白细胞介素-2对小鼠神经病理性痛的镇痛作用

The analgesic effect of interleukin-2 in the neuropathic pain mice

目的探讨白细胞介素-2(IL-2)对神经病理性痛的镇痛作用及其可能的机制,为临床治疗神经病理性痛筛选新的镇痛药物奠定基础。方法通过结扎雄性C57BL/6小鼠单侧L5/L6脊神经建立神经病理性痛模型,然后利用机械刺激和冷刺激诱发的痛觉超敏实验分别观察腹腔注射不同剂量(1.0×106、2.5×106、5.0×106u/kg)IL-2对疼痛模型小鼠患侧脚掌痛阈的影响;同时,通过5.0×106u/kg IL-2注射前30 min腹腔注射纳洛酮(1 mg/kg)以观察阿片受体拮抗剂对IL-2镇痛作用的影响。结果腹腔注射IL-2可产生剂量依赖性镇痛作用,其中5.0×106u/kg和2.5×106u/kg IL-2均可显著提高模型小鼠患侧脚掌的50%缩足阈值(P<0.01)和降低5 min抬足次数(P<0.05),镇痛效应分别维持30 min和15 min,而1.0×106u/kg IL-2无明显的镇痛作用。IL-2产生的镇痛效应不能被纳洛酮阻断。结论IL-2对小鼠神经病理性痛具有镇痛作用,其镇痛效应除受阿片受体介导外还可能有其他分子参与。

Objective To investigate the analgesic effect and possible mechanisms of interleukin-2 （IL-2） on the neuropathic pain, and to screen the novel drug for neuropathic pain diseases. Methods Male C57BL/6 mice whose unilateral LS/L6 spinal nerves were ligated were used as a neuropathic pain model. The pain thresholds of paw ipsilateral to the nerve injury before and after intraperitoneal （i. p. ） injection of different doses of IL-2 （1.0 ×10^6u/kg, 2.5 × 10^6 u/kg and 5.0 ×10^6 u/kg） were measured by the mechanical and cold stimuli. Opioid receptor antagonist naloxone （1 mg/kg）, 30 min prior to the administration of 5.0×10^6u/kg of IL-2, was given to investigate the influence of naloxone on the analgesic effect induced by IL-2. Results IL-2 produced dose-dependent analgesic effect. Both 5.0 × 106 u/kg and 2.5 ×10^6 u/kg of IL-2 significantly increased the 50% paw withdrawal threshold （P〈0.01） and decreased the paw lifting times in 5 min （P〈0.05） in the neuropathic pain model mice. Their effect lasted for 30 rain and 15 min respectively. 1.0 〈10^6 u/kg of IL-2 did not show significant analgesic effect. The analgesic effect induced by IL-2 was not reversed by pretreatment with naloxone. Conclusion IL-2 produces analgesia in the neuropathic pain model mice, and its al.algesic mechanisms are mediated by other multiple ways or molecules besides opioid receptors.