鞘内联合应用白细胞介素-1受体拮抗剂、氯胺酮对慢性神经病理性疼痛的影响

目的 观察白细胞介素-1受体拮抗剂(interleukin-1 receptor antagonist,IL-1ra)与氯胺酮联合应用对慢性神经病理性疼痛的影响. 方法 采用大鼠坐骨神经慢性压迫性损伤(chronic constriction injury,CCI)模型.雄性SD大鼠40只,按完全随机原则随机分为假手术组、CCI组、IL-1ra组、氯胺酮组、IL-1ra+氯胺酮组.各实验组造模后,分别于第21天鞘内注射前2 h及注射后第2、4、6小时,采用von Frey纤维丝和热痛刺激仪检测大鼠机械性缩爪潜伏期(mechanical withdrawal threshold,MWT)和热痛缩爪潜伏期(thermal withdrawal latency,TWL),应用免疫组织化学及Western blot方法检测脊髓背角神经元磷酸化细胞外信号调节蛋白激酶(phospho-extracellular signal-regulated kinase ,p-ERK)表达的情况. 结果 与CCI组相比,鞘内联合应用IL-1rα+氯胺酮组,明显减轻神经病理痛大鼠的痛行为,给药2h后MWT(7.1±2.2)显著升高,TWL(13.5±3.6)显著延长,其效应持续至给药后6 h(P<0.01).脊髓背角p-ERK表达明显减少(P<0.01),免疫组化p-ERK阳性细胞数也明显减少(P<0.01).同时比单独高剂量应用各药物效应有增强的趋势. 结论 IL-1ra与氯胺酮在较低剂量联合应用能明显减轻神经病理性疼痛,与降低p-ERK表达有关.

Intrathecal injection of IL-1ra and ketamine for chronic neuropathic pain model in rats

objective To observe the effect of intrathecal injection of IL-1ra and ketamine for chronic constriction injury (CCI)in rats. Methods 40 male SD rats were randomly divided into 5 groups: Sham operation group;CCI group; IL-1ra group;ketamine group; IL-1ra and ketamine group. Thermal withdrawal latency (TWL) and mechanical withdrawal threshold(MWT) of 2 h pre -drug and 2,4,6 h after injected drugs at day 21 in rats were performed by Hargreave's thermal radiation apparatus and von Frey's method of micro filament, respectively. The rats were killed after the behavior test was finished. The expression of p-ERK was measured in the spinal cord by immunohistochemical analysis and western blot method. Results The group of combined injection IL-1rα and ketamine produced significantly more potent analgesia compared with that of CCI group. MWT(7.1±2.2 )and TWL ( 13.5 ±3.6)were increased from 2 hours to 6 hours after intrathecal injection of IL-1rα and ketamine(P<0.01 ). The expressions of p-ERK and the number of positive cells in the combined injection group were significantly lower than that of CCI group (P<0.01). The effect of IL-1ra and ketamine in lower dosages is tendency enhanced than that of higher dosage alone. Conclusion The combined injection of IL-lra and ketamine in lower dosage can produce synergistic abirritation in chronic pain.