己酮可可碱通过抑制小胶质细胞激活减轻大鼠痛觉超敏和痛觉过敏

Pentoxifylline attenuates hyperalgesia and allodynia in rats with neuropathic pain via inhibiting the activation of spinal cord microglia

目的:观察己酮可可碱腹腔注射对大鼠坐骨神经分支选择性损伤致神经病理性疼痛的作用。方法:切断腓总神经和胫神经保留腓肠神经,制作坐骨神经分支选择性损伤模型。16只雄性SD大鼠从术前1 d起至术后6 d腹腔注射己酮可可碱100 mg.kg-1,qd。观察术前1 d和术后1,3,5,7和14 d大鼠的机械缩足反射阈值(MWT)和热缩足反射持续时间(TWD);并测定不同组别脊髓小胶质细胞标志物OX-42的表达。实验同时设假手术组和坐骨神经分支选择性损伤模型组(n=16)。结果:大鼠坐骨神经选择性切断后1 d起MWT降低、TWD延长,与假手术组比差异有显著性统计学意义(P<0.05);己酮可可碱组MWT增加、TWD缩短,与模型组相比差异有显著性统计学意义(P<0.05);己酮可可碱组部分坐骨神经切断后脊髓OX-42的表达和小胶质细胞阳性细胞数均显著减少。结论:己酮可可碱腹腔注射可抑制坐骨神经分支选择性损伤致脊髓小胶质细胞的激活,减轻痛觉超敏和痛觉过敏。

Objective ： To investigate the effect of intraperitoneal pentoxifylline on neuropathic pain induced by spared nerve injury in the branches of the sciatic nerve in rats. Methods： The spared nerve injury in the branches of the sciatic nerve was induced by completely cutting off left tibial and common peroneal nerves in rats. In 16 male SD rats, 100 mg· kg^-1 pentoxifylline（PTX） was injected intraperitoneally, once a day, from 1 day before nerve transection to 6 days after operation. The mechanical withdrawal threshold （MWT） and thermal withdrawal threshold duration（TWD） were determined at the first day before operation and 1, 3, 5, 7, 14 days after operation. Microglia in the spinal cord were detected by immunofluorescence with OX-42 antibody. Results： Compared to the sham control, MWT decreased and TWD prolonged significantly（P 〈0.05） at 1 , 3, 5, 7, 14 day after the operation for the spared nerve injury. Pentoxifylline significantly attenuated the decreased MWT and prolonged TWD（P 〈0.05） in the rats with spared nerve injury; it also markedly decreased the expression of OX-42 and the number of OX-42-positive microglia （ P 〈 0.05 ）. Conclusion： Pentoxifylline can inhibit the activation of spinal cord microglia after spared nerve injury in the branches of the sciatic nerve in rats, and attenuate hyperalgesia and allodynia.