P2X7 receptor in the trigeminal sensory nuclear complex contributes to tactile allodynia/hyperalgesia following trigeminal nerve injury. (3rd August 2012)

• Record Type: Journal Article
• Authors: Ito, G.; Suekawa, Y.; Watanabe, M.; Takahashi, K.; Inubushi, T.; Murasaki, K.; Hirose, N.; Hiyama, S.; Uchida, T.; Tanne, K.
• Is Part Of: European journal of pain. Volume 17:Number 2(2013)
• Page Start: 185
• Page End: 199
• Publication Date: 2012-08-03
• Subjects: Pain -- Periodicals; Pain -- Treatment -- Periodicals; Pain -- Physiological aspects -- Periodicals; 616.0472
• DOI: 10.1002/j.1532-2149.2012.00174.x
• Languages: English
• ISSNs: 1090-3801

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="ejp174-sec-0003" sec-type="section"> <title>Background</title> <p>The present study directly addresses the roles of the P2X<sub>7</sub> receptor (P2X<sub>7</sub>R), an ionotropic adenosine triphosphate (ATP) receptor, and cytokines in the induction of orofacial pain following chronic constriction injury (CCI) of the infraorbital nerve (IoN).</p> </sec> <sec id="ejp174-sec-0004" sec-type="section"> <title>Methods</title> <p>Rats were anesthetized, and ligatures of 4‐0 chromic gut were tied around the IoN. A438079, a P2X<sub>7</sub>R antagonist or SB203580, a phosphorylated (p)‐p38 mitogen‐activated protein kinase (MAPK) inhibitor, was infused intrathecally into CCI‐treated rats. In another group of rats, 3′‐O‐(4‐benzoylbenzoyl) adenosine 5′‐triphosphate (BzATP), a P2X<sub>7</sub>R agonist, was infused intrathecally with A438079, SB203580 or etanercept, a tumor necrosis factor (TNF)‐α receptor‐binding recombinant drug.</p> </sec> <sec id="ejp174-sec-0005" sec-type="section"> <title>Results</title> <p>CCI of the IoN induced tactile allodynia/hyperalgesia and up‐regulation of P2X<sub>7</sub>R, membrane‐bound TNF‐α (mTNF‐α) and soluble TNF‐α (sTNF‐α) in the trigeminal sensory nuclear complex (TNC). Tactile allodynia/hyperalgesia or up‐regulation of mTNF‐α and sTNF‐α in the TNC following CCI of the IoN was inhibited by A438079. SB203580 also attenuated tactile allodynia/hyperalgesia or up‐regulation of mTNF‐α, but not the up‐regulation of sTNF‐α in the TNC. Treatment of rats with BzATP induced tactile allodynia/hyperalgesia and up‐regulation of sTNF‐α and p‐p38 in the TNC. Tactile allodynia/hyperalgesia or up‐regulation of sTNF‐α following BzATP treatment was inhibited by SB203580 and etanercept.</p> </sec> <sec id="ejp174-sec-0006" sec-type="section"> <title>Conclusions</title> <p>Based on these findings, phosphorylation of p38 MAPK via P2X<sub>7</sub>R may induce tactile allodynia/hyperalgesia, which is most likely mediated by sTNF‐α released by microglia.</p> </sec> </abstract>