P2X4 receptor and brain-derived neurotrophic factor in neuropathic pain |
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Authors: | Yan Xiaodi Zhou Shuangqiong Chen Qianbo Chen Chengwen Yuan Hongbin |
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Institution: | Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China |
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Abstract: | ObjectiveTo investigate whether the activation of p38MAPK is involved in the neuropathic pain induced by P2X4 receptor, and the effects of activated P2X4 receptor and p38MAPK on expression of brain-derived neurotrophic factor (BDNF) in the chronic neuropathic pain.MethodsLumbar intrathecal catheters were chronically implanted in male Sprague-Dawley rats. The right sciatic nerve was loosely ligated proximal to the sciatica's trifurcation at approximately 1.0 mm intervals with 4-0 silk sutures. The microglia inhibitor minocycline, P2X4 antagonist (TNP-ATP) and p38MAPK inhibitor (SB203580) were intrathecally administered every 12 h, 3 d post- chronic constriction injury (CCI). Mechanical nociceptive thresholds were assessed with the paw withdrawal threshold (PWT) to von Frey filaments. The expression of P2X4 and BDNF were assessed by both immunohistochemical analysis and RT-PCR.ResultsIntrathecal injection of minocycline or TNP-ATP or SB203580 significantly attenuated CCI-induced mechanical allodynia. The time courses of P2X4 receptor and BDNF expression were increased at all points after CCI and reached a peak level on postoperative d 7. Intrathecal injection of minocycline or TNP-ATP or SB203580 markedly suppressed the increase of CCI-induced P2X4 receptor and BDNF expression in the spinal cord.ConclusionThe activation of P2X4 receptor BDNF pathways contributes to neuropathic pain in CCI rats, and the activation of p38MAPK is involved in the neuropathic pain induced by P2X4 receptor. |
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Keywords: | Microglia P2X4 receptor Brain-derived neurophic factor p38 mitogen-activated protein kinases Neuropathic pain |
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