紫杉醇诱导神经病理性疼痛大鼠脊髓背角5-羟色胺含量变化

摘要

Objective To investigate the changes of 5-hydroxytryptamine (5-HT) contents in spinal cord dorsal horns of paclitaxel induced neuropathic pain rats. Methods Fifty-four male SD rats weighing about 300 g were randomly divided into 3 groups (? = 18): normal control group (group A); vehicle group (group B) and paclitaxel group (group C). Rats in group C were injected intraperitoneally with paclitaxel 1. 0 mg-kg^1 "d"1 to induce peripheral neuropathic pain. Mechanical withdrawal thresholds (MWT) were measured on 1 d before drug injection, 3, 5, 7, 9, 11, 14, 18 and 21 d after injection. Four rats in each group were sacrificed on Id before and 7, 14 and 21 d after paclitaxel injection. 5-HT contents in dorsal horns of spinal cord were assayed using high performance liquid chromatography with fluorescence detector. Right sciatic nerves of rats were collected on the 14th day after paclitaxel injection; transmission electron microscope was used to observe the damage of sciatic nerves. Results Compared with group A and B, MWTs in group C decreased significantly on day 7 and continued to 21st day after injection (P<0. 05). Electron photomicrographs of the sciatic nerves showed damage of nerve fibers 14d post drug injection in group C, while there was no destruction in the groups A and B. Compared with group A and B, 5-HT in group C were significantly upregulated from the 7th till 21st day after drug injection (P<0. 05). 5-HT in group C showed a strong negative linear correlation with mechanical withdrawal thresholds (r=-0. 981, P< 0. 05). Conclusion Paclitaxel induced significant upregulation of 5-HT in spinal cord dorsal horn in rats, which might play a role in the pathogenesis of paclitaxel induced neuropathic pain.%目的 观察紫杉醇诱导神经病理性疼痛大鼠脊髓背角5-羟色胺(5-HT)含量变化.方法 雄性SD大鼠54只,体重约300 g,随机均分为正常对照组(A组)、紫杉醇溶媒组(B组)和紫杉醇组(C组).分别于腹腔注药前1d、注药后3、5、7、9、11、14、18、21d检测大鼠机械缩爪阈值.腹腔注药前1d、注药后7、14、21 d每组各处死大鼠4只,取脊髓腰膨大背角组织,用高效液相色谱荧光法测定5-HT含量.腹腔注药后14 d取大鼠右侧坐骨神经,透射电镜观察神经病变情况.结果 与注药前1d比较,C组机械缩爪阈值从紫杉醇注射后7d开始显著降低,并持续至注药后21 d达最低值(P＜0.05),且显著低于A、B组(P＜0.05).坐骨神经超微结构C组纤维髓鞘板层结构松散,排列紊乱、肿胀变形、厚薄不均,A和B组大鼠坐骨神经未见异常.C组脊髓背角5-HT含量注药后7d开始显著升高,并持续至注射后21 d达最高值(P＜0.05),且显著高于A、B组(P＜0.05).C组大鼠脊髓背角5-HT含量与机械缩爪阈值呈显著线性负相关(r=-0.981,P＜0.05).结论 紫杉醇诱导的神经病理性疼痛大鼠脊髓背角组织中5-HT含量表达上调,该变化可能参与了紫杉醇所致神经病理性疼痛的发病机制.