脊髓糖皮质激素受体在神经病理性疼痛中的作用

Role of spinal glucocorticoid receptor in neuropathic pain

目的观察脊髓背角糖皮质激素受体(glucocorticoid receptor,GR)在慢性病理性神经痛中的作用。方法成年SD大鼠分为假手术组、坐骨神经慢性压迫损伤(CCI)组、CCI+生理盐水组、CCI+RU38486治疗组。测定各组大鼠不同时间点热缩足反射潜伏期(TWL);CCI组于术后7、14 d处死大鼠,取L4～L6脊髓冰冻切片,应用免疫组织化学方法观察GR表达变化;大鼠蛛网膜下腔埋管,于CCI术后1～14 d鞘内注射生理盐水、GR拮抗剂RU38486,测定其对TWL的影响。结果 CCI大鼠术后1 d损伤侧下肢TWL即显著降低,到第14天热疼敏仍持续存在;术后7、14 d损伤侧L4～L6节段脊髓背角GR表达显著增加(P<0.05);术后1～14 d鞘内给予GR拮抗剂RU38486可明显减轻CCI所致的热疼敏。结论脊髓背角糖皮质激素受体的激活可促进坐骨神经慢性压迫损伤所致的神经痛的发生和维持。

Objective To investigate the role of spinal glucocorticoid receptor（GR） in the generation and development of chronic neuropathic pain.Methods Healthy adult SD rats were divided into a sham group,a chronic compressive injury of sciatic nerve（CCI） group,a CCI＋saline group and a CCI＋RU38486 group.The thermal withdrawal latency（TWL） was measured before operation and at 1,3,7 and 14 d after operation.The L4-6 lumbar segment of spinal cord of the rats in the CCI group was separated for the determination of GR expression by immunohistochemical assay.For the rats of the CCI＋saline group and the CCI＋RU38486 group,saline and RU38486（GR antagonist） were intrathecally administered twice a day for 14 d after CCI operation.Results TWL decreased at 1 d after CCI operation,and thermal hyperalgesia persisted until the end of the experiment.The immunohistochemical results showed that the expression of GR significantly increased in the ipsilateral dorsal horn at 7 and 14 d after CCI operation.However,the intrathecal administration of RU38486 could significantly suppress the decrease of TWL after CCI operation.Conclusion The activation of GR in spinal dorsal horn can promote the pathogenesis of neuropathic pain,suggesting that blocking GR may be a viable therapeutic strategy for neuropathic pain.