鞘内注射氟代柠檬酸对神经病理性疼痛大鼠的镇痛作用

Analgesic effect of intrathecal fluorocitrate on neuropathic pain in rats

目的 通过观察鞘内注射星形胶质细胞特异性抑制剂氟代柠檬酸（FC）对神经病理性疼痛大鼠的镇痛作用，探讨脊髓星形胶质细胞在神经病理性疼痛中的作用。方法 雄性SD大鼠32只，随机分为4组（n=8），A组行假手术，鞘内注射FC的溶媒；B组行假手术，鞘内注射FC；C组制作坐骨神经慢性压迫性损伤（CCI）模型，鞘内注射FC的溶媒；D组制备CCI模型，鞘内注射FC。鞘内置管后3d，制备CCI模型，术后1d开始行鞘内注射，1次，d（容积1μl），连续6d，剂量为1mol/μl。分别于术前1d（基础值）、术后1、3、5、7d测定大鼠的机械痛阈和热痛阈。术后7d测定热痛阈后立即处死大鼠，取L4,6脊髓组织，其中4只用于免疫组化实验（测定IL-6表达），另外4只用于RT-PCR实验（测定IL-6mRNA表达）。结果 CCI可导致机械痛阈和热痛阈降低，脊髓组织IL-6 mRNA和IL-6表达增加；而鞘内注射FC可在一定程度上抑制CCI导致的上述改变。结论 脊髓星形胶质细胞的激活参与大鼠神经病理性疼痛的调节。

Objective To investigate the analgesic effect of intrathecal （IT） fluorocitrate （FC） （a selective astrecyte metabolic inhibitor） on neuropathic pain induced by chronic constrictive injury （CCI） to sciatic nerve. Methods Thirty-two adult male SD rats weighing 220-280 g were randomly divided into 4 groups （ n = 8 each）： group A sham operation ＋ （IT） vehicle; group B sham operation ＋ （IT） FC; group C CCI ＋ （IT） vehicle and group D CCI ＋ （IT） FC. IT catheter was placed under pentobarhital anesthesia according to Yan JP et al. Sciatic nerve on one side was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 catgut. FC （ 1 nmol·μl^-1） 1μl was given IT at 1 d after CCI, once a day for 6 consecutive days. Mechanical and thermal pain threshold were measured by paw withdrawal latencies to yon Frey hair and radiant heat stimulation at 1 d before operation （baseline） and 1, 3, 5, 7 d after operation. The animals were killed at 7 d after operation and the L,5 segment of the spinal cord was removed for determination of expression of IL-6 mRNA （by RT-PCR） and IL-6 protein （by i mmuno-histochemistry）. Results CCI significantly decreased the mechanical and thermal pain threshold and increased the expression of IL-6 mRNA and IL-6 protein in the ipsilateral spinal dorsal horn. IT injection of FC suppressed the increase in the expression of IL-6 mRNA and protein in the spinal cord to some extent and significantly attenuated CCI-induced mechanical and thermal hyperalgesia. Conclusion The activation of astrocytes in the spinal cord may be involved in the modulation of neuropathic pain in rat.