusintha kwa ubongo wa imvi kwa odwala omwe ali ndi chiuno chachikulu cha osteoarthritis mu chikhalidwe chopweteka kwambiri, chomwe chimasintha pang'ono pamene odwalawa sakumva ululu, potsatira opaleshoni ya chiuno cha endoprosthetic. Kuwonjezeka pang'ono kwa imvi pambuyo pa opaleshoni kuli pafupi ndi madera omwe kuchepa kwa imvi kumawonekera pamaso pa opaleshoni. Kutembenuza zidziwitso za odwala omwe ali ndi chiuno chakumanzere OA (ndichifukwa chake kukhazikika kwa mbali ya ululu) kunali ndi zotsatira zochepa chabe pa zotsatira koma kumasonyezanso kuchepa kwa imvi mu Heschl's gyrus ndi Precuneus zomwe sitingathe kuzifotokoza mosavuta, popeza palibe lingaliro lachiyambi lomwe liripo, samalani kwambiri. Komabe, kusiyana komwe kumawonedwa pakati pa odwala ndi kuwongolera kwathanzi pa sikani ndidawonekerabe pakuwunika kwapang'onopang'ono pa scan IV. Kuwonjezeka kwapang'onopang'ono kwa imvi pakapita nthawi ndikosavuta, mwachitsanzo, sikuli kosiyana mokwanira kukhala ndi zotsatira pakuwunika kwa gawo, zomwe zawonetsedwa kale m'maphunziro ofufuza za pulasitiki yodalirika [30], [31]. Timazindikira kuti chifukwa chakuti timawonetsa mbali zina za ubongo-kusintha chifukwa cha ululu wosatha kuti utembenuke sikumapatula kuti mbali zina za kusintha kumeneku sizingatheke.
Chochititsa chidwi n'chakuti, tinawona kuti imvi imachepa mu ACC mu odwala opweteka kwambiri opaleshoni isanayambe kupitirira masabata a 6 pambuyo pa opaleshoni (scan II) ndipo imangowonjezera ku scan III ndi IV, mwina chifukwa cha ululu wa pambuyo pa opaleshoni, kapena kuchepa kwa galimoto. ntchito. Izi zikugwirizana ndi chidziwitso cha khalidwe la masewera olimbitsa thupi omwe akuphatikizidwa mu NHP, yomwe pambuyo pa opaleshoni sinasonyeze kusintha kwakukulu pa nthawi ya II koma inawonjezeka kwambiri ku scan III ndi IV. Zindikirani, odwala athu adanena kuti palibe ululu m'chiuno pambuyo pa opaleshoni, koma adamva ululu pambuyo pa opaleshoni mu minofu yozungulira ndi khungu zomwe zinkawoneka mosiyana kwambiri ndi odwala. Komabe, monga odwala adakali ndi ululu wopweteka pa scan II, tinasiyanitsanso jambulani choyamba (pre-opareshoni) ndi ma scans III + IV (opaleshoni yapambuyo), kuwonetsa kuwonjezeka kwa imvi kutsogolo kwa cortex ndi motor cortex. Tikuwona kuti kusiyanitsa kumeneku kumakhala kovutirapo kwambiri chifukwa chosayang'ana pang'ono pa chikhalidwe chilichonse (kupweteka ndi kusapweteka). Pamene tidatsitsa pakhomo timabwereza zomwe tapeza pogwiritsa ntchito kusiyana kwa I + II vs. III + IV.
Deta yathu imasonyeza kuti kusintha kwa imvi kwa odwala opweteka kwambiri, omwe nthawi zambiri amapezeka m'madera omwe amagwiritsidwa ntchito mu supraspinal nociceptive processing [4] si chifukwa cha neuronal atrophy kapena kuwonongeka kwa ubongo. Mfundo yakuti kusintha kumeneku komwe kumawoneka muzochitika zowawa zosasintha sikungasinthe kotheratu kungafotokozedwe ndi nthawi yochepa yowonera (chaka chimodzi pambuyo pa opaleshoni poyerekeza ndi zaka zisanu ndi ziwiri za ululu wosatha usanayambe opaleshoni). Kusintha kwaubongo wa Neuroplastic komwe mwina kwachitika zaka zingapo (monga chotsatira cha kulowetsedwa kosalekeza) kumafunikira nthawi yochulukirapo kuti asinthe. Kuthekera kwina chifukwa chake kuwonjezereka kwa imvi kumatha kudziwika muzolemba zautali koma osati pazigawo zodutsamo (ie pakati pa magulu pa nthawi ya IV) ndikuti chiwerengero cha odwala (n?=?20) ndi chochepa kwambiri. Ziyenera kunenedwa kuti kusiyana pakati pa ubongo wa anthu angapo ndi kwakukulu kwambiri komanso kuti deta yotalikirapo ili ndi ubwino wakuti kusiyanako ndi kochepa chifukwa ubongo womwewo umasinthidwa kangapo. Chifukwa chake, zosintha zosawoneka bwino zitha kuwoneka mu data yautali [30], [31], [32]. Zachidziwikire, sitinganene kuti zosinthazi sizingasinthidwe pang'ono ngakhale kuti sizokayikitsa, chifukwa cha zomwe zapezeka pochita masewera olimbitsa thupi komanso kukonzanso bwino [4], [12], [30], [33], [34]. Kuti tiyankhe funsoli, maphunziro amtsogolo ayenera kufufuza odwala mobwerezabwereza kwa nthawi yayitali, mwina zaka.
Tikuwona kuti titha kupanga malingaliro ochepa okhudzana ndi kusintha kwaubongo wa morphological pakapita nthawi. Chifukwa chake ndi chakuti pomwe tidapanga kafukufukuyu mu 2007 ndikusanthula mu 2008 ndi 2009, sizinadziwike ngati kusintha kwamapangidwe kungachitike ndipo chifukwa chotheka tidasankha masiku ndi nthawi yojambula monga tafotokozera apa. Wina angatsutse kuti imvi imasintha nthawi, yomwe timafotokozera gulu la odwala, zikhoza kuchitika mu gulu lolamulira komanso (nthawi zotsatira). Komabe, kusintha kulikonse chifukwa cha ukalamba, ngati kuli kotheka, kungayembekezere kuchepa kwa voliyumu. Chifukwa cha lingaliro lathu la priori, lochokera ku maphunziro odziimira a 9 ndi magulu omwe amasonyeza kuchepa kwa imvi kwa odwala opweteka kwambiri [7], [8], [9], [15], [24], [25], [26], [27], [28], tidayang'ana kwambiri pakuwonjezeka kwa madera pakapita nthawi ndipo tikukhulupirira kuti kupeza kwathu sikukhala kophweka kwa nthawi. Zindikirani, sitinganene kuti imvi imachepa pakapita nthawi yomwe tapeza mu gulu lathu la odwala ikhoza kukhala chifukwa cha nthawi, chifukwa sitinayang'ane gulu lathu lolamulira nthawi yomweyo. Chifukwa cha zomwe zapezedwa, maphunziro amtsogolo akuyenera kukhala ndi nthawi yayitali komanso yayifupi, chifukwa chochita masewera olimbitsa thupi motengera kusintha kwaubongo kwa morphometric kumatha kuchitika mwachangu ngati sabata la 1 [32], [33].
Kuphatikiza pa kukhudzidwa kwa gawo la nociceptive la ululu pa ubongo wa imvi [17], [34] tinawona kuti kusintha kwa kayendetsedwe ka galimoto mwinamwake kumapangitsanso kusintha kwapangidwe. Tinapeza madera a magalimoto ndi ma premotor (dera la 6) kuti achuluke nthawi zonse (Chithunzi 3). Mwachidziwitso izi zitha kukhala chifukwa chakuyenda bwino kwa magalimoto pakapita nthawi popeza odwalawo analibenso malire pakukhala ndi moyo wabwinobwino. Makamaka ife sitinayang'ane pa ntchito yamagalimoto koma kusintha kwa zowawa, chifukwa chofuna kwathu koyambirira kuti tifufuze ngati kuchepetsedwa kodziwika bwino kwa ubongo wa imvi kwa odwala omwe ali ndi ululu wosachiritsika ndikosinthika. Chifukwa chake, sitinagwiritse ntchito zida zapadera kuti tifufuze ntchito zamagalimoto. Komabe, (ntchito) kukonzanso kotekisi kwa odwala omwe ali ndi ululu wa syndromes amalembedwa bwino [35], [36], [37], [38]. Komanso, motor cortex ndi chandamale chimodzi mu njira zochiritsira za odwala opweteka osachiritsika omwe amagwiritsa ntchito kukondoweza kwa ubongo [39], [40], transcranial mwachindunji stimulation panopa [41], ndi mobwerezabwereza transcranial maginito stimulation [42], [43]. Njira zenizeni za kusinthika koteroko (kuwongolera vs. kuletsa, kapena kungosokoneza maukonde okhudzana ndi ululu) sizinadziwikebe [40]. Kafukufuku waposachedwa adawonetsa kuti chokumana nacho chamoto chimatha kusintha mawonekedwe a ubongo [13]. Synaptogenesis, kukonzanso mawonekedwe amayendedwe ndi angiogenesis mu motor cortex zitha kuchitika ndi zofuna zapadera za ntchito yamagalimoto. Tsao et al. adawonetsa kukonzanso mu motor cortex ya odwala omwe ali ndi ululu wopweteka kwambiri wammbuyo womwe umawoneka ngati ululu wammbuyo [44] ndi Puri et al. adawona kuchepetsedwa kwa kumanzere kwamtundu wa imvi kwa odwala fibromyalgia [45]. Phunziro lathu silinapangidwe kuti lisokoneze zinthu zosiyanasiyana zomwe zingasinthe ubongo mu ululu wosaneneka koma timatanthauzira deta yathu yokhudza kusintha kwa imvi kotero kuti samangowonetsa zotsatira za kulowetsa kosalekeza kosalekeza. Ndipotu, kafukufuku waposachedwapa wa odwala opweteka a neuropathic adanena za zolakwika m'madera a ubongo omwe amakhudza maganizo, odziimira okha, komanso akumva ululu, kutanthauza kuti amagwira ntchito yofunika kwambiri pa chithunzi chachipatala cha ululu wosatha [28].
Chithunzi 3: Mapu owerengera owerengera omwe akuwonetsa kuwonjezeka kwakukulu kwa imvi yaubongo m'malo amagalimoto (dera la 6) mwa odwala omwe ali ndi coxarthrosis asanafanizidwe ndi pambuyo pa THR (kuwunika kwa nthawi yayitali, jambulani I. Kuyerekezera koyerekeza ndi x?=?19, y?=??12, z?=?70.
Maphunziro awiri aposachedwapa oyendetsa ndege adayang'ana pa chithandizo cha m'chiuno mwa odwala osteoarthritis, matenda okhawo omwe amatha kupweteka kwambiri omwe amatha kuchiritsidwa ndi chiuno chonse [17], [46] ndipo detayi ili pambali ndi kafukufuku waposachedwapa wa odwala opweteka kwambiri [ 47]. Maphunzirowa akuyenera kuwonedwa poyang'ana maphunziro angapo a nthawi yayitali omwe amafufuza mapulasitiki omwe amadalira chidziwitso cha neuronal mwa anthu pamlingo wapangidwe [30], [31] ndi kafukufuku waposachedwapa wokhudza kusintha kwa ubongo kwa odzipereka athanzi omwe akukumana ndi kukondoweza kowawa mobwerezabwereza [34] . Uthenga wofunikira wa maphunziro onsewa ndi wakuti kusiyana kwakukulu mu ubongo wa ubongo pakati pa odwala opweteka ndi maulamuliro akhoza kutha pamene ululu wachiritsidwa. Komabe, ziyenera kuganiziridwa kuti sizikudziwikiratu ngati kusintha kwa odwala opweteka kwambiri kumangochitika chifukwa cha kulowetsa kwa nociceptive kapena chifukwa cha zotsatira za ululu kapena zonse ziwiri. Ndizotheka kuti kusintha kwamakhalidwe, monga kulandidwa kapena kupititsa patsogolo kucheza ndi anthu, kulimba mtima, kuphunzitsa thupi ndi kusintha kwa moyo ndikokwanira kupanga ubongo [6], [12], [28], [48]. Makamaka kupsinjika maganizo monga co-morbidity kapena zotsatira za ululu ndizofunikira kwambiri kuti afotokoze kusiyana pakati pa odwala ndi maulamuliro. Kagulu kakang'ono ka odwala athu omwe ali ndi OA adawonetsa kutsika kwapang'onopang'ono mpaka kocheperako komwe kunasintha pakapita nthawi. Sitinapeze kusintha kwapangidwe kwa covary kwambiri ndi BDI-score koma funso limakhala ndi kusintha kwa makhalidwe ena angati chifukwa cha kusakhalapo kwa ululu ndi kusintha kwa magalimoto kungapangitse zotsatirazo komanso momwe amachitira. Kusintha kwa khalidwe kumeneku kungapangitse kuchepa kwa imvi mu ululu wosatha komanso kuwonjezeka kwa imvi pamene ululu wapita.
Chinthu chinanso chofunika chomwe chingasokoneze kutanthauzira kwathu kwa zotsatira zake ndi chakuti pafupifupi odwala onse omwe ali ndi ululu wopweteka amamwa mankhwala oletsa ululu, omwe amasiya pamene sanamve ululu. Wina angatsutse kuti NSAIDs monga diclofenac kapena ibuprofen zimakhala ndi zotsatira zina pa mitsempha ya mitsempha ndipo zomwezo zimakhala zowona kwa opioids, antiepileptics ndi antidepressants, mankhwala omwe amagwiritsidwa ntchito mobwerezabwereza mu ululu wosatha. Zotsatira za opha ululu ndi mankhwala ena pazopeza za morphometric zitha kukhala zofunika (48). Palibe kafukufuku mpaka pano wasonyeza zotsatira za mankhwala opweteka pa ubongo wa ubongo koma mapepala angapo adapeza kuti kusintha kwa ubongo kwa odwala opweteka kwambiri sikungofotokozedwa kokha ndi kusagwira ntchito kwa ululu [15], kapena ndi mankhwala opweteka [7], [9], [49]. Komabe, maphunziro apadera akusowa. Kufufuza kwina kuyenera kuyang'ana kusintha kwazomwe zimadalira pazidziwitso za cortical plasticity, zomwe zingakhale ndi zotsatira zachipatala pa chithandizo cha ululu wosatha.
Tinapezanso kuchepa kwa imvi pakuwunika kwautali, mwina chifukwa cha kukonzanso njira zomwe zimayenderana ndi kusintha kwa magwiridwe antchito agalimoto ndi malingaliro opweteka. Palibe chidziwitso chochepa chokhudza kusintha kwa nthawi yayitali mu ubongo wa imvi muzochitika zowawa, chifukwa chake tilibe lingaliro la kuchepa kwa imvi m'maderawa pambuyo pa opaleshoni. Teutsch et al. [25] adapeza kuwonjezeka kwa ubongo wa imvi mu somatosensory ndi midcingulate cortex mwa odzipereka athanzi omwe adakumana ndi zowawa zowawa mu protocol ya tsiku ndi tsiku kwa masiku asanu ndi atatu otsatizana. Kupeza kwa imvi kumawonjezeka potsatira kuyesa koyesa kwa nociceptive kunadutsana ndi anatomically mpaka pang'ono ndi kuchepa kwa ubongo wa imvi mu phunziro ili kwa odwala omwe anachiritsidwa ndi ululu wosatha. Izi zikutanthawuza kuti kulowetsa kwa nociceptive mwa odzipereka athanzi kumapangitsa kuti azichita masewera olimbitsa thupi modalira, monga momwe amachitira odwala omwe ali ndi ululu wosaneneka, komanso kuti kusintha kumeneku kumasintha anthu odzipereka athanzi pamene kulowetsedwa kwa nociceptive kumasiya. Chifukwa chake, kuchepa kwa imvi m'maderawa omwe amawonedwa mwa odwala omwe ali ndi OA akhoza kutanthauziridwa kuti atsatire ndondomeko yofanana: zolimbitsa thupi zimasintha kusintha kwa ubongo [50]. Monga njira yosasokoneza, MR Morphometry ndiye chida choyenera chofuna kupeza magawo a morphological a matenda, kukulitsa kumvetsetsa kwathu ubale womwe ulipo pakati pa kapangidwe kaubongo ndi magwiridwe antchito, komanso kuyang'anira chithandizo chamankhwala. Chimodzi mwazovuta zazikulu m'tsogolomu ndikusintha chida champhamvu ichi cha ma multicentre ndi machiritso ochizira opweteka osatha.
Zolepheretsa Phunziroli
Ngakhale kuti phunziroli ndilowonjezereka kwa phunziro lathu lapitalo kukulitsa deta yotsatila kwa miyezi ya 12 ndikufufuza odwala ambiri, mfundo yathu yopeza kuti kusintha kwa ubongo wa morphometric mu ululu wosatha ndi kusinthika kumakhala kosaoneka bwino. Kukula kwake kumakhala kochepa (onani pamwambapa) ndipo zotsatira zake zimayendetsedwa ndi kuchepetsedwa kwina kwa gawo la ubongo wa imvi pa nthawi ya scan 2. Tikamapatula deta kuchokera ku scan 2 (mwachindunji pambuyo pa opaleshoni) ndizofunikira kwambiri. kuwonjezeka kwa imvi ya ubongo ya motor cortex ndi front cortex imapulumuka pamtunda wa p <0.001 osakonzedwa (Table 3).
Kutsiliza
Sizingatheke kusiyanitsa kuti kusintha kwapangidwe komwe tinawona chifukwa cha kusintha kwa nociceptive input, kusintha kwa galimoto kapena kugwiritsa ntchito mankhwala kapena kusintha kwabwino monga momwemo. Kuyika gulu kusiyanitsa koyamba ndi komaliza kunawonetsa kusiyana kocheperako kuposa momwe amayembekezera. Mwachiwonekere, kusintha kwaubongo chifukwa cha kupweteka kosalekeza ndi zotsatira zonse kukukula pakapita nthawi yayitali ndipo kungafunikenso nthawi kuti abwerere. Komabe, zotsatirazi zikuwonetsa njira zakukonzanso, kuwonetsa mwamphamvu kuti kulowetsedwa kwanthawi yayitali kwa nociceptive ndi kuwonongeka kwa magalimoto mwa odwalawa kumabweretsa kusintha kosinthika m'magawo a cortical ndipo chifukwa chake kusintha kwaubongo komwe kumasinthidwa.
Kuvomereza
Tikuthokoza anthu onse odzipereka chifukwa chochita nawo kafukufukuyu komanso gulu la Physics and Methods ku NeuroImage Nord ku Hamburg. Kafukufukuyu anavomerezedwa ndi komiti ya Ethics m'deralo ndipo chilolezo cholembedwa chinapezedwa kuchokera kwa onse omwe adachita nawo kafukufuku asanayesedwe.
Ndondomeko ya Zothandizira
Ntchitoyi inathandizidwa ndi ndalama zochokera ku DFG (German Research Foundation) (MA 1862/2-3) ndi BMBF (Federal Ministry of Education and Research) (371 57 01 ndi NeuroImage Nord). Othandizira ndalama analibe gawo pakupanga maphunziro, kusonkhanitsa deta ndi kusanthula, chisankho chosindikiza, kapena kukonzekera zolembazo.
Dongosolo la Endocannabinoid: Dongosolo Lofunikira lomwe simunamvepo
Ngati simunamvepo za endocannabinoid system, kapena ECS, palibe chifukwa chochitira manyazi. Kalelo m'ma 1960, ofufuza omwe adachita chidwi ndi bioactivity ya Cannabis pamapeto pake adapatula mankhwala ake ambiri. Zinatenga zaka zina za 30, komabe, ofufuza omwe amaphunzira zinyama kuti apeze cholandirira mankhwala a ECS mu ubongo wa makoswe, kutulukira komwe kunatsegula dziko lonse lofufuza za ECS zolandilira kukhalapo komanso cholinga chawo cha thupi.
Tsopano tikudziwa kuti nyama zambiri, kuchokera ku nsomba kupita ku mbalame kupita ku zoyamwitsa, zimakhala ndi endocannabinoid, ndipo tikudziwa kuti anthu samangopanga ma cannabinoids awo omwe amalumikizana ndi dongosolo ili, komanso amapanga zinthu zina zomwe zimagwirizana ndi ECS, zomwe zimawonedwa muzomera ndi zakudya zosiyanasiyana, kupitilira mitundu ya Cannabis.
Monga dongosolo la thupi la munthu, ECS si nsanja yokhazikika ngati dongosolo lamanjenje kapena mtima. M'malo mwake, ECS ndi gulu la zolandilira zomwe zimagawidwa kwambiri mthupi lonse zomwe zimayendetsedwa kudzera mumagulu angapo omwe timawadziwa kuti endocannabinoids, kapena endogenous cannabinoids. Ma receptor otsimikizika onsewa amangotchedwa CB1 ndi CB2, ngakhale pali ena omwe adafunsidwa. PPAR ndi TRP njira zimayimiranso ntchito zina. Momwemonso, mupeza ma endocannabinoids olembedwa bwino awiri okha: anadamide ndi 2-arachidonoyl glycerol, kapena 2-AG.
Kuphatikiza apo, chofunikira pa dongosolo la endocannabinoid ndi ma enzymes omwe amapanga ndikuphwanya ma endocannabinoids. Endocannabinoids amakhulupirira kuti amapangidwa mumaziko omwe amafunikira. Ma enzymes oyambilira omwe akukhudzidwa ndi diacylglycerol lipase ndi N-acyl-phosphatidylethanolamine-phospholipase D, omwe amaphatikiza 2-AG ndi anandamide. Ma enzymes awiri omwe amawononga kwambiri ndi mafuta acid amide hydrolase, kapena FAAH, omwe amaphwanya anandamide, ndi monoacylglycerol lipase, kapena MAGL, yomwe imaphwanya 2-AG. Kuwongolera kwa ma enzyme awiriwa kumatha kuwonjezera kapena kuchepetsa kusinthika kwa ECS.
Kodi Ntchito ya ECS ndi yotani?
ECS ndiye dongosolo lalikulu la homeostatic regulatory system. Zitha kuwonedwa mosavuta ngati dongosolo lamkati la adaptogenic la thupi, nthawi zonse limagwira ntchito kuti likhale logwirizana ndi ntchito zosiyanasiyana. Endocannabinoids amagwira ntchito ngati neuromodulators ndipo, motero, amayang'anira machitidwe osiyanasiyana amthupi, kuchokera ku chonde mpaka kupweteka. Zina mwa ntchito zodziwika bwino za ECS ndi izi:
mantha System
Kuchokera pakati pa mitsempha yapakati, kapena CNS, kukondoweza kwakukulu kwa ma CB1 receptors kudzalepheretsa kutulutsidwa kwa glutamate ndi GABA. Mu CNS, ECS imathandizira kupanga kukumbukira ndi kuphunzira, imalimbikitsa neurogenesis mu hippocampus, imayang'aniranso chisangalalo cha neuronal. ECS imakhalanso ndi gawo la momwe ubongo udzachitira kuvulala ndi kutupa. Kuchokera pamtsempha wa msana, ECS imasintha zizindikiro zowawa ndikuwonjezera analgesia yachilengedwe. Mu dongosolo lamanjenje lamkati, momwe ma CB2 receptors amawongolera, ECS imagwira ntchito makamaka mu dongosolo lamanjenje lachifundo kuwongolera ntchito zamatumbo, mkodzo, ndi zoberekera.
Kupsinjika ndi Maganizo
ECS imakhala ndi zotsatira zambiri pa kupsinjika maganizo ndi kuwongolera maganizo, monga kuyambitsa kuyankha kwa thupi ku kupsinjika maganizo ndi kusinthasintha kwa nthawi ndi kutengeka kwa nthawi yaitali, monga mantha ndi nkhawa. Dongosolo logwira ntchito lathanzi la endocannabinoid ndilofunika kwambiri momwe anthu amasinthira pakati pamlingo wokhutiritsa wa kudzutsidwa poyerekeza ndi mulingo womwe ndi wochulukira komanso wosasangalatsa. ECS imathandizanso pakupanga kukumbukira komanso makamaka makamaka momwe ubongo umasinthira kukumbukira kupsinjika kapena kuvulala. Chifukwa ECS imathandizira kutulutsidwa kwa dopamine, noradrenaline, serotonin, ndi cortisol, imathanso kukhudza kwambiri kukhudzidwa kwamalingaliro ndi machitidwe.
Chidutswa
Tract thirakiti ladzaza ndi ma CB1 ndi CB2 zolandila zomwe zimayang'anira mbali zingapo zofunika kwambiri za matenda a GI. Amaganiza kuti ECS ikhoza kukhala "cholumikizira" pofotokoza za m'matumbo omwe amalumikizana ndi mphamvu zomwe zimagwira ntchito yofunika kwambiri muumoyo wa m'mimba. ECS ndi wowongolera mphamvu ya m'matumbo, mwina poletsa chitetezo chamthupi kuti muwononge flora yabwino kwambiri, komanso kudzera pakusintha kwa ma cytokine. Anthu a EC amasinthanso yankho lachilengedwe mu thirakiti lazing'ono, lomwe lili ndi tanthauzo lofunikira kuti mupeze zovuta zosiyanasiyana. Gastric and general GI motility imawonekanso kuti imayendetsedwa pang'ono ndi ECS.
Kulakalaka ndi Metabolism
ECS, makamaka ma CB1 receptors, amathandizira pakufuna kudya, kagayidwe kazakudya, komanso kuwongolera mafuta amthupi. Kukondoweza kwa CB1 zolandilira kumadzutsa khalidwe lofunafuna chakudya, kumapangitsa kuzindikira kununkhira, kumayang'aniranso mphamvu. Zinyama zonse ndi anthu omwe ali olemera kwambiri amakhala ndi vuto la ECS lomwe lingapangitse kuti dongosololi likhale lopanda mphamvu, zomwe zimathandiza kuti pakhale kudya kwambiri komanso kuchepetsa kugwiritsa ntchito mphamvu. Miyezo yozungulira ya anandamide ndi 2-AG yasonyezedwa kuti ikukwera mu kunenepa kwambiri, zomwe zingakhale mbali imodzi chifukwa cha kuchepa kwa enzyme yowononga FAAH.
Thanzi la Chitetezo cha Mthupi ndi Mayankho Otupa
Maselo ndi ziwalo za chitetezo cha mthupi zimakhala ndi endocannabinoid receptors. Cannabinoid receptors amasonyezedwa mu thymus gland, ndulu, tonsils, ndi mafupa a mafupa, komanso pa T- ndi B-lymphocytes, macrophages, mast cell, neutrophils, ndi maselo akupha achilengedwe. ECS imawonedwa ngati dalaivala wamkulu wa chitetezo chamthupi komanso homeostasis. Ngakhale kuti si ntchito zonse za ECS kuchokera ku chitetezo cha mthupi zomwe zimamveka, ECS ikuwoneka kuti imayang'anira kupanga cytokine komanso kukhala ndi gawo loletsa kuchitapo kanthu kwa chitetezo cha mthupi. Kutupa ndi gawo lachilengedwe la chitetezo chamthupi, ndipo limagwira ntchito bwino kwambiri pakunyoza thupi, kuphatikizapo kuvulala ndi matenda; Komabe, ngati sichiyang'aniridwa bwino, imatha kudwala ndikupangitsa kuti pakhale zovuta zambiri zaumoyo, monga kupweteka kosalekeza. Poyang'anira chitetezo cha mthupi, ECS imathandiza kuti thupi likhale lopweteka kwambiri.
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Biochemistry ya Ululu:�Mapain syndrome onse amakhala ndi mbiri yotupa. Mbiri yotupa imatha kusiyana pakati pa munthu ndi munthu komanso imatha kusiyanasiyana mwa munthu m'modzi nthawi zosiyanasiyana. Chithandizo cha ma syndromes opweteka ndikumvetsetsa mbiri yotupa iyi. Ma syndromes opweteka amathandizidwa ndi mankhwala, opaleshoni kapena onse awiri. Cholinga chake ndikuletsa / kupondereza kupanga oyimira pakati otupa. Ndipo zotsatira zopambana ndi zomwe zimabweretsa kutupa kochepa komanso zowawa zochepa.
Biochemistry Of Pain
Zolinga:
Osewera ofunikira ndi ndani
Kodi ma biochemical mechanisms ndi chiyani?
Zotsatira zake ndi zotani?
Ndemanga ya Kutupa:
osewera chinsinsi
N'chifukwa Chiyani Mapewa Anga Amapweteka? Ndemanga Ya Neuroanatomical & Biochemical Basis Of Shoulder Pain
ZOKHUDZA
Ngati wodwala afunsa kuti, "N'chifukwa chiyani phewa langa likupweteka? � kukambiranako kumasintha mofulumira ku chiphunzitso cha sayansi komanso nthawi zina zopanda umboni. Kawirikawiri, dokotala amadziwa malire a maziko a sayansi a kufotokozera kwawo, kusonyeza kusakwanira kwa kumvetsetsa kwathu kwa chikhalidwe cha ululu wa mapewa. Ndemangayi imatenga njira yokhazikika yothandizira kuyankha mafunso ofunikira okhudzana ndi kupweteka kwa mapewa, ndi cholinga chopereka chidziwitso pa kafukufuku wamtsogolo ndi njira zatsopano zothandizira kupweteka kwa mapewa. Tidzafufuza ntchito za (1) zolandilira zotumphukira, (2) zowawa zotumphukira kapena �nociception�, (3) msana, (4) ubongo, (5) malo olandirira pamapewa ndi (6) ) Neural anatomy ya phewa. Timaganiziranso momwe zinthuzi zingathandizire kuti pakhale kusiyana pakati pa zochitika zachipatala, matenda ndi chithandizo cha kupweteka kwa mapewa. Mwanjira imeneyi timafuna kufotokozera mwachidule za zigawo za chigawo cha zotumphukira zowawa zotumphukira ndi njira zopangira zowawa zapakati pamapewa omwe amalumikizana kuti apange kupweteka kwachipatala.
MAU OYAMBA: MBIRI YACHIdule kwambiri YA SAYANSI YOPHUNZITSIRA ZOFUNIKA KWA MATONGO.
Chikhalidwe cha ululu, kawirikawiri, chakhala chotsutsana kwambiri m'zaka zana zapitazi. M'zaka za m'ma 17 Descartes� theory1 inanena kuti kukula kwa ululu kunali kogwirizana mwachindunji ndi kuchuluka kwa kuvulala kwa minofu yogwirizana ndi ululu umenewo unakonzedwa mu njira imodzi yosiyana. Malingaliro ambiri akale adadalira filosofi yotchedwa "dualist" Descartian filosofi, powona ululu monga chotsatira cha kukondoweza kwa "chapadera" cholandirira ululu mu ubongo. M'zaka za m'ma 20 nkhondo yasayansi pakati pa ziphunzitso ziwiri zotsutsana idachitika, zomwe ndi chiphunzitso chapadera ndi chiphunzitso cha pateni. The Descartian �specificity theory� inawona kupweteka ngati njira yosiyana ya kulowetsa kwa zomverera ndi zida zake, pamene �chiphunzitso chachitsanzo� ankaona kuti ululu umabwera chifukwa chokondoweza kwambiri kwa zolandilira zomwe sizinali zenizeni.2 Mu 1965, Wall ndi Melzack's 3 chiphunzitso cha chipata cha ululu chinapereka umboni wa chitsanzo chomwe malingaliro opweteka anasinthidwa ndi malingaliro onse okhudzidwa ndi dongosolo lapakati la mitsempha. Kupita patsogolo kwina kwakukulu mu chiphunzitso cha ululu panthawi yomweyi kunawona kupezeka kwa njira yeniyeni ya machitidwe a opioid.
Ndiye izi zikugwirizana bwanji ndi kupweteka kwa phewa?�Kupweteka kwa mapewa ndi vuto lodziwika bwino lachipatala, komanso kumvetsetsa kwamphamvu kwa momwe ululu umapangidwira ndi thupi ndikofunikira kuti muzindikire ndikuchiza ululu wa wodwala. Kupita patsogolo kwa chidziwitso chathu cha kupweteka kwapweteka kumalonjeza kufotokoza kusagwirizana pakati pa matenda ndi malingaliro a ululu, kungatithandizenso kufotokoza chifukwa chake odwala ena amalephera kuyankha mankhwala ena.
ZINTHU ZOTHANDIZA ZOTHANDIZA ZA UWAZI
Peripheral sensory receptors: mechanoreceptor ndi �nociceptor�
Pali mitundu yambiri ya zotumphukira sensory zolandilira zomwe zimapezeka mu musculoskeletal system. 5 Akhoza kugawidwa malinga ndi ntchito yawo (monga mechanoreceptors, thermoreceptors kapena nociceptors) kapena morphology (malekezero a mitsempha yaulere kapena mitundu yosiyanasiyana ya ma receptor encapsulated) . kukhalapo kwa zizindikiro za mankhwala. Pali kuphatikizika kwakukulu pakati pamagulu osiyanasiyana ogwira ntchito a ma receptor, mwachitsanzo
Peripheral Pain Processing: �Nociception�
Kuvulala kwa minofu kumaphatikizapo oyimira osiyanasiyana otupa omwe amatulutsidwa ndi maselo owonongeka kuphatikizapo bradykinin, histamine, 5-hydroxytryptamine, ATP, nitric oxide ndi ma ions ena (K + ndi H +). Kutsegula kwa njira ya arachidonic acid kumabweretsa kupanga prostaglandins, thromboxanes ndi leukotrienes. Ma Cytokines, kuphatikizapo interleukins ndi tumor necrosis factor ?, ndi neurotrophins, monga mitsempha ya kukula kwa mitsempha (NGF), amatulutsidwanso ndipo amakhudzidwa kwambiri ndikuthandizira kutupa.15 Zinthu zina monga excitatory amino acid (glutamate) ndi opioids ( endothelin-1) adakhudzidwanso ndi kuyankha kotupa kwambiri.16 17 Ena mwa othandizirawa amatha kuyambitsa mwachindunji ma nociceptors, pamene ena amabweretsa kulembedwa kwa maselo ena omwe amamasula othandizira ena. a nociceptive neurons ku zomwe amalowetsamo komanso / kapena kulembera mayankho kuzinthu zomwe zimakhudzidwa ndizomwe zimatchedwa "peripheral sensitization" .
NGF ndi transient receptor angathe cation channel subfamily V membala wa 1 (TRPV1) receptor ali ndi chiyanjano cha symbiotic pankhani ya kutupa ndi kulimbikitsana kwa nociceptor. Ma cytokines opangidwa mu minofu yowotcha amachititsa kuti NGF ichuluke.19 NGF imathandizira kutulutsidwa kwa histamine ndi serotonin (5-HT3) ndi maselo a mast, komanso imalimbikitsa ma nociceptors, mwina kusintha zinthu za A? ulusi kotero kuti gawo lalikulu limakhala losazindikira. Cholandira cha TRPV1 chilipo m'magulu ochepa a ma fiber oyambira ndipo amayendetsedwa ndi capsaicin, kutentha ndi ma protoni. Cholandilira cha TRPV1 chimapangidwa mu cell body ya afferent fiber, ndipo imatumizidwa kumadera onse apakati komanso apakati, komwe kumathandizira kukhudzidwa kwa ma nociceptive afferents. Kutupa kumabweretsa NGF kupanga zozungulira zomwe zimamangiriza ku tyrosine kinase receptor mtundu wa 1 receptor pa nociceptor terminals, NGF imatengedwa kupita ku selo cell komwe imatsogolera ku malamulo a TRPV1 kulembera ndipo chifukwa chake kuwonjezeka kwa nociceptor sensitivity.19 20 NGF ndi oyimira ena otupa amathandizanso TRPV1 kudzera m'njira zosiyanasiyana za amithenga achiwiri. Ma receptors ena ambiri kuphatikiza cholinergic receptors, ?-aminobutyric acid (GABA) receptors ndi somatostatin receptors amaganiziridwanso kuti akukhudzidwa ndi zotumphukira za nociceptor sensitivity.
Chiwerengero chachikulu cha oyimira pakati otupa chakhala chikukhudzidwa makamaka ndi ululu wa mapewa ndi matenda a rotator cuff.21�25 Ngakhale kuti oyimira pakati pamankhwala ena amayendetsa mwachindunji ma nociceptors, ambiri amayambitsa kusintha kwa neuron yodziwikiratu m'malo moiyambitsa mwachindunji. Zosinthazi zitha kukhala zotengera kumasulira koyambirira kapena kuchedwa kutengera mawu. Zitsanzo zakale ndikusintha kwa cholandilira cha TRPV1 kapena njira za ion za voltage-gated chifukwa cha phosphorylation ya mapuloteni omangidwa ndi membrane. Zitsanzo zotsirizirazi zikuphatikizapo NGF-induced kuwonjezeka kwa TRV1 kupanga njira ndi calcium-induced activation of intracellular transcription factor.
Ma Molecular Mechanism of Nociception
Kumva kupweteka kumatichenjeza za kuvulala kwenikweni kapena kumene kukubwera ndipo kumayambitsa mayankho oyenera otetezera. Tsoka ilo, ululu nthawi zambiri umaposa phindu lake ngati chenjezo ndipo m'malo mwake umakhala wokhazikika komanso wofowoka. Kusintha kumeneku kupita ku gawo losatha kumaphatikizapo kusintha kwa msana ndi ubongo, koma palinso kusintha kodabwitsa kumene mauthenga opweteka amayambika � pa mlingo wa neuron yaikulu ya sensory. Kuyesera kudziwa momwe ma neuroniwa amazindikirira zopangitsa zopweteka zamtundu wa kutentha, makina kapena mankhwala awonetsa njira zatsopano zowonetsera ndipo zatibweretsa ife pafupi kuti timvetsetse zochitika za maselo zomwe zimathandizira kusintha kuchokera ku ululu wopweteka mpaka kupweteka kosalekeza.
The Neurochemistry Of Nociceptors
Glutamate ndiye neurotransmitter yochititsa chidwi kwambiri m'ma nociceptors onse. Maphunziro a histochemical a DRG achikulire, komabe, amawulula magulu awiri otakata a C fiber osatulutsidwa.
Ma Transducers Opangira Ma Chemical Kuti Apangitse Kupweteka Kwambiri
Monga tafotokozera pamwambapa, kuvulala kumapangitsa kuti ululu wathu ukhale wopweteka powonjezera mphamvu ya nociceptors kuzinthu zonse zotentha komanso zamakina. Chodabwitsa ichi chimapangitsa, mwa zina, kupanga ndi kumasulidwa kwa oyimira pakati pa mankhwala kuchokera kumalo oyambirira a sensory komanso kuchokera ku maselo omwe si a neural (mwachitsanzo, fibroblasts, mast cell, neutrophils ndi mapulateleti) mu chilengedwe36 (mkuyu 3). Zigawo zina za supu yotupa (mwachitsanzo, ma protoni, ATP, serotonin kapena lipids) zingasinthe chisangalalo cha neuronal mwachindunji mwa kuyanjana ndi njira za ion pamtunda wa nociceptor, pamene zina (mwachitsanzo, bradykinin ndi NGF) zimamangiriza ku zolandilira za metabotropic ndi kuyanjanitsa zotsatira zawo kudzera mu ma cascades a messenger11. Kupita patsogolo kwakukulu kwachitika pakumvetsetsa maziko a biochemistry a njira zosinthira ngati izi.
Ma Protoni a Extracellular & Tissue Acidosis
Minofu acidosis ya m'deralo ndi chizindikiro chodziwikiratu kuyankha kuvulala, ndipo kuchuluka kwa ululu kapena kusapeza bwino kumayenderana ndi kukula kwa acidification37. Kugwiritsa ntchito asidi (pH 5) pakhungu kumatulutsa kutulutsa kosalekeza mu gawo limodzi mwa magawo atatu kapena kuposerapo a polymodal nociceptors omwe amasunga gawo lolandila 20.
Ma Cellular & Molecular Mechanism of Pain
Kudalirika
Dongosolo la manjenje limazindikira ndikutanthauzira mitundu yambiri yamafuta ndi makina amakasitomala komanso zowononga zachilengedwe komanso zachilengedwe. Zikafika povuta kwambiri, zochititsa chidwizi zimatulutsa ululu wowawa kwambiri, komanso pakuvulala kosalekeza, mbali zonse zam'mbali ndi zapakati zamanjenje zam'njira yopatsirana zowawa zimawonetsa pulasitiki, kukulitsa zizindikiro zowawa ndikutulutsa hypersensitivity. Pamene pulasitiki imathandizira zodzitetezera, zingakhale zopindulitsa, koma pamene kusintha kukupitirira, vuto lopweteka kwambiri likhoza kuchitika. Maphunziro a chibadwa, electrophysiological, ndi pharmacological akufotokoza njira za maselo zomwe zimayambitsa kuzindikira, kulembera, ndi kusinthasintha kwa zinthu zoopsa zomwe zimabweretsa ululu.
Glutamate/NMDA receptor-mediated sensitization.�Kutsatira kukondoweza kwambiri kapena kuvulala kosalekeza, kutsegulidwa kwa C ndi A? nociceptors amatulutsa mitundu yosiyanasiyana ya ma neurotransmitters kuphatikizapo dlutamate, mankhwala P, calcitonin-gene peptide yokhudzana ndi jini (CGRP), ndi ATP, pamtundu wa neurons mu lamina I wa nyanga yapamwamba (yofiira). Zotsatira zake, nthawi zambiri amakhala chete a NMDA glutamate receptors omwe amakhala mu postsynaptic neuron amatha kuwonetsa, kuwonjezera calcium m'kati mwa cell, ndikuyambitsa njira zambiri zolumikizirana ndi calcium ndi amithenga achiwiri kuphatikiza mitogen-activated protein kinase (MAPK), protein kinase C (PKC) , protein kinase A (PKA) ndi Src. Kuchulukira kwa zochitika izi kukulitsa chisangalalo cha ma neuron otulutsa ndikuwongolera kutumiza kwa mauthenga opweteka ku ubongo.
Kuletsa.�Munthawi yanthawi zonse, ma inhibitory interneurons (buluu) amamasula GABA ndi/kapena glycine (Gly) mosalekeza kuti achepetse chisangalalo cha lamina I linanena bungwe la neurons ndikuwongolera kufala kwa ululu (toni yoletsa). Komabe, pakuvulala, cholepheretsa ichi chikhoza kutayika, zomwe zimayambitsa hyperalgesia. Kuphatikiza apo, disinhibition imatha kupangitsa kuti non-nociceptive myelinated A? ma afferents oyambilira kuti agwirizane ndi zozungulira zopatsirana zowawa zomwe nthawi zambiri zoyambitsa zopanda vuto tsopano zikuwoneka ngati zowawa. Izi zimachitika, mwa zina, kudzera mu kuletsa kwa PKC yosangalatsa? kuwonetsa ma interneurons mu lamina II yamkati.
Kuyambitsa kwa Microglial.�Kuvulala kwa minyewa yam'mitsempha kumalimbikitsa kutulutsidwa kwa ATP ndi chemokine fractalkine zomwe zimathandizira ma cell a microglial. Makamaka, kutsegula kwa purinergic, CX3CR1, ndi Toll-like receptors pa microglia (purple) kumabweretsa kutulutsidwa kwa ubongo-derived neurotrophic factor (BDNF), yomwe kupyolera mu kutsegula kwa TrkB zolandilira zomwe zimawonetsedwa ndi lamina I output neurons, zimalimbikitsa kuwonjezereka komanso Kupweteka kowonjezereka poyankha kukondoweza koyipa komanso kosavulaza (ndiko, hyperalgesia ndi allodynia). Activated microglia imatulutsanso ma cytokines ambiri, monga tumor necrosis factor? (TNF?), interleukin-1? ndi 6 (IL-1?, IL-6), ndi zinthu zina zomwe zimapangitsa kuti pakhale chidziwitso chapakati.
The Chemical Milieu Of Inflammation
Kukhudzidwa kwapang'onopang'ono kumabwera chifukwa cha kusintha komwe kumayenderana ndi kutupa komwe kumapangidwa ndi mitsempha ya mitsempha (McMahon et al., 2008). Choncho, kuwonongeka kwa minofu nthawi zambiri kumatsagana ndi kudzikundikira kwa zinthu zomwe zimatulutsidwa kuchokera ku nociceptors kapena maselo omwe sali a neural omwe amakhala mkati kapena kulowa m'dera lovulala (kuphatikizapo mast cells, basophils, platelets, macrophages, neutrophils, endothelial cell, keratinocytes, ndi mast cell, basophils, platelets, macrophages, neutrophils, endothelial cell, keratinocytes, ndi fibroblasts). Zonse pamodzi. Zinthu izi, zomwe zimatchedwa "nsopu yotupa", zimayimira mamolekyu ambiri ozindikiritsa, kuphatikiza ma neurotransmitters, peptides (chinthu P, CGRP, bradykinin), eicosinoids ndi lipids ogwirizana (prostaglandins, thromboxanes, leukotrienes, endocannabinoids), neurotokines, , ndi chemokines, komanso ma protoni a extracellular ndi ma protoni. Chochititsa chidwi n'chakuti, ma nociceptors amasonyeza chimodzi kapena zingapo zolandirira ma cell omwe amatha kuzindikira ndi kuyankha pazigawo zonse za anti-inflammatory kapena pro-algesic (Chithunzi 4). Kuyanjana kotereku kumawonjezera chisangalalo cha minyewa ya mitsempha, potero kumakulitsa chidwi chake pakutentha kapena kukhudza.
Mosakayikira njira yodziwika bwino yochepetsera ululu wopweteka imaphatikizapo kuletsa kaphatikizidwe kapena kudzikundikira zigawo za supu yotupa. Izi zimasonyezedwa bwino ndi mankhwala osagwiritsa ntchito steroidal anti-inflammatory, monga aspirin kapena ibuprofen, omwe amachepetsa ululu wopweteka komanso hyperalgesia mwa kuletsa cyclooxygenases (Cox-1 ndi Cox-2) yomwe imakhudzidwa ndi prostaglandin synthesis. Njira yachiwiri ndiyo kuletsa zochita za othandizira otupa pa nociceptor. Apa, tikuwonetsa zitsanzo zomwe zimapereka chidziwitso chatsopano cha njira zama cell zolimbikitsa zotumphukira, kapena zomwe zimapanga maziko a njira zochiritsira zatsopano zochizira ululu wotupa.
NGF mwina imadziwika bwino chifukwa cha udindo wake monga neurotrophic factor yomwe ikufunika kuti pakhale moyo ndi chitukuko cha ma neuroni okhudzidwa panthawi ya embryogenesis, koma mwa munthu wamkulu, NGF imapangidwanso poyambitsa kuvulala kwa minofu ndipo imapanga chigawo chofunikira cha supu yotupa (Ritner et. ndi., 2009). Pakati pa zolinga zake zambiri zama cell, NGF imachita mwachindunji pa peptidergic C fiber nociceptors, yomwe imasonyeza kuyanjana kwakukulu kwa NGF receptor tyrosine kinase, TrkA, komanso low affinity neurotrophin receptor, p75 (Chao, 2003; Snider ndi McMahon, 1998). NGF imapanga kwambiri hypersensitivity kwa kutentha ndi zokopa zamakina kudzera munjira ziwiri zosiyana zanthawi. Poyamba, kuyanjana kwa NGF-TrkA kumayambitsa njira zowonetsera pansi, kuphatikizapo phospholipase C (PLC), protein kinase (MAPK) ya mitogen-activated, ndi phosphoinositide 3-kinase (PI3K). Izi zimabweretsa mphamvu yogwira ntchito ya mapuloteni omwe amawunikira pamtundu wa nociceptor terminal, makamaka TRPV1, zomwe zimapangitsa kuti pakhale kusintha kofulumira kwa kutentha kwa ma cell ndi khalidwe (Chuang et al., 2001).
Mosasamala kanthu za njira zawo zothandizira-nociceptive, kusokoneza zizindikiro za neurotrophin kapena cytokine zakhala njira yaikulu yothetsera matenda otupa kapena kupweteka. Njira yaikulu ikuphatikizapo kutsekereza NGF kapena TNF-? kuchitapo kanthu ndi anti-antibody. Pankhani ya TNF-?, izi zakhala zogwira mtima kwambiri pochiza matenda ambiri a autoimmune, kuphatikizapo nyamakazi ya nyamakazi, zomwe zimapangitsa kuchepetsa kwambiri kuwonongeka kwa minofu ndi kutsagana ndi hyperalgesia (Atzeni et al., 2005). Chifukwa chakuti zochita zazikulu za NGF pa nociceptor wamkulu zimachitika poyambitsa kutupa, ubwino wa njirayi ndikuti hyperalgesia idzachepa popanda kukhudza. yachibadwa ululu kuzindikira. Zowonadi, ma antibodies odana ndi NGF pakadali pano ali m'mayesero azachipatala kuti athe kuchiza ma syndromes opweteka (Hefti et al., 2006).
Glutamate/NMDA Receptor-Mediated Sensitization
Kupweteka koopsa kumasonyezedwa ndi kutulutsidwa kwa glutamate kuchokera kumadera apakati a nociceptors, kutulutsa mafunde a post-synaptic (EPSCs) mu dongosolo lachiwiri la dorsal horn neurons. Izi zimachitika makamaka kudzera mu activation ya postsynaptic AMPA ndi kainate subtypes ya ionotropic glutamate receptors. Chidule cha sub-threshold EPSCs mu postsynaptic neuron pamapeto pake chidzachititsa kuti pakhale kuwombera ndi kufalitsa uthenga wowawa ku ma neuron apamwamba.
Kafukufuku wina akuwonetsa kuti kusintha kwa neuron ya projection, komweko, kumathandizira kuletsa. Mwachitsanzo, kuvulala kwa mitsempha ya m'mitsempha kwambiri kumayang'anira K + - Cl-co-transporter KCC2, yomwe ndi yofunikira kuti mukhale ndi K + ndi Cl-gradients wamba kudutsa plasma membrane (Coull et al., 2003). Kuchepetsa KCC2, yomwe imasonyezedwa mu lamina I projection neurons, kumapangitsa kusintha kwa Cl- gradient, kotero kuti kutsegula kwa GABA-A receptors kumachepetsa, m'malo mwa hyperpolarize lamina I projection neurons. Izi zitha kukulitsa chisangalalo ndikuwonjezera kufalikira kwa ululu. Zowonadi, blockade ya pharmacological kapena siRNA-mediated downregulation ya KCC2 mu rat induces mechanical allodynia.
Gawani Ebook
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Chifukwa chiyani phewa langa likupweteka? Ndemanga ya neuroanatomical ndi biochemical maziko a ululu wa mapewa
Benjamin John Floyd Dean, Stephen Edward Gwilym, Andrew Jonathan Carr
Njira Zowawa za Ma cell ndi Mamolekyulu
Allan I. Basbaum1, Diana M. Bautista2, Gre?gory Scherrer1, ndi David Julius3
1Department of Anatomy, University of California, San Francisco 94158
2Department of Molecular and Cell Biology, University of California, Berkeley CA 94720 3Department of Physiology, University of California, San Francisco 94158
Njira za mamolekyu a nociception
David Julius* & Allan I. Basbaum�
*Department of Cellular and Molecular Pharmacology, and �Departments of Anatomy and Physiology and WM Keck Foundation Center for Integrative Neuroscience, University of California San Francisco, San Francisco, California 94143, USA (imelo: julius@socrates.ucsf.edu)
Kutupa kwa Neurogenic, kapena NI, ndi ndondomeko ya thupi yomwe oyimira pakati amatulutsidwa mwachindunji kuchokera ku mitsempha ya cutaneous kuti ayambe kuyankhidwa kotupa. Izi zimapangitsa kuti pakhale zochitika zotupa za m'deralo kuphatikizapo, erythema, kutupa, kuwonjezeka kwa kutentha, kukoma mtima, ndi ululu. Fine unmyelinated afferent somatic C-fibers, omwe amayankha kutsika kwamphamvu kwamakina ndi kusonkhezera kwamankhwala, makamaka ndi omwe amachititsa kutulutsa oyimira pakati otupawa.
Ikalimbikitsidwa, njira za mitsempha iyi m'mitsempha ya cutaneous imatulutsa ma neuropeptides amphamvu, kapena chinthu P ndi calcitonin peptide yokhudzana ndi jini (CGRP), mofulumira kulowa mu microenvironment, zomwe zimayambitsa mayankho ambiri otupa. Pali kusiyana kwakukulu mu kutupa kwa immunogenic, ndiko kuyankha koyamba koteteza ndi kubwezeretsa komwe kumapangidwa ndi chitetezo chamthupi pamene tizilombo toyambitsa matenda talowa m'thupi, pomwe kutupa kwa neurogenic kumaphatikizapo kulumikizana kwachindunji pakati pa dongosolo lamanjenje ndi mayankho otupa. Ngakhale kutupa kwa neurogenic ndi kutupa kwa immunological kumatha kukhalapo nthawi imodzi, ziwirizi sizidziwika bwino. Cholinga cha nkhani yomwe ili pansipa ndikukambilana za momwe kutupa kwa neurogenic ndi gawo la mitsempha yozungulira pachitetezo cha chitetezo ndi immunopathology.
Kutupa kwa Neurogenic � Udindo wa Peripheral Nervous System mu Host Defense ndi Immunopathology
Kudalirika
Zotumphukira zamanjenje ndi chitetezo chamthupi zimaganiziridwa kuti zimagwira ntchito zosiyanasiyana. Mzerewu, komabe, ukuchulukirachulukira ndi zidziwitso zatsopano za kutupa kwa neurogenic. Nociceptor neurons ali ndi njira zambiri zomwe zimazindikiritsa maselo oopsa ngati maselo a chitetezo cha mthupi komanso poyankha zoopsa, dongosolo la mitsempha la mitsempha limalankhulana mwachindunji ndi chitetezo cha mthupi, kupanga njira yotetezera chitetezo. The wandiweyani innervation network ya zomverera ndi autonomic ulusi mu zotumphukira zimakhala ndi liwiro la neural transduction amalola mofulumira m'deralo ndi zokhudza zonse neurogenic modulation wa chitetezo chokwanira. Ma peripheral neurons amawonekanso kuti amathandizira kwambiri pakuwonongeka kwa chitetezo chamthupi m'matenda a autoimmune ndi matupi awo sagwirizana. Chifukwa chake, kumvetsetsa kuyanjana kwapang'onopang'ono kwa ma neurons okhala ndi ma cell a chitetezo chamthupi kumatha kupititsa patsogolo njira zochiritsira zoonjezera chitetezo cha omwe ali nawo komanso kupondereza immunopathology.
Introduction
Zaka XNUMX zapitazo, Celsus adatanthauzira kutupa kukhala ndi zizindikiro zinayi zazikuluzikulu: Dolor (kuwawa), Calor (kutentha), Rubor (redness), ndi chotupa (kutupa), zomwe zikuwonetsa kuti kuyambitsa kwa dongosolo lamanjenje kumadziwika kuti ndi gawo lofunikira pakuchita opaleshoni. kutupa. Komabe, kupweteka kumaganiziridwa makamaka kuyambira nthawi imeneyo, kokha ngati chizindikiro, osati chotenga nawo mbali mumbadwo wa kutupa. M'malingaliro awa, tikuwonetsa kuti zotumphukira zamanjenje zimagwira ntchito yolunjika komanso yogwira ntchito pakuwongolera chitetezo chamthupi komanso chosinthika, kotero kuti chitetezo chamthupi ndi manjenje chikhoza kukhala ndi ntchito yodzitchinjiriza yodzitchinjiriza muchitetezo chachitetezo komanso kuyankha kuvulala kwa minofu, zovuta. kuyanjana komwe kungayambitsenso kudwala kwa matupi awo sagwirizana ndi autoimmune matenda.
Kupulumuka kwa zamoyo kumadalira kwambiri mphamvu yodzitchinjiriza kuti isavulazidwe ndi kuwonongeka kwa minofu ndi matenda. Chitetezo cha Host chimaphatikizapo machitidwe opewera kuti achotse kukhudzana ndi malo owopsa (owopsa) (ntchito ya neural), komanso kusalowerera ndale kwa tizilombo toyambitsa matenda (chitetezo cha chitetezo cha mthupi). Mwachizoloŵezi, ntchito ya chitetezo cha m'thupi polimbana ndi tizilombo toyambitsa matenda ndi kukonzanso kuvulala kwa minofu yakhala ikuonedwa kuti ndi yosiyana kwambiri ndi ya mitsempha ya mitsempha, yomwe imatulutsa zizindikiro zowononga zachilengedwe ndi zamkati mu ntchito yamagetsi kuti ipange zomverera komanso zowonongeka (mkuyu 1). Tikuganiza kuti machitidwe awiriwa alidi zigawo za chitetezo chogwirizana. Dongosolo lamanjenje la somatosensory limayikidwa bwino kuti lizindikire zoopsa. Choyamba, minyewa yonse yomwe imakhudzidwa kwambiri ndi chilengedwe chakunja, monga epithelial pamwamba pa khungu, mapapo, mkodzo ndi m'mimba, imakhala yosasunthika kwambiri ndi ma nociceptors, omwe amachititsa ululu wopweteka kwambiri. Kachiwiri, kutulutsa zinthu zoyipa zakunja kumakhala pafupifupi nthawi yomweyo, mwachangu kwambiri kuposa kulimbikitsa chitetezo cham'thupi, chifukwa chake akhoza kukhala "woyankha woyamba" poteteza wolandila.
Chithunzi 1: Zoyambitsa zoyipa, njira zozindikiritsa tizilombo tating'onoting'ono komanso zotupa zimayambitsa kuyambitsa kwa dongosolo lamanjenje. Ma sensory neurons ali ndi njira zingapo zodziwira kukhalapo kwa zinthu zoyipa / zovulaza. 1) Zolandilira zowopsa, kuphatikiza njira za TRP, mayendedwe a P2X, ndi zolandilira zomwe zimakhudzidwa ndi mamolekyulu (DAMP) amazindikira zidziwitso zakunja kuchokera ku chilengedwe (monga kutentha, acidity, mankhwala) kapena zidziwitso zowopsa zomwe zimatulutsidwa panthawi yovulala / kuvulala (mwachitsanzo ATP, uric acid, hydroxynonenals). 2) Pathogen recognition receptors (PRRs) monga ma Toll-like receptors (TLRs) ndi Nod-like receptors (NLRs) amazindikira Pathogen yogwirizana ndi mamolekyulu (PAMPs) okhetsedwa ndi mabakiteriya kapena ma virus omwe amalowa mthupi. 3) Ma cytokine receptors amazindikira zinthu zomwe zimatulutsidwa ndi maselo a chitetezo chamthupi (mwachitsanzo IL-1beta, TNF-alpha, NGF), yomwe imayambitsa mapu kinases ndi njira zina zowonetsera kuti ziwonjezere chisangalalo cha membrane.
Kuphatikiza pa zolowetsa m'mitsempha ya msana ndi ubongo kuchokera kumbali, zomwe zingatheke mu nociceptor neurons zimatha kupatsirana ndi antidromically panthambi mpaka kumtunda, axon reflex. Izi pamodzi ndi ma depolarizations okhazikika am'deralo amatsogolera kumasulidwa kwachangu komanso komweko kwa oyimira pakati pamitsempha kuchokera ku ma axon am'mphepete ndi ma terminals (mkuyu 2) 1. Zoyeserera zakale za Goltz (mu 1874) ndi Bayliss (mu 1901) zidawonetsa kuti mizu ya dorsal yolimbikitsa magetsi. imayambitsa vasodilation ya khungu, yomwe inatsogolera ku lingaliro la �neurogenic kutupa�, popanda kupangidwa ndi chitetezo cha mthupi (mkuyu 3).
Chithunzi 2: Zinthu za neuronal zomwe zimatulutsidwa kuchokera ku nociceptor sensory neurons zimayendetsa leukocyte chemotaxis, vascular hemodynamics ndi chitetezo cha mthupi. Pamene zoyambitsa zoopsa zimayambitsa ma sign afferent mu minyewa yamitsempha, ma antidromic axon reflexes amapangidwa omwe amapangitsa kutulutsidwa kwa ma neuropeptides pamphepete mwa minyewa. Oyimira mamolekyuwa ali ndi zochita zambiri zotupa: 1) Chemotaxis ndi kutsegula kwa neutrophils, macrophages ndi lymphocytes kumalo ovulala, ndi kuwonongeka kwa maselo a mast. 2) Kuzindikiritsa ma cell endothelial kuti awonjezere kutuluka kwa magazi, kutulutsa kwa mitsempha ndi edema. Izi zimathandizanso kuti anthu azilembanso ma leukocyte otupa. 3) Kuyamba kwa ma cell a dendritic kuti ayendetse kusiyanitsa kwa maselo a T wotsatira mu Th2 kapena Th17 subtypes.
Chithunzi 3: Nthawi yakupita patsogolo pakumvetsetsa mbali za neurogenic za kutupa kuchokera ku Celsus mpaka lero.
Kutupa kwa Neurogenic kumayendetsedwa ndi kutulutsidwa kwa neuropeptides calcitonin peptide yokhudzana ndi jini (CGRP) ndi chinthu P (SP) kuchokera ku nociceptors, zomwe zimagwira ntchito mwachindunji pa vascular endothelial ndi maselo osalala a minofu 2�5. CGRP imapanga zotsatira za vasodilation 2, 3, pamene SP imawonjezera kutsekemera kwa capillary komwe kumatsogolera ku plasma extravasation ndi edema 4, 5, zomwe zimathandizira ku rubor, calor ndi chotupa cha Celsus. Komabe, ma nociceptors amamasula ma neuropeptides ambiri owonjezera (database yapaintaneti: www.neuropeptides.nl/), kuphatikizapo Adrenomedullin, Neurokinins A ndi B, Vasoactive intestinal peptide (VIP), neuropeptide (NPY), ndi gastrin release peptide (GRP), komanso oyimira ma molekyulu ena monga glutamate, nitric oxide (NO) ndi ma cytokines monga eotaxin. 6.
Tsopano tikuyamikira kuti oyimira pakati omwe amatulutsidwa kuchokera ku ma neuron ozungulira m'mphepete mwake samangogwira ntchito pa vasculature, komanso amakopa mwachindunji ndi kuyambitsa maselo a chitetezo chamthupi (mast cell, dendritic cell), ndi ma adaptive immune cell (T lymphocytes) 7�12. M'malo ovuta kwambiri a kuwonongeka kwa minofu, timaganiza kuti kutupa kwa neurogenic kumateteza, kumathandizira kuchira kwa bala komanso chitetezo chamthupi ku tizilombo toyambitsa matenda poyambitsa ndikulemba ma cell a chitetezo. Komabe, kulumikizana kotereku kwa neuro-immune kumakhalanso ndi gawo lalikulu mu pathophysiology ya matupi awo sagwirizana ndi autoimmune matenda pokulitsa mayankho a pathological kapena maladaptive. Mu zitsanzo za nyama za nyamakazi ya nyamakazi mwachitsanzo, Levine ndi anzake asonyeza kuti kuchotsedwa kwa olowa kumabweretsa kuchepa kwakukulu mu kutupa, zomwe zimadalira mafotokozedwe a mitsempha ya zinthu P 13, 14. psoriasis, primary sensory neurons amatenga gawo lalikulu poyambitsa ndi kukulitsa kutsegulira kwa chitetezo cham'mimba komanso chosinthika 15�17.
Njira Zozindikiritsa Zowopsa Zogawana M'mitsempha ya Mitsempha ndi Njira Zam'mimba Zam'mimba
Peripheral sensory neurons amasinthidwa kuti azindikire kuopsa kwa chamoyo chifukwa cha kukhudzika kwawo kwamphamvu kwambiri yamakina, matenthedwe komanso owopsa amankhwala (mkuyu 1). Transient receptor potential (TRP) njira za ion ndizomwe zimaphunziridwa kwambiri ndi oyimira ma molekyulu a nociception, omwe amalowetsa ma cations osasankha poyambitsa ndi zovuta zosiyanasiyana. TRPV1 imayendetsedwa ndi kutentha kwakukulu, pH yochepa ndi capsaicin, chigawo cha vallinoid irritant cha tsabola tsabola 18. TRPA1 imagwirizanitsa kuzindikira kwa mankhwala okhudzidwa ndi zinthu zomwe zimawononga chilengedwe monga misozi ya misozi ndi mafakitale isothiocyanates 19, koma chofunika kwambiri, imagwiranso ntchito panthawi ya minofu. kuvulala ndi ma siginecha amkati amkati kuphatikiza 4-hydroxynonenal ndi prostaglandins 20, 21.
Chochititsa chidwi n'chakuti, ma neuroni amagawana zambiri za tizilombo toyambitsa matenda ndi zoopsa zowonongeka kwa maselo ovomerezeka monga maselo oteteza thupi, omwe amawathandiza kuti azindikire tizilombo toyambitsa matenda (mkuyu 1). Mu chitetezo chamthupi, tizilombo toyambitsa matenda timadziwikiratu ndi majeremusi otchedwa germline encoded pattern recognition receptors (PRRs), omwe amazindikira ma pathogen-associated molecular pathology (PAMPs). Ma PRR oyambirira omwe anadziwika anali mamembala a banja la toll-like receptor (TLR), omwe amamangiriza ku yisiti, zigawo za cell-wall zomwe zimachokera ku bakiteriya ndi ma virus a RNA 22. Pambuyo poyambitsa PRR, njira zowonetsera pansi zimatsegulidwa zomwe zimapangitsa kuti cytokine ipangidwe ndi kuyambitsa. a adaptive chitetezo. Kuphatikiza pa TLRs, maselo a chitetezo chamthupi amayendetsedwa panthawi yovulazidwa kwa minofu ndi zizindikiro zoopsa zomwe zimachokera ku endogenous, zomwe zimadziwikanso kuti zowonongeka zowonongeka (DAMPs) kapena alarmins 23, 24. Zizindikiro zoopsazi zikuphatikizapo HMGB1, uric acid, ndi mapuloteni a kutentha kwa kutentha omwe amatulutsidwa. ndi kufa maselo pa necrosis, activating maselo chitetezo pa sanali opatsirana yotupa mayankho.
PRRs kuphatikizapo TLRs 3, 4, 7, ndi 9 amasonyezedwa ndi nociceptor neurons, ndipo kukondoweza ndi TLR ligands kumabweretsa kulowetsedwa kwa mafunde amkati ndi kulimbikitsa ma nociceptors ku zovuta zina zowawa 25�27. Kuwonjezera apo, kutsegula kwa ma neuroni okhudzidwa ndi TLR7 ligand imiquimod kumapangitsa kuti pakhale njira yowonongeka ya 25. Zotsatirazi zimasonyeza kuti ululu wokhudzana ndi matenda ndi kuyabwa kungakhale chifukwa cha kutsegula mwachindunji kwa ma neuroni ndi zinthu zomwe zimachokera ku tizilombo toyambitsa matenda, zomwe zimachititsa kuti tizilombo toyambitsa matenda tizilombo toyambitsa matenda tizilombo toyambitsa matenda tizilombo toyambitsa matenda. yambitsani ma cell a chitetezo chamthupi kudzera m'mitsempha yotulutsa ma molekyulu a neuronal.
DAMP / alarmin yaikulu yomwe imatulutsidwa panthawi ya kuvulala kwa ma cell ndi ATP, yomwe imadziwika ndi purinergic receptors pa nociceptor neurons ndi maselo a chitetezo cha mthupi 28�30. Purinergic receptors amapangidwa ndi mabanja awiri: P2X receptors, ligand-gated cation channels, ndi P2Y receptors, G-protein coupled receptors. Mu nociceptor neurons, kuzindikira kwa ATP kumachitika kudzera mu P2X3, zomwe zimatsogolera ku mafunde othamanga kwambiri komanso kupweteka kwa 28, 30 (mkuyu 1), pamene P2Y receptors amathandiza kuti nociceptor activation ndi kulimbikitsa TRP ndi voltage-gated sodium channels. Mu macrophages, ATP yomangiriza ku P2X7 receptors imatsogolera ku hyperpolarization, ndi kutsika kwapansi kwa inflammasome, mamolekyu ovuta kwambiri omwe amafunikira m'badwo wa IL-1beta ndi IL-18 29. Choncho, ATP ndi chizindikiro changozi champhamvu chomwe chimayambitsa ma neuroni onse ozungulira komanso obadwa nawo. chitetezo chamthupi pakuvulala, ndipo umboni wina umasonyeza kuti ma neuroni amawonetsa mbali za makina a inflammasome molecular 31.
Mbali yapang'onopang'ono yazizindikiro zowopsa mu nociceptors ndi gawo la njira za TRP pakuyambitsa ma cell cell. TRPV2, homologue ya TRPV1 yoyendetsedwa ndi kutentha koopsa, imasonyezedwa pamiyeso yambiri m'maselo a chitetezo chamthupi 32. Kutulutsa kwachibadwa kwa TRPV2 kunayambitsa zolakwika mu macrophage phagocytosis ndi chilolezo cha matenda a bakiteriya 32. Mast cell amasonyezanso njira za TRPV, zomwe zingathe kugwirizanitsa mwachindunji. degranulation yawo 33. Zimatsalira kuti zitsimikizidwe ngati zizindikiro zowonongeka zowonongeka zimayambitsa maselo a chitetezo cha mthupi mofanana ndi ma nociceptors.
Njira yaikulu yolankhulirana pakati pa maselo a chitetezo cha mthupi ndi ma nociceptor neurons ndi kudzera mu cytokines. Pambuyo poyambitsa ma cytokine receptors, njira zotumizira ma siginecha zimayendetsedwa mumitsempha yama cell yomwe imatsogolera kumunsi kwa phosphorylation ya mapuloteni a membrane kuphatikiza TRP ndi ma voltage-gated channels (mkuyu 1). Zomwe zimachititsa kuti ma nociceptors zitheke kumatanthauza kuti nthawi zambiri zowonongeka zowonongeka ndi kutentha zimatha kuyambitsa ma nociceptors. Interleukin 1 beta ndi TNF-alpha ndi ma cytokine awiri ofunikira omwe amatulutsidwa ndi maselo obadwa nawo a chitetezo chamthupi panthawi yotupa. IL-1beta ndi TNF-alpha zimamveka mwachindunji ndi ma nociceptors omwe amasonyeza kuti amavomereza, amachititsa kuti p38 map kinases ayambe kuchititsa kuti membrane ikhale yosangalatsa 34�36. Nerve growth factor (NGF) ndi prostaglandin E (2) ndiwonso oyimira pakati otupa omwe amatulutsidwa kuchokera ku maselo a chitetezo chamthupi omwe amagwira ntchito mwachindunji pama peripheral sensory neurons kuti apangitse chidwi. Chofunikira cha nociceptor sensitization ndi chitetezo cha mthupi ndi kuwonjezeka kwa ma neuropeptides pazigawo zozungulira zomwe zimapangitsa kuti maselo a chitetezo cha mthupi apitirire, motero amachititsa kuti phokoso likhale labwino lomwe limayendetsa ndikuthandizira kutupa.
Sensory Nervous System Control ya Innate ndi Adaptive Immunity
Kumayambiriro koyambirira kwa kutupa, ma neuroni akumva amawonetsa ma cell a mast cell ndi ma cell a dendritic, omwe ndi maselo oteteza thupi omwe ali ofunikira poyambitsa kuyankha kwa chitetezo chamthupi (mkuyu 2). Maphunziro a anatomical awonetsa kukhazikitsidwa kwachindunji kwa ma terminals okhala ndi ma mast cell, komanso ma cell a dendritic, ndipo ma neuropeptides otulutsidwa kuchokera ku nociceptors amatha kuyambitsa degranulation kapena kupanga cytokine m'maselo awa 7, 9, 37. Kulumikizana uku kumagwira ntchito yofunika kwambiri pamayendedwe osagwirizana ndi mpweya. kutupa ndi dermatitis 10�12.
Pa gawo loyambitsa kutupa, maselo a chitetezo chamthupi amayenera kupeza njira yopita ku malo enieni ovulala. Oyimira pakati ambiri omwe amatulutsidwa kuchokera ku ma neuropeptides, ma neuropeptides, chemokines, ndi glutamate, ndi chemotactic kwa neutrophils, eosinophils, macrophages, ndi T-maselo, ndipo amathandizira endothelial adhesion yomwe imathandizira kuti chitetezo cha mthupi chitetezeke 6, 38�41 (Mkuyu 2). Kuphatikiza apo, umboni wina umasonyeza kuti ma neuroni amatha kutenga nawo mbali mu gawo lothandizira, monga ma neuropeptides iwonso amatha kukhala ndi ntchito za antimicrobial 42.
Mamolekyu ozindikiritsa opangidwa ndi Neuronally amathanso kuwongolera mtundu wa kutupa, pothandizira kusiyanitsa kapena kufotokozedwa kwamitundu yosiyanasiyana ya ma cell a chitetezo chamthupi T. Antigen imapangidwa ndi phagocytosed ndikusinthidwa ndi maselo obadwa nawo, omwe amasamukira ku lymph node yapafupi ndikupereka antigenic peptide ku maselo a T. Kutengera ndi mtundu wa ma antigen, mamolekyu opangira ma cell a chitetezo chamthupi, komanso kuphatikiza kwa ma cytokines ena, ma cell a nave T amakhwima kukhala ma subtypes ena omwe amagwira bwino ntchito yotupa kuti achotse zoyambitsa matenda. Maselo a CD4 T, kapena T wothandizira (Th) maselo, akhoza kugawidwa m'magulu anayi, Th1, Th2, Th17, ndi T regulatory cells (Treg). Maselo a Th1 amatenga nawo gawo pakuwongolera mayankho a chitetezo chamthupi ku tizilombo tating'onoting'ono tating'onoting'ono komanso matenda amtundu wa autoimmune; Th2 ndi yofunika kwambiri kuti chitetezo chitetezeke ku tizilombo toyambitsa matenda, monga helminths, ndipo ndizomwe zimayambitsa matenda otupa; Maselo a Th17 amatenga gawo lalikulu poteteza ku zovuta za tizilombo toyambitsa matenda, monga mabakiteriya a extracellular ndi bowa; Ma cell a Treg amatenga nawo gawo pakusunga kudzilekerera ndikuwongolera mayankho a chitetezo chamthupi. Kukula kwa ma cell a T kumawoneka kuti kumakhudzidwa kwambiri ndi oyimira pakati pa ma neuronal. Ma neuropeptides, monga CGRP ndi VIP, amatha kukondera ma cell a dendritic kupita ku chitetezo chamtundu wa Th2 ndikuchepetsa chitetezo chamtundu wa Th1 mwa kulimbikitsa kupanga ma cytokines ena ndikuletsa ena, komanso kuchepetsa kapena kupititsa patsogolo kusamuka kwa maselo a dendritic kupita ku ma lymph node 8. , 10, 43. Sensory neurons imathandizanso kwambiri ku ziwengo (makamaka Th2 yoyendetsedwa) kutupa 17. Kuwonjezera pa kulamulira maselo a Th1 ndi Th2, ma neuropeptides ena, monga SP ndi Hemokinin-1, akhoza kuyendetsa yankho lotupa kwambiri ku Th17 kapena Treg. 44, 45, zomwe zikutanthauza kuti ma neuroni amathanso kutenga nawo gawo pakuwongolera kusamvana kotupa. Mu ma immunopathologies monga colitis ndi psoriasis, kutsekeka kwa oyimira pakati pa neuronal monga chinthu P kumatha kutsitsa kwambiri T cell ndi kuwonongeka kwa chitetezo chamthupi 15�17, ngakhale kutsutsa mkhalapakati m'modzi kokha kungakhale ndi zotsatira zochepa pa kutupa kwa neurogenic.
Poganizira kuti mamolekyu owonetsa omwe amatulutsidwa kuchokera ku zotumphukira zamitsempha zam'mitsempha amawongolera osati mitsempha yaying'ono yamagazi, komanso chemotaxis, homing, kusasitsa, ndi kuyambitsa kwa maselo a chitetezo chamthupi, zikuwonekeratu kuti kulumikizana kwa neuro-immune ndikovuta kwambiri kuposa momwe amaganizira kale (Mkuyu. . 2). Komanso, n'zosadabwitsa kuti sizomwe zimagwirizanitsa ndi neural koma zimakhala zosakanikirana za ma molekyulu omwe amatulutsidwa kuchokera ku ma nociceptors omwe amakhudza magawo osiyanasiyana ndi mitundu ya mayankho a chitetezo cha mthupi.
Autonomic Reflex Control of Immunity
Ntchito ya cholinergic autonomic nerve system �reflex� poyang'anira chitetezo chamthupi cham'mbuyo ikuwonekeranso kwambiri 46. Vagus ndi mitsempha yayikulu ya parasympathetic yomwe imagwirizanitsa ubongo ndi ziwalo za visceral. Ntchito yolembedwa ndi Kevin Tracey ndi ena amalozera ku mayankho amphamvu oletsa kutupa mu septic shock ndi endotoxemia, oyambitsidwa ndi zochitika zina za vagal nerve zomwe zimatsogolera ku kuponderezedwa kwa macrophages 47�49. Vagus imayendetsa zotumphukira za adrenergic celiac ganglion neurons zomwe zimatsekereza ndulu, zomwe zimapangitsa kutsika kwa acetylcholine, komwe kumamangiriza ku alpha-7 nicotinic receptors pa macrophages mu ndulu ndi m'mimba. Izi zimapangitsa kuti JAK2 / STAT3 SOCS3 iwonetsere njira yowonetsera, yomwe imalepheretsa mwamphamvu kulembedwa kwa TNF-alpha 47. Gulu la adrenergic celiac ganglion limalankhulanso mwachindunji ndi kachigawo kakang'ono ka acetylcholine kamene kamapanga kukumbukira T maselo, omwe amalepheretsa kutupa kwa macrophages 48.
Invariant natural Killer T cell (iNKT) ndi gulu lapadera la ma T cell omwe amazindikira ma microbial lipids mu nkhani ya CD1d m'malo mwa ma antigen a peptide. Ma cell a NKT ndi gawo lalikulu la ma lymphocyte omwe amakhudzidwa polimbana ndi matenda opatsirana komanso kuwongolera chitetezo chamthupi. Maselo a NKT amakhala ndi magalimoto makamaka kudzera mu mitsempha ndi sinusoids ya ndulu ndi chiwindi. Mitsempha yachifundo ya beta-adrenergic m'chiwindi imawonetsa mwachindunji kusintha ntchito ya NKT cell 50. Pa chitsanzo cha mbewa (MCAO), mwachitsanzo, chiwindi cha NKT kusuntha kwa selo kunkaponderezedwa, komwe kunasinthidwa ndi kukhumudwa kwachifundo kapena beta-adrenergic antagonists. Kuphatikiza apo, ntchito ya immunosuppressive iyi ya noradrenergic neurons pama cell a NKT idapangitsa kuti matenda achuluke komanso kuvulala kwamapapo. Chifukwa chake, ma signature ochokera ku autonomic neurons amatha kuyanjanitsa mphamvu ya immunosuppression.
Kuzindikira kwa Dr. Alex Jimenez
Kutupa kwa Neurogenic ndi kuyankha kotupa komwe kumapangidwa ndi dongosolo lamanjenje. Zimakhulupirira kuti zimagwira ntchito yofunika kwambiri pa matenda osiyanasiyana a zaumoyo, kuphatikizapo, migraine, psoriasis, mphumu, fibromyalgia, eczema, rosacea, dystonia ndi multiple chemical sensitivity. Ngakhale kutupa kwa neurogenic komwe kumayenderana ndi zotumphukira zamanjenje kwafufuzidwa mozama, lingaliro la kutupa kwa neurogenic mkati mwa dongosolo lapakati la mitsempha likufunikabe kufufuza kwina. Malinga ndi kafukufuku wambiri wofufuza, komabe, kuperewera kwa magnesium kumakhulupirira kuti ndiko chifukwa chachikulu cha kutupa kwa neurogenic. Nkhani yotsatirayi ikuwonetsa mwachidule njira za kutupa kwa neurogenic mu dongosolo la mitsempha, zomwe zingathandize akatswiri a zaumoyo kudziwa njira yabwino yothandizira kuti asamalire matenda osiyanasiyana okhudzana ndi dongosolo lamanjenje.
Mawuwo
Kodi ndi maudindo otani enieni a somatosensory ndi autonomic mantha system pakuwongolera kutupa ndi chitetezo chamthupi (mkuyu 4)? Kutsegula kwa ma nociceptors kumabweretsa ma axon reflexes am'deralo, omwe m'deralo amatenga ndi kuyambitsa maselo a chitetezo chamthupi ndipo motero, makamaka pro-yotupa komanso otsekeredwa m'malo. Mosiyana ndi izi, kukondoweza kwa autonomic kumabweretsa chitetezo chamthupi mwa kusokoneza ma cell a chitetezo m'chiwindi ndi ndulu. Njira zolumikizirana zolumikizirana zomwe zimatsogolera pakuyambitsa kwa immunosuppressive vagal cholinergic reflex dera sizimamveka bwino. Komabe, 80-90% ya ulusi wa vagal ndi woyambira wolumikizana ndi ulusi, chifukwa chake mazizindikiro ochokera ku viscera, ambiri omwe amatha kuyendetsedwa ndi ma cell a chitetezo chamthupi, angayambitse kuyambitsa kwa ma interneuron muubongo ndi kudzera mwa iwo kutulutsa mu efferent vagal ulusi 46.
Chithunzi 4: Zomverera komanso zodziyimira pawokha zamanjenje zimayendetsa mayankho am'deralo ndi amthupi motsatana. Nociceptors innervating epithelial surfaces (monga khungu ndi mapapo) amachititsa kuti anthu azitha kuyamwa, kuyambitsa maselo a mast ndi maselo a dendritic. Kutupa kwapakhungu, dermatitis ndi nyamakazi ya nyamakazi, ma nociceptor neurons amathandizira kuyendetsa kutupa. Mosiyana ndi izi, mabwalo odziyimira pawokha omwe amasunga ziwalo za visceral (mwachitsanzo ndulu ndi chiwindi) zimayang'anira chitetezo chamthupi mwa kutsekereza ma macrophage ndi NKT cell activation. Mu sitiroko ndi septic endotoxemia, ma neuron awa amatenga gawo loletsa chitetezo chamthupi.
Kawirikawiri, nthawi ya nthawi ndi chikhalidwe cha kutupa, kaya pa nthawi ya matenda, ziwengo, kapena auto-immune pathologies, zimatanthauzidwa ndi magulu a chitetezo cha mthupi omwe akukhudzidwa. Zidzakhala zofunikira kudziwa kuti ndi mitundu iti ya maselo a chitetezo cha mthupi omwe amayendetsedwa ndi zizindikiro zomveka komanso zodziimira. Kuwunika mwadongosolo zomwe oyimira pakati angatulutsidwe kuchokera ku ma nociceptors ndi autonomic neurons ndi mafotokozedwe a zolandilira izi ndi ma cell osiyanasiyana obadwa nawo komanso osinthika omwe angathandize kuthana ndi funsoli.
Panthawi ya chisinthiko, njira zodziwira zoopsa zofananira za maselo zakhala zikuthandizira chitetezo cham'mimba komanso nociception ngakhale maselo ali ndi mibadwo yosiyana kwambiri. Ngakhale kuti ma PRRs ndi ma ion owopsa a ligand-gated ion amawerengedwa mosiyana ndi akatswiri a immunologists ndi neurobiologists, mzere pakati pa magawo awiriwa ukuchulukirachulukira. Pakuwonongeka kwa minofu ndi matenda oyambitsa matenda, kutulutsidwa kwa zidziwitso zowopsa kumatha kupangitsa kuti ma neuroni am'mphepete ndi ma cell a chitetezo azitha kulumikizana movutikira, komanso chitetezo chophatikizika. Maonekedwe a anatomical a nociceptors pa mawonekedwe ndi chilengedwe, kuthamanga kwa neural transduction ndi kuthekera kwawo kumasula ma cocktails amphamvu a oyimira chitetezo chamthupi amalola dongosolo la mitsempha la m'mphepete mwa nyanja kuti lizitha kuyendetsa bwino mphamvu ya chitetezo cha m'thupi ndikugwirizanitsa kutsika kwa chitetezo cha mthupi. Mosiyana ndi zimenezi, ma nociceptors amakhudzidwa kwambiri ndi otetezera chitetezo cha mthupi, omwe amachititsa ndi kulimbikitsa ma neuroni. Chifukwa chake, kutupa kwa Neurogenic ndi chitetezo chamthupi sizinthu zodziyimira pawokha koma zimagwira ntchito ngati zida zochenjeza koyambirira. Komabe, zotumphukira zamitsempha zimathandizanso kwambiri pathophysiology, ndipo mwina etiology, ya matenda ambiri a chitetezo chamthupi monga mphumu, psoriasis, kapena colitis chifukwa mphamvu yake yoyambitsa chitetezo chamthupi imatha kukulitsa kutupa kwa pathological 15�17. Chithandizo cha matenda a chitetezo chamthupi chingafunikire kuphatikiza, motero, kulunjika kwa ma nociceptors komanso ma cell a chitetezo chamthupi.
Pomaliza,�Kumvetsetsa gawo la kutupa kwa neurogenic pankhani ya chitetezo ndi immunopathology ndikofunikira pakuzindikira njira yoyenera yamankhwala pazinthu zosiyanasiyana zamanjenje. Poyang'ana kuyanjana kwa ma neurons ozungulira ndi maselo oteteza thupi, akatswiri azachipatala amatha kupititsa patsogolo njira zochiritsira kuti athandizire kuwonjezera chitetezo cha omwe ali nawo komanso kupondereza immunopathology. Cholinga cha nkhani yomwe ili pamwambapa ndikuthandizira odwala kumvetsetsa zachipatala cha neurophysiology ya neuropathy, pakati pazovuta zina za thanzi la mitsempha. Zambiri zomwe zatchulidwa kuchokera ku National Center for Biotechnology Information (NCBI). Kuchuluka kwa chidziwitso chathu kumangokhala kwa chiropractic komanso kuvulala kwa msana ndi mikhalidwe. Kuti mukambirane nkhaniyi, chonde muzimasuka kufunsa Dr. Jimenez kapena mutitumizireni pa�915-850-0900 .
Wosankhidwa ndi Dr. Alex Jimenez
Mitu Yowonjezera: Ululu Wobwerera
Ululu wammbuyo ndi chimodzi mwa zifukwa zofala kwambiri za olumala ndi masiku osowa kuntchito padziko lonse lapansi. Kunena zoona, kupweteka kwa msana kwanenedwa kuti ndi chifukwa chachiwiri chofala kwambiri choyendera ofesi ya dokotala, choposa kokha ndi matenda apamwamba opuma. Pafupifupi 80 peresenti ya anthu adzakhala ndi mtundu wina wa ululu wammbuyo kamodzi pa moyo wawo wonse. Msana ndi dongosolo lovuta lopangidwa ndi mafupa, mafupa, mitsempha ndi minofu, pakati pa ziwalo zina zofewa. Chifukwa cha izi, kuvulala ndi / kapena zovuta, monga herniated discs, pamapeto pake zimatha kuyambitsa zizindikiro za ululu wammbuyo. Kuvulala kwamasewera kapena ngozi zapamsewu nthawi zambiri zimakhala zomwe zimayambitsa kupweteka kwa msana, komabe, nthawi zina kuyenda kosavuta kumakhala ndi zotsatira zowawa. Mwamwayi, njira zina zochiritsira, monga chisamaliro cha chiropractic, zingathandize kuchepetsa ululu wammbuyo pogwiritsa ntchito kusintha kwa msana ndi kusintha kwamanja, potsirizira pake kumathandiza kuchepetsa ululu.
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Kudalirika
Zothandizira:
N'chifukwa Chiyani Mapewa Anga Amapweteka? Ndemanga Ya Neuroanatomical & Biochemical Basis Of Shoulder Pain
NGF ndi transient receptor angathe cation channel subfamily V membala wa 1 (TRPV1) receptor ali ndi chiyanjano cha symbiotic pankhani ya kutupa ndi kulimbikitsana kwa nociceptor. Ma cytokines opangidwa mu minofu yowotcha amachititsa kuti NGF ichuluke.19 NGF imathandizira kutulutsidwa kwa histamine ndi serotonin (5-HT3) ndi maselo a mast, komanso imalimbikitsa ma nociceptors, mwina kusintha zinthu za A? ulusi kotero kuti gawo lalikulu limakhala losazindikira. Cholandira cha TRPV1 chilipo m'magulu ochepa a ma fiber oyambira ndipo amayendetsedwa ndi capsaicin, kutentha ndi ma protoni. Cholandilira cha TRPV1 chimapangidwa mu cell body ya afferent fiber, ndipo imatumizidwa kumadera onse apakati komanso apakati, komwe kumathandizira kukhudzidwa kwa ma nociceptive afferents. Kutupa kumabweretsa NGF kupanga zozungulira zomwe zimamangiriza ku tyrosine kinase receptor mtundu wa 1 receptor pa nociceptor terminals, NGF imatengedwa kupita ku selo cell komwe imatsogolera ku malamulo a TRPV1 kulembera ndipo chifukwa chake kuwonjezeka kwa nociceptor sensitivity.19 20 NGF ndi oyimira ena otupa amathandizanso TRPV1 kudzera m'njira zosiyanasiyana za amithenga achiwiri. Ma receptors ena ambiri kuphatikiza cholinergic receptors, ?-aminobutyric acid (GABA) receptors ndi somatostatin receptors amaganiziridwanso kuti akukhudzidwa ndi zotumphukira za nociceptor sensitivity.
The Neurochemistry Of Nociceptors
Ma Cellular & Molecular Mechanism of Pain
Chithunzi 5. Kulimbikitsa Msana (Chapakati) Kulimbikitsa
