Cyclooxygenase inhibitors suppress the expression of P2X(3) receptors in the DRG and attenuate hyperalgesia following chronic constriction injury in rats.
Recent evidence suggests that P2X(3) receptors express abundantly in nociceptive sensory neurons and play an important role in neuropathic pain. Upregulation of prostaglandin E2 (PGE2) after nerve injure is involved in the pathogenesis of neuropathic pain. An increase of P2X(3) receptors after chronic constriction injury (CCI) to the sciatic nerve has also been reported, the mechanisms are not known clearly. In this study, we examined the effects of systemic administration of cyclooxygenase (COX) inhibitors on analgesia and the expression of P2X(3) receptors in the dorsal root ganglia (DRG) in CCI rats. Rats received 0.9% saline, the nonselective COX inhibitor ibuprofen (40mgkg(-1)day(-1)) or the selective COX-2 inhibitor celecoxib (30mgkg(-1)day(-1)) by gavage twice daily from 3 to 14 days after surgery. Mechanical allodynia and thermal hyperalgesia induced by CCI were markedly attenuated by celecoxib from 5 to 14 days after surgery, and relieved by ibuprofen treatment from 7 to 10 days after surgery. The increase of P2X(3) receptors in the DRG in CCI rats on day 14 after surgery was also significantly inhibited; the effect of ibuprofen was stronger than that of celecoxib. These results demonstrate that up-regulated COX/PGE2 after nerve damage may play an important role in neuropathic pain. They are highly involved in the expression of P2X(3) receptors in the DRG in CCI rats.
Wang
Ying
Y
Department of Anesthesiology, Xiangya Hospital of Central-South University, Hunan 410008, China.
Zhang
Xiang
X
Guo
Qu-Lian
QL
Zou
Wang-Yuan
WY
Huang
Chang-Sheng
CS
Yan
Jian-Qin
JQ
D000818:Animals; D000068579:Celecoxib; D003251:Constriction, Pathologic / Q000150:complications; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D005727:Ganglia, Spinal / Q000378:metabolism*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D007052:Ibuprofen / Q000627:therapeutic use; D008297:Male; D011720:Pyrazoles / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis*; D058477:Receptors, Purinergic P2X3; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism*; D013449:Sulfonamides / Q000627:therapeutic use; D014110:Touch
D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D013449:Sulfonamides; D000068579:Celecoxib; D007052:Ibuprofen