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

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1 d、注药后3、5、7、9、11、14、18、21 d检测大鼠机械缩爪阈值。腹腔注药前1 d、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1 d比较,C组机械缩爪阈值从紫杉醇注射后7 d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7 d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。

Changes of 5-hydroxytryptamine contents in spinal cord dorsal horns of paclitaxel induced neuropathic pain rats

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（n=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 1d 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 paia