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本研究旨在研究螺环哌嗪季铵盐化合物LXM-15抗完全弗氏佐剂引起的慢性炎性痛,及慢性坐骨神经压迫损伤(CCI)引起的慢性神经病理性疼痛的作用及机制.结果 表明,在慢性炎性疼痛模型中,给予LXM-15后,小鼠足肿胀、踝肿胀明显减轻;机械缩足阈值和热痛敏缩足潜伏期明显增加.用外周烟碱受体拮抗剂六烃季铵,或α7烟碱受体拮抗剂甲基牛扁亭预处理,可阻断LXM-15的抗慢性痛作用.在慢性神经病理性疼痛模型中,LXM-15能明显缓解CCI大鼠的机械刺激痛和热刺激痛觉过敏.进一步研究显示,LXM-15可明显抑制CCI大鼠背根神经节中JAK2和STAT3蛋白的磷酸化,以及TNF-α和c-fos mRNA的表达.综上所述,本研究表明LXM-15可缓解啮齿类动物的慢性炎性疼痛和慢性神经病理性疼痛.其作用机制可能是通过激活外周α7烟碱受体,进一步抑制JAK2/STAT3信号通路,降低TNF-α和c-fos的表达.“,”In the present study,we aimed to evaluate the effect of the spirocyclopiperazinium salt compound LXM-15 on chronic inflammatory pain and chronic neuropathic pain induced by complete Freund's adjuvant (CFA) or chronic constriction injury (CCI) in mice and rats.The results showed that administration with LXM-15 significantly reduced paw edema and ankle swelling and increased the mechanical withdrawal threshold and paw withdrawal latency after CFA injection in mice.LXM-15 significantly alleviated the mechanical allodynia and thermal hyperalgesia in CCI rats.The effect was abolished by pretreatment with hexamethonium (a peripheral nAChR antagonist) or methyllycaconitine citrate (an αt7 nAChR antagonist).Furthermore,LXM-15 significantly inhibited the phosphorylation of JAK2 and STAT3,and suppressed the expressions of TNF-α and c-fos in dorsal root ganglia of CCI rats.Collectively,we reported that LXM-15 relieved chronic inflammatory pain in CFA mice and chronic neuropathic pain in CCI rats.The underlying mechanism might be related to the activation of peripheral α7 nicotinic receptor,further inhibiting JAK2/STAT3 signaling pathway,and eventually suppressing the expressions of TNF-α and c-fos.