脊髓小胶质细胞激活对SNI模型大鼠神经病理性疼痛的影响

目的观察小胶质细胞对大鼠坐骨神经分支选择性损伤(SNI)所致神经病理性疼痛的影响。方法选择雄性SD大鼠64只,随机分为4组(n=16):假手术组(Sh组);模型组(SNI组);模型 米诺环素40mg/kg组(Mb组);模型 米诺环素10mg/kg组(Ms组)。其中Mb和Ms组从造模前1d起连续7d每日2次腹腔注射相应剂量的米诺环素。分别记录全组动物在术前1d及术后1,3,5,7,14d的机械缩足反射阈值(MWT)和热缩足反射持续时间(TWD)作为大鼠疼痛行为学指标;各组大鼠分别在术后1,3,5,7,14d随机选取4只处死,取脊髓,用免疫荧光的方法检测脊髓小胶质细胞标志物OX-42的表达。结果SNI组从术后1d起即出现明显MWT降低和TWD延长,与术前及Sh组术后各时点比较均有统计学差异(P<0.05);Mb组和Ms组与SNI组相应时点比较MWT降低和TWD延长程度有显著性差异(P<0.05);Mb与Ms组比较MWT降低和TWD延长程度有统计学差异(P<0.05);Mb、Ms组与SNI组比较脊髓OX-42的表达减少,并呈剂量依赖性。结论米诺环素腹腔注射可剂量依赖性的减少OX-42的表达,抑制脊髓小胶质细胞的激活,减轻痛觉超敏和痛觉过敏,提示小胶质细胞的活化参与SNI神经病理痛的形成。

Effect of Microglia Activation on Neuropathic Pain in Rat SNI Model

Objective To investigate the effect of microglia on neuropathic pain in rat model of spared nerve injury (SNI). Methods Sixty-four SD rats were randomly assigned to 4 groups: sham operation group (Sh group),SNI model group (SNI group),40 mg/kg minocyline group (Mb group),and 10 mg/kg minocyline group (Ms group). The rats in Mb and Ms groups were intraperitoneally injected with minocyline twice daily,beginning from 1 day before nerve transection and lasting for 7 days. The mechnical withdraw threshold (MWT) and thermal withdraw duration (TWD) were recorded 1 day before surgery and 1,3,5,7,and 14 days after surgery. The expression of OX-42 in spinal microglia was detected by immunofluorescence. Results MWL decreased and TWL prolonged significantly since 1 day after surgery in SNI group,and the differences in MWL and TWL were significant between Sh and SNI groups at each time point (P < 0.05). There were significant differences in MWT and TWL between Mb and SNI groups,between Ms and SNI groups,and between Mb and Ms groups (P < 0.05). Compared with SIN group,the expression of OX-42 decreased in Mb and Ms groups in a dose-dependent manner. Conclusion The minocyline injected intraperitoneally could decrease the expression of OX-42 in a dose-dependent manner,inhibit the activation of microglia,and alleviate mechanical hyperalgesia and thermal hyperalgesia. It suggests that activated microglia participates in the formation of neuropathic pain after SNI.