{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:36:46Z","timestamp":1784759806326,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,8,3]],"date-time":"2012-08-03T00:00:00Z","timestamp":1343952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2013,2]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>The present study directly addresses the roles of the P2X7<\/jats:sub><\/jats:styled-content> receptor (P2X7<\/jats:sub>R<\/jats:styled-content>), an ionotropic adenosine triphosphate (ATP)<\/jats:styled-content> receptor, and cytokines in the induction of orofacial pain following chronic constriction injury (CCI<\/jats:styled-content>) of the infraorbital nerve (IoN<\/jats:styled-content>).<\/jats:p><\/jats:sec>Methods<\/jats:title>Rats were anesthetized, and ligatures of 4\u20100 chromic gut were tied around the IoN<\/jats:styled-content>. A<\/jats:styled-content>438079, a P2X7<\/jats:sub>R<\/jats:styled-content> antagonist or SB<\/jats:styled-content>203580, a phosphorylated (p)\u2010p38 mitogen\u2010activated protein kinase (MAPK<\/jats:styled-content>) inhibitor, was infused intrathecally into CCI<\/jats:styled-content>\u2010treated rats. In another group of rats, 3\u2032\u2010O\u2010(4\u2010benzoylbenzoyl) adenosine 5\u2032\u2010triphosphate (BzATP)<\/jats:styled-content>, a P2X7<\/jats:sub>R<\/jats:styled-content> agonist, was infused intrathecally with A<\/jats:styled-content>438079, SB<\/jats:styled-content>203580 or etanercept, a tumor necrosis factor (TNF<\/jats:styled-content>)\u2010\u03b1 receptor\u2010binding recombinant drug.<\/jats:p><\/jats:sec>Results<\/jats:title>CCI<\/jats:styled-content> of the IoN<\/jats:styled-content> induced tactile allodynia\/hyperalgesia and up\u2010regulation of P2X7<\/jats:sub>R<\/jats:styled-content>, membrane\u2010bound TNF<\/jats:styled-content>\u2010\u03b1 (mTNF\u2010\u03b1) and soluble TNF<\/jats:styled-content>\u2010\u03b1 (sTNF<\/jats:styled-content>\u2010\u03b1) in the trigeminal sensory nuclear complex (TNC<\/jats:styled-content>). Tactile allodynia\/hyperalgesia or up\u2010regulation of mTNF\u2010\u03b1 and sTNF<\/jats:styled-content>\u2010\u03b1 in the TNC<\/jats:styled-content> following CCI<\/jats:styled-content> of the IoN<\/jats:styled-content> was inhibited by A<\/jats:styled-content>438079. SB<\/jats:styled-content>203580 also attenuated tactile allodynia\/hyperalgesia or up\u2010regulation of mTNF<\/jats:styled-content>\u2010\u03b1, but not the up\u2010regulation of sTNF<\/jats:styled-content>\u2010\u03b1 in the TNC<\/jats:styled-content>. Treatment of rats with BzATP<\/jats:styled-content> induced tactile allodynia\/hyperalgesia and up\u2010regulation of sTNF<\/jats:styled-content>\u2010\u03b1 and p\u2010p38 in the TNC<\/jats:styled-content>. Tactile allodynia\/hyperalgesia or up\u2010regulation of sTNF<\/jats:styled-content>\u2010\u03b1 following BzATP<\/jats:styled-content> treatment was inhibited by SB203580 and etanercept.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Based on these findings, phosphorylation of p38 MAPK<\/jats:styled-content> via P2X7<\/jats:sub>R<\/jats:styled-content> may induce tactile allodynia\/hyperalgesia, which is most likely mediated by sTNF<\/jats:styled-content>\u2010\u03b1 released by microglia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/j.1532-2149.2012.00174.x","type":"journal-article","created":{"date-parts":[[2012,8,3]],"date-time":"2012-08-03T18:50:09Z","timestamp":1344019809000},"page":"185-199","source":"Crossref","is-referenced-by-count":30,"title":["P2X7<\/sub><\/scp> receptor in the trigeminal sensory nuclear complex contributes to tactile allodynia\/hyperalgesia following trigeminal nerve 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