普瑞巴林可通过抑制TRPV1以缓解神经病理性疼痛

Pregabalin relieves neuropathic pain by inhibiting TRPV1

目的探讨普瑞巴林(pregabalin,PGB)缓解神经病理性疼痛的潜在机制。方法构建常用的神经病理性疼痛模型——大鼠慢性坐骨神经缩窄损伤模型(chronic constriction injury,CCI),给予PGB或瞬时阳离子通道亚家族V成员1蛋白受体(the transient receptor potential cation channel subfamily V member 1,TRPV1)的抑制剂辣椒平(capsazepine,CPZ)或TRPV1的激动剂辣椒素(capsaicine,CP)以观察PGB的镇痛效果。运用免疫组化和免疫印迹法检测与疼痛正相关的TRPV1蛋白在CCI大鼠脊髓中的表达。结果PGB和TRPV1的抑制剂CPZ都能有效地提高CCI大鼠模型的痛阈(P<0.05),CPZ+PGB和CPZ的镇痛作用差异无统计学意义(P>0.05)。免疫组化和免疫印迹结果均显示PGB可减低CCI模型大鼠脊髓中TRPV1蛋白的表达。同时给予PGB和TRPV1激动剂CP干预CCI大鼠后,CCI+PGB+CP组痛阈低于CCI+PGB组(P<0.05),且与CCI组比较差异无统计学意义(P>0.05)。结论PGB可通过抑制TRPV1蛋白的表达而缓解神经病理性疼痛。

Objective To explore the underlying mechanisms of pregabalin(PGB)in reliving neuropathic pain.Methods The common neuropathic pain models,chronic narrow sciatic nerve injury model of rats(chronic constriction injury,CCI),were established firstly.PGB,chili flat(capsazepine CPZ),the transient receptor potential action channel subfamily V member 1(TRPV1)inhibitor or TRPV1 activator capsaicine(CP),were given to the CCI rats to observe the analgesic effect of PGB.Immunohistochemistry and western blotting were used to detect the protein expression of TRPV1 in spinal cord of CCI rats.Results Both PGB and CPZ(TRPV1 inhibitor)effectively improved the pain threshold of CCI rats(P<0.05).No statistically significant difference in analgesic effect between CPZ+PGB and CPZ(P>0.05).Immunohistochemistry and western blotting results showed that PGB reduced TRPV1 protein expression in spinal cord of CCI rats.The pain threshold of CCI+PGB+CP group,which accepted both PGB and TRPV1 activator CP,was lower than that in CCI+PGB group(P<0.05).The pain threshold was lower in the CCI+PGB+CP group than that in the CCI+PGB group(P<0.05),and there was no significant difference compared with the CCI group(P>0.05).Conclusion PGB could relive neuropathic pain by inhibiting TRPV1 protein expression.