背根神经节8型代谢型谷氨酸受体对神经病理性疼痛的影响

Role of dorsal root ganglion metabotropic glutamate receptor 8 in neuropathic pain

目的探讨背根神经节8型代谢型谷氨酸受体(mGluR8)对神经病理性疼痛的影响。方法取雄性Sprague-Dawley大鼠60只,随机分入假手术组和神经病理性疼痛模型组(简称模型组),术后7d模型确立后将两组各分为3个亚组,分别鞘内注射0.9%氯化钠、S-3,4-二羧基苯氨基乙酸(S-DCPG)、α-甲基-O-磷酸丝氨酸(MSOP)+S-DCPG,用vonFrey纤维丝测定大鼠给药后的机械刺激缩足反应阈值(PWMT),采用Western印迹法检测脊髓和背根神经节mGluR8的表达。结果假手术组及其3个亚组在术后7d和给药后30min的PWMT与同组术前的差异均无统计学意义(P值均>0.05),假手术组及其3个亚组在术前、术后7d和给药后30min同时间点组间PWMT的差异亦均无统计学意义(P值均>0.05)。模型组及其3个亚组术后7d和给药后30min的PWMT均显著低于同组术前(P值均<0.01);模型组S-DCPG亚组给药后30min的PWMT显著高于模型组0.9%氯化钠亚组同时间点(P<0.05),模型组MSOP+S-DCPG亚组与模型组0.9%氯化钠亚组间给药后30min的PWMT的差异无统计学意义(P>0.05),模型组及其3个亚组间术前、术后7d同时间点PWMT的差异均无统计学意义(P值均>0.05)。假手术组与模型组间术前PWMT的差异无统计学意义(P>0.05),模型组术后7d和给药后30min的PWMT均显著低于假手术组同时间点(P值均<0.01)。Western印迹法结果显示,模型组背根神经节mGluR8受体的相对表达量(0.72±0.12)显著低于假手术组(1.00±0.19,P<0.05)。模型组和假手术组的脊髓内均未检测到mGluR8受体的表达。结论激活背根神经节mGluR8可以缓解神经病理性疼痛大鼠的痛觉过敏,神经病理性疼痛形成过程中背根神经节mGluR8表达下调。

Objective To investigate the role of dorsal root ganglion metabotropic glutamate receptor 8 （mGluR8） in neuropathic pain. Methods Sixty male Sprague-Dawley rats were randomized into neuropathic pain group and sham operation group. The reliability of the model was certified at day 7 after surgery. Then each group was divided into 3 subgroups （intrathecal injection of normal saline, S-3,4-Dicarboxyphenylglycine [S-DCPG] and α-methytserine-O-phosphate[MSOP] ＋ S-DCPG, respectively）. Paw withdrawal mechanical threshold （PWMT） was assessed by von Frey test. The expressions of mGluR8 both in the spinal cord and dorsal root ganglion were evaluated by Western blotting. Results In the sham operation group, compared with preoperative PWMT, there was no significant change in PWMT at day 7 after operation and 30 min after intrathecal injection of normal saline, S-DCPG or MSOP＋ S-DCPG （all P〈0.05）. In the neuropathic pain group, PWMT at day 7 after operation and 30 min after intrathecal injection of normal saline, S-DCPG or MSOP＋S-DCPG were significantly lower than preoperative ones （all P〈0.01 ） ; the intrathecal injection of S-DCPG significantly increased PWMT compared with the intrathecal injection of normal saline （P〈0.05）, but the intrathecal injection of MSOP＋ S-DCPG produced no effect compared with the normal saline （P ~ 0. 05）~ there was no significant difference in PWMT between subgroups （all P〉0.05）. There was no significant difference in preoperative PWMT between sham operation group and neuropathic pain group （P〉0.05）. However, PWMT in neuropathic pain group was significantly lower than that in sham operation group at day 7 after operation and 30 min after drug injection （both P〈0.01 ）. Western blotting results showed that relative expression of mGluR8 in dorsal root ganglion in neuropathic pain group was significantly lower than that in sham operation group （0.72±0.12 vs. 1.00±0.19, P〈0.05）, but mGluR8 was not found in spinal cord in both groups. Conclusion Activation of dorsal root ganglion mGluR8 can attenuate hyperalgesia in neuropathic pain rats. The expression of dorsal root ganglion mGluR8 is significantly reduced in neuropathic pain rats.