米诺环素治疗外周神经损伤所致神经病理性痛的时间窗

The therapeutic time window of minocycline for treating peripheral nerve injury-induced neuropathic pain

目的探讨米诺环素治疗外周神经损伤所致的神经病理性痛的作用机制及其时间窗。方法通过行为药理学方法证实鞘内注射米诺环素对大鼠脊神经结扎(spinal nerve ligation,SNL)所导致的神经病理性痛的镇痛作用以及其作用时间窗,并通过免疫荧光化学方法观察脊髓背角小胶质细胞的活化变化。结果脊神经结扎后盐水对照组动物出现明显的神经病理性痛,同时形态学结果显示脊髓背角小胶质细胞明显活化;脊神经结扎术后1、3、7d鞘内注射米诺环素,与盐水组对比可有效减轻神经病理性痛,同时可以抑制脊髓背角小胶质细胞的活化;脊神经结扎后10、21d鞘内注射米诺环素,与盐水组比较虽能够抑制小胶质细胞的活化,但却不能缓解神经病理性痛。假手术组无论是鞘内给予米诺环素还是生理盐水都不影响动物的痛行为学变化以及脊髓背角的形态学变化。结论鞘内注射米诺环素可以通过抑制脊髓背角小胶质细胞活化治疗外周神经损伤所致的神经病理性痛,其治疗时间窗为神经病理性痛发生的早期。

Objective To investigate the therapeutic effect and time window of minocycline on peripheral nerve injury-induced neuropathic pain.Methods The present study intended to confirm the effect of post-injury intrathecal minocycline on neuropathic pain induced by L5 spinal nerve ligation（SNL） and the therapeutic time window with behavioral tests in rats.Moreover,microglial activation after intrathecal minocycline was determined by immunohistochemistry.Results Post-injury intrathecal minocycline could attenuate mechanical allodynia effectively and inhibit spinal microglial activation on postoperative day（POD） 1,POD 3 and POD 7 compared with those of SNL-saline group.Additionally,results from POD 10 and POD 21 showed that intrathecal minocycline suppressed spinal microglial activation but could not reverse mechanical allodynia.In the sham-operation group neither intrathecal minocycline nor normal saline affected the rats＇ pain-related behavior or morphological changes of spinal microglia.Conclusion Post-injury intrathecal minocycline is an effective therapeutic intervention for treating SNL-induced neuropathic pain by inhibiting spinal microglia activation.Accordingly,there is indeed a therapeutic time window for post-injury intrathecal minocycline,which is the initiation stage of SNL-induced neuropathic pain.