I-Biochemistry of Pain:Zonke iisyndromes zentlungu zineprofayile yokukrala. Iprofayili yokuvuvukala ingahluka ukusuka kumntu ukuya emntwini kwaye inokwahluka kumntu omnye ngamaxesha ahlukeneyo. Unyango lwee-syndromes zentlungu kukuqonda iprofayile yokuvuvukala. Iintlungu ze-syndromes zinyangwa ngokwamayeza, ngokuhlinzwa okanye zombini. Injongo kukuthintela / ukucinezela ukuveliswa kwabalamli abanokudumba. Kwaye isiphumo esiphumeleleyo sesinye esikhokelela kukudumba okuncinci kwaye kunjalo iintlungu zingaphantsi.
Contents
Ukuba isigulana sibuza ukuba "kutheni igxalaba lam libuhlungu?" Incoko iyakuthi iphethuke iye kwithiyori kwaye ngamanye amaxesha ingqibelelo engaqinisekiswanga. Rhoqo, ugqirha uyayiqonda imida yesiseko senzululwazi yenkcazo yabo, ebonisa ukungaphelelanga kokuqonda kwethu imeko yentlungu egxalabeni. Olu hlaziyo luthatha indlela emiselweyo yokunceda ukuphendula imibuzo esisiseko enxulumene nentlungu egxalabeni, ngenjongo yokubonelela ngolwazi kuphando lwexesha elizayo kunye neendlela ezintsha zokunyanga iintlungu zamagxa. Siza kuphonononga iindima ze (1) ii-peripheral receptors, (2) ukuqhutywa kwentlungu okanye i- nociception , (3) intambo yomqolo, (4) ingqondo, (5) indawo ezamkela kuyo igxalaba kunye (6) i-neural anatomy yegxalaba. Sikwathathela ingqalelo ukuba ezi zinto zinokuba negalelo njani kuguquko kwinkcazo yeklinikhi, isifo kunye nonyango lweentlungu. Ngale ndlela sijolise ekunikezeleni isishwankathelo samacandelo enkqubo yokubona iintlungu kunye neenkqubo zokulungisa iintlungu ezisezintlungwini ezinxibelelana ukuvelisa iintlungu zeklinikhi.
Uhlobo lwentlungu, ngokubanzi, ibingumba ophikisanayo kakhulu kwinkulungwane edlulileyo. Kwinkulungwane ye-17th Descartes theory1 yacebisa ukuba ubunzima beentlungu buhambelana ngqo nenqanaba lokulimala kwezicubu kunye nokuba iintlungu zalungiswa ngendlela enye eyahlukileyo. Iithiyori ezininzi zangaphambili zazixhomekeke kule nto ibizwa ngokuba yi- dualist Descartian bulumko, ibona iintlungu njengesiphumo sokuvuselelwa kwe- specific peripheral pain receptor kwingqondo. Kwinkulungwane yama-20 idabi lobunzululwazi elaliphakathi kweembono ezimbini eziphikisanayo ezalandelayo, ezizezi ithiyori ekhethekileyo kunye nethiyori yomzekelo. I-Descartian specityity theory yabona iintlungu njengendlela ethile eyahlukileyo yokufaka uluvo kunye nezixhobo zayo, ngelixa i-theory aziva ukuba iintlungu zibangelwe kukuvuseleleka okungamkelekanga kwee-receptors.2 Kwi-1965, Wall kunye neMelzack s 3 Ithiyori yesango lentlungu ibonelele ubungqina bemodeli apho iintlungu zokuqonda zalungiswa khona ngempendulo yeemvakalelo kunye nenkqubo ye-nervous system. Enye inkqubela phambili enkulu kwithiyori yentlungu ngaxeshanye yabona ukufunyanwa kwendlela ethile yezenzo ze-opioids.4 Emva koko, inkqubela phambili yamva nje ye-neuroimaging kunye neyeza lemolekyuli ikwandisile ngokubanzi ukuqonda kwethu kwentlungu.
Ke oku kunxulumana njani neentlungu zamagxa?�Intlungu yentlungu yinkinga eqhelekileyo yeklinikhi, kunye nokuqonda okunamandla kwendlela iintlungu ezenziwa ngayo ngumzimba kubalulekile ekuchongeni nasekunyangeni iintlungu zesigulana. Ukuqhubela phambili kulwazi lwethu lokulungisa iintlungu kuthembisa ukungahambelani phakathi kwesifo kunye nembono yeentlungu, zinokusinceda ukuba sichaze ukuba kutheni izigulana zisilela ukuphendula kunyango oluthile.
Zininzi iintlobo zeepheripheral sensory receptors ezikhoyo kwinkqubo yemisipha yomntu. 5 Banokuhlelwa ngokusekwe kwimisebenzi yabo (njengee-mechanoreceptors, i-thermoreceptors okanye i-nociceptors) okanye i-morphology (iziphelo zamahala ezikhululekileyo okanye iintlobo ezahlukeneyo ze-receptors) .5 Iindidi ezahlukeneyo ze-receptor emva koko zinokuxhaswa ngakumbi ngokusekwe ubukho babamakishi abathile beekhemikhali. Kukho ukugqabhuka okubalulekileyo phakathi kweeklasi ezahlukeneyo zomsebenzi we-receptor, umzekelo
Ukulimala kwezicubu kubandakanya iintlobo zabalamli abanokudumba abakhutshwa ziiseli ezonakalisiweyo kubandakanya i-bradykinin, i-histamine, i-5-hydroxytryptamine, i-ATP, i-nitric oxide kunye nee-ions ezithile (K + kunye ne-H +). Ukusebenza kwendlela ye-arachidonic acid kukhokelela kwimveliso ye-prostaglandins, i-thromboxanes kunye ne-leuko- trienes. IiCytokines, kubandakanya ii-interleukins kunye ne-tumor necrosis factor? I-endothelin-15) ikwanyanzelisiwe kwimpendulo ebukhali yokuvuvukala.1 16 Ezinye zezi arhente zinokusebenzisa ngokuthe ngqo ii-nociceptors, ngelixa ezinye zizisa ukuqeshwa kwezinye iiseli ezithi emva koko zikhulule ezinye iiarhente zokuququzelela.17 Le nkqubo yendawo ibangela ukwanda kokuphendula yee-nociceptive neurons kwigalelo lazo eliqhelekileyo kunye / okanye ukugaywa kwempendulo kwigalelo lesiqhelo kubizwa ngokuba yi-ipipheral sensitization . Umzobo 18 ushwankathela ezinye zeendlela eziphambili ezichaphazelekayo.
Inani elikhulu labalamli abanokudumba liye lachaphazeleka ngokuthe ngqo kwintlungu yamahlombe kunye nesifo se-rotator cuff.21 25 Ngelixa abanye abalamli bemichiza basebenza ngokuthe ngqo kwii-nociceptors, uninzi lukhokelela kutshintsho kwi-neuron ye-sensory uqobo kunokuba luyenze ngqo. Olu tshintsho lunokubakho kwangoko emva kokuguqulelwa okanye ukulibaziseka ukuxhomekeka kokukhutshelwa. Imizekelo yezinto zangaphambili ziinguqu kwi-receptor ye-TRPV1 okanye kwii-ion-chated ion channels ezibangelwa yi-phosphorylation ye-protein-bound bound-protein. Imizekelo yamva ibandakanya ukonyuswa kwe-NGF kwimveliso yejelo le-TRV1 kunye nokusebenza kwe-calcium okubangelwa kukukhutshelwa kwangaphakathi.
Uvakalelo lwentlungu lusilumkisa ngokwenzakala okwenyani okanye okuzayo kwaye kubangele iimpendulo ezifanelekileyo zokukhusela. Ngelishwa, iintlungu zihlala zikhumbula ukuba luncedo njengenkqubo yokulumkisa kwaye endaweni yoko ziye zingapheli kwaye zenze buthathaka. Olu tshintsho kwisigaba esinganyangekiyo lubandakanya utshintsho ngaphakathi kwethambo lomqolo kunye nengqondo, kodwa kukwakho ukumodareyitha okumangalisayo apho imiyalezo yeentlungu iqaliswa- kwinqanaba le-neuron ye-sensory ephambili. Imizamo yokufumanisa indlela ezi-neurons ezifumanisa ngayo ukuba zivelisa iintlungu zomoya oshushu, oomatshini okanye weekhemikhali zityhile iindlela ezintsha zokubonisa kwaye zasisondeza ekuqondeni iziganeko zeemolekyuli eziququzelela utshintsho olusuka kwintlungu ukuya kwintlungu eqhubekayo.
I-Glutamate yi-neurotransmitter eyinhloko ye-excitatory kuwo onke ama-nociceptors. Ucwaningo lwengqondo ye-DRG yabantu abadala, nangona kunjalo, ibonakalisa iiklasi ezimbini ezibanzi ze-C fiber ezingabonakaliyo.
Njengoko kuchazwe ngasentla, ukulimala kuphakamisa amava ethu entlungu ngokunyusa uvelwano lwama-nociceptors ukuya kumathambo angama-thermally and mechanical stimuli. Ezi ziphumo, kwinqanaba, ukusuka kwimveliso kunye nokukhululwa kwabalamli beekhemikhali ukusuka kwisigxina sokuqala kunye neseli ezingenalo ne-neural (umzekelo, ii-fibroblasts, i-cell mast, i-neutrophils kunye neeplatelet) kwimeko yendawo36 (umzekeliso 3). Ezinye izixhobo zesobho esivuthayo (umzekelo, i-proton, i-ATP, i-serotonin okanye i-lipids) inokutshintsha i-neuronal ngokukhawuleza ngokubambisana neziteshi ze-ion kummandla we-nociceptor, kanti abanye (umzekelo, i-bradykinin kunye ne-NGF) babophelela kwiimceivers ze-metabotropic kunye ukudibanisa imiphumo yabo ngokusebenzisa isalathisi yesibini ukubonakalisa i-cascades11. Inkqubela ebonakalayo eyenziwe ekuqondeni isiseko se-biochemistry yezixhobo zokumodareyitha.
I-tissue acidosis iyimpendulo ebonakalayo yokuzilimaza, kwaye ubukhulu bentlungu okanye intlungu ehambelana nayo ihambelana kakhulu nobukhulu be-acidification37. Ukusetyenziswa kwe-asidi (i-pH 5) kwesikhumba kuvelisa ukukhutshwa okuqhubekayo kwisithathu okanye ngaphezulu kwee-nociceptors zepolymod ezingenasigxina kwintsimi ye-20.
Inkqubo yenzwa iyaphawula kwaye iguqulela uluhlu olubanzi lwezinto ezishukumisayo kunye nezomatshini kunye nokukhuseleka kwemvelo kunye nokuphela kweemichiza. Xa kunzima, ezi zinto zivelisa ubuhlungu obukhulu, kwaye kwimeko yokulimala okuqhubekayo, zombini kwiprogram kunye nendawo ye-nervous system yendlela yokudlulisa intlungu ibonisa iplastiki enkulu, ukuphucula iintlungu kunye nokuvelisa i-hypersensitivity. Xa i-plasticity ikhuthaza i-reflexes yokukhusela, inokuba luncedo, kodwa xa utshintsho oluqhubekayo, imeko yesifo esingapheliyo ingabangela. I-Genetic, i-electrophysiological, kunye nezifundo ze-pharmacological zicacisa iindlela zee molecular ezithobela ukubonwa, ukudibanisa kunye nokumodareyitha kwezinto ezixhalabisa ezenza intlungu.
Uvakalelo lomda ngakumbi kwiziphumo ezivela kutshintsho olunxulumene nokuvuvukala kwimeko yemichiza yefayibha yentsimbi (McMahon et al., 2008). Ke ngoko, ukonakala kwethishu kuhlala kuhamba nokuqokelelwa kwezinto ezingapheliyo ezikhutshwe kwii-nociceptors okanye iiseli ezingezizo ezomzimba ezihlala ngaphakathi okanye zingene kwindawo eyonzakeleyo (kubandakanya iiseli zemasti, ii-basophils, iiplatelets, ii-macrophages, i-neutrophils, iiseli zokuphela kwexesha, i-keratinocytes, kunye iifibroblast). Ngokudibeneyo. ezi zinto, zibizwa ngokuba yi- inflammatory soup , zimele uluhlu lweemolekyuli zokubonisa, kubandakanya ii-neurotransmitters, ii-peptides (iziyobisi P, CGRP, bradykinin), ii-eicosinoids kunye ne-lipids ezinxulumene noko (prostaglandins, thromboxanes, leukotrienes, endocannabinoids), ii-neurotrophins, ii-cytokines , kunye neekhemokines, kunye neeprotease zangaphandle kunye neeproton. Ngokumangalisayo, ii-nociceptors zivakalisa enye okanye nangaphezulu iiseli ezamkela indawo ezikwaziyo ukuphendula kunye nokuphendula nganye yezi arhente zepro-inflammatory okanye pro-algesic agents (Umzobo 4). Ukudibana okunjalo kukonyusa ukonwaba kwefiber ye-nerve, ngaloo ndlela iphakamisa ubuntununtunu bayo kubushushu okanye ukubamba.
Indlela engavumelekanga ngayo indlela yokunciphisa intlungu evuzayo iquka ukuvimbela ukuhlanganiswa okanye ukuqokelela kweengxenye zesobho esivuthayo. Le nto iboniswe ngokugqithiseleyo ngamachiza angenayo i-steroidal anti-inflammatory, efana ne-aspirin okanye ibuprofen, eyanciphisa intlungu yokuvuvukala kunye ne-hyperalgesia ngokuvimbela i-cyclooxygenases (i-Cox-1 kunye ne-Cox-2) ebandakanyekayo kwi-prophyglandin synthesis. Indlela yesibini kukuthintela izenzo ze-arhente ezivuthayo kwi-nociceptor. Apha, sikhankanya imizekelo esinika ingqiqo entsha kwiindlela zeselula zokukhuthaza ukuphazamiseka komzimba, okanye ukuba yintoni isiseko seendlela ezintsha zokuphulukisa intlungu.
I-NGF mhlawumbi iyayaziwa kakhulu ngendima yayo njengengxaki ye-neurotrophic efunekayo ekusindeni nasekuphuhliseni i-neurons ye-sensory ngexesha le-embryogenesis, kodwa kumntu omdala, i-NGF iphinda ikhiqizwe kwimeko yokulimala komzimba kwaye ibe yinto ebalulekileyo yesobho sokuvutha (Ritner et al., 2009). Phakathi kwezinye iithagethi zamaselula, i-NGF isebenza ngokuthe ngqo kwi-peptidergic C fiber nociceptors, ebonisa ukuxhamla kwe-NGF receptor tyrosine kinase, i-TrkA, kunye ne-faxtrophin receptor, i-P75 (i-Chao, i-2003; i-Snider noMcMahon, i-1998). I-NGF ikhiqiza ukuxhomekeka okukhulu ekutshiseni nasekukhuselweni kweendlela ngeendlela ezimbini ezahlukileyo. Ekuqaleni, ukusebenzisana kwe-NGF-TrkA kuvula iindlela ezibonakaliswe ngaphantsi kwamanzi, kuquka i-phospholipase C (PLC), i-proogen activated kinase (MAPK) kunye ne-phosphoinositide 3-kinase (PI3K). Oku kubangela ukuxhotyiswa komsebenzi weeprotheyini ezijoliswe kwi-terminal ye-nociceptor, ngokugqithiseleyo i-TRPV1, ekhokelela ekutshintsheni ngokukhawuleza kwintsebenziswano yokufudumala kwesibindi se-cellular nokuziphatha (Chuang et al., 2001).
Kungakhathaliseki ukuba zeziphi iindlela zabo ze-pro-nociceptive, ukuphazamisa i-neurotrophin okanye i-cytokine ukubonakaliswa kuye kwaba sisicwangciso esikhulu sokulawula isifo esivuthayo okanye intlungu ebangelwayo. Eyona ndlela iphambili ibandakanya ukuvala i-NGF okanye i-TNF-? isenzo nge-antibody ethomalalisayo. Kwimeko ye-TNF-?, oku kuye kwasebenza ngokuphawulekayo kunyango lwezifo ezininzi ezizimelayo, ezibandakanya i-rheumatoid arthritis, ekhokelela ekunciphiseni okumangalisayo kuzo zombini ukutshatyalaliswa kwezicubu kunye nokuhamba ne-hyperalgesia (Atzeni et al., 2005). Ngenxa yokuba izenzo eziphambili ze-NGF kwi-nociceptor yabantu abadala zenzeka kwindawo yokuvuvukala, inzuzo yale ndlela kukuba i-hyperalgesia iya kuncipha ngaphandle kokuchaphazela. qwa lasela intlungu. Enyanisweni, iintsholongwane ze-NGF zangoku zivavanyo zonyango ekwenzeni unyango oluvuthayo lwe-syndromes (Hefti et al., 2006).
Intlungu ebuhlungu ibonakaliswa ngokukhululwa kwe-glutamate ukusuka kwiimitha eziphambili zee-nociceptors, ezivelisa i-currents after-synaptic currents (EPSCs) kwinqanaba le-second order. Oku kwenzeka ngokukodwa ngokusebenzisa i-postsynaptic AMPA kunye ne-kainate subtypes ye-ionotropic receptors ionotropic. Ukuqulunqwa kwe-EPSC yesigxina kwi-neuron ye-postsynaptic ekugqibeleni kuya kubangela isenzo esingabalekayo nokuhambisa isigidimi sobuhlungu kwi-neurons ephezulu.
Ezinye iziphumo zibonisa ukuba utshintsho kwi-neuron, ngokwalo, lunegalelo kwinkqubo yokukhubaza. Ngokomzekelo, ukulimala kwentsholongwane yechungechunge kumgangatho ophantsi-ulawula i-K + - Cl-co-transporter i-KCC2, ebalulekileyo ekugcineni ii-K + kunye neeClass eziqhelekileyo kwi-membrane ye-plasma (i-Coull et al., I-2003). Ukurhoxisa i-KCC2, ebonakaliswa ku-lamina I i-neurons yokubonisa, iphumela ekutshintsheni kwi-Cl-gradient, enjengokuthi ukusebenza kwe-GABA-A i-receptors iphoxisa, kunokuxhomekeka kwe-lamina I i-neurons ye-projection. Oku kuya kuthi, kukhulise ukukhutshulwa nokunyusa intlungu. Enyanisweni, ukuvinjwa kwemithi ye-pharmacy okanye i-rRNA-mediated downregulation ye-KCC2 kwi-rat yenza i-allodynia engumatshini.
Kutheni ihlombe lam libuhlungu? Ukuhlaziywa kwe-neuroanatomical and biochemical basis of pain
UBenjan John Floyd Dean, uStephen Edward Gwilym, uAndrew Jonathan Carr
Iindlela kunye neendlela zeMolcular of Pain
UAllan I. Basbaum1, uDiana M. Bautista2, uGreory uGory Scherrer1, kunye noDavid Julius3
1Dafa ye-Anatomy, iYunivesithi yaseCalifornia, iSan Francisco 94158
I-2Department of Biology and Cell Biology, iYunivesithi yaseCalifornia, eBerkeley CA 94720 3Department of Physiology, iYunivesithi yaseCalifornia, iSan Francisco 94158
Iinkqubo ze-molecular of nociception
UDavid Julius * kunye noAllan I. Basbaum
*ISebe leSellular kunye ne-Molecular Pharmacology, kunye �ISebe le-Anatomy nePhysiology kunye ne-WM Keck Foundation ye-Integrative Neuroscience, kwiYunivesithi yaseCalifornia eSan Francisco, eSan Francisco, eCalifornia 94143, e-USA (i-imeyile: julius@socrates.ucsf.edu)
Umgangatho wobuchule wokuSebenza *
Ulwazi olulapha ku "Biochemistry Of Pain"Akujoliswanga ukuthatha indawo yobudlelwane obubodwa kunye nomntu oqeqeshiweyo wezempilo okanye ugqirha onelayisensi kwaye akusiyo isiluleko sonyango. Sikhuthaza ukuba wenze izigqibo zezempilo ngokusekelwe kuphando lwakho kunye nentsebenziswano kunye nochwepheshe bezempilo abaqeqeshiweyo.
Ulwazi lweBlog kunye neengxoxo zoMda
Umda wethu wolwazi ilinganiselwe kwiChiropractic, i-musculoskeletal, amayeza omzimba, impilo, igalelo le-etiological ukuphazamiseka kwe-viscerosomatic ngaphakathi kweentetho zeklinikhi, ezinxulumene ne-somatovisceral reflex clinical dynamics, i-subluxation complexes, imiba yezempilo ebuthathaka, kunye / okanye amanqaku amayeza asebenzayo, izihloko kunye neengxoxo.
Sibonelela kwaye sibonise intsebenziswano yeklinikhi neengcaphephe kumacandelo ahlukeneyo. Ingcali nganye ilawulwa ngumsebenzi wabo wobugcisa kunye negunya labo lokufumana iphepha-mvume. Sisebenzisa iiprothokholi ezisebenzayo zempilo kunye nempilo entle ukunyanga nokuxhasa ukhathalelo lokwenzakala okanye ukuphazamiseka kwenkqubo ye-musculoskeletal.
Iividiyo zethu, izithuba, izihloko, imixholo, kunye nokuqonda zibandakanya imiba yezonyango, imiba, kunye nezihloko eziyelelene kwaye zixhase ngokuthe ngqo okanye ngokungathanga ngqo umda wokuziqhelanisa wethu.
I-ofisi yethu izamile ngokufanelekileyo ukubonelela ngeengcaphulo ezixhasayo kwaye ichonge uphando olufanelekileyo lophando okanye izifundo ezixhasa izithuba zethu. Sinikezela ngeekopi zophando ezixhasayo ezifumanekayo kwiibhodi ezilawulayo nakuluntu ngesicelo.
Siyaqonda ukuba sigubungela imicimbi efuna inkcazo eyongezelelweyo yokuba inganceda njani kwisicwangciso esithile sokhathalelo okanye inkqubo yonyango; ke, ukuqhubeka nokuxoxa ngombandela ongentla, nceda ukhululeke ukubuza UDkt Alex Jimenez, DC, okanye qha ga mshelana nathi 915-850-0900.
Silapha ukunceda wena kunye nosapho lwakho.
Iintsikelelo
UDkt Alex Jimenez D.C., I-MSACP, RN*, I-CCST, IFMCP*, I-CIFM*, I-ATN*
email: qeqeshi@elpasofunctionalmedicine.com
Ilayisenisi njengoGqirha weChiropractic (DC) kwi Texas & New Mexico*
Texas DC Ilayisensi # TX5807, New Mexico DC Ilayisensi # I-NM-DC2182
Unikwe Ilayisensi njengoMongikazi oBhalisiweyo (RN*) in Florida
Florida License RN Ilayisensi # I-RN9617241 (Nombolo yolawulo. 3558029)
Ubume obubambeneyo: ILayisensi yeeNkcazo ezininzi: Ugunyaziswe Ukuziqhelanisa I-40 States*
UGqr. Alex Jimenez DC, MSACP, RN* CIFM*, IFMCP*, ATN*, CCST
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