氯胺酮对大鼠脊神经结扎神经病理性痛的作用

Effects of ketamine on spinal nerve ligation-induced neuropathic pain

目的探索鞘内注射氯胺酮能否通过抑制小胶质细胞的活化而治疗神经病理性痛。方法利用大鼠脊神经结扎(spinal nerve ligation,SNL)神经病理性痛模型,并鞘内注射氯胺酮,应用von Frey行为测试观察对大鼠基础痛阈和SNL所诱导的神经病理性痛的影响;通过免疫组织化学法检测其对大鼠脊髓背角小胶质细胞活化的影响。结果鞘内注射氯胺酮能够降低SNL诱导的机械性痛觉增敏,但对正常大鼠的机械性基础痛阈没有显著影响。同时鞘内注射氯胺酮能抑制SNL所诱导的大鼠脊髓背角小胶质细胞的活化,结合荧光强度半定量检测,观察到鞘内注射氯胺酮可以降低SNL诱导的小胶质细胞活化特异性标记物OX-42的表达。结论氯胺酮治疗神经病理性痛的镇痛机理可能是通过抑制神经损伤后小胶质细胞的活化。

Objective To investigate whether ketamine can prevent microglia activation and thus exert its analgesic effect in neuropathic pain conditions.Methods Based on the spinal nerve ligation(SNL) neuropathic pain model,we first investigated the anti-nociceptive effects of intrathecal(i.t.) ketamine on basal pain threshold and SNL-induced neuropathic pain by behavioral study with von Frey filaments.Then we detected the related microglia activation levels after ketamine administration on SNL or normal rats by immunohistochemistry.Results Behavioral study indicated that ketamine i.t.attenuated SNL-induced mechanical allodynia without affecting the basal paw withdrawal threshold.Immunohistochemistry indicated that ketamine i.t.relieved SNL-induced marked microglia activation in the ipsilateral spinal dorsal horn.Together with the semi-quantification of the immunoreactive density,it was shown that ketamine i.t.inhibited SNL-induced microglia activation by attenuating the up-regulation of OX-42.Conclusion Suppressing nerve injury-induced microglia activation could be a novel mechanism of the anti-allodynia effect of ketamine on neuropathic pain.