目的:观察在完全没有神经损伤的情况下,单纯外源性肿瘤坏死因子-α(TNF-α)是否能引起神经病理性疼痛。方法:利用行为学测试的方法,检测坐骨神经周围给予重组大鼠肿瘤坏死因子-α(rrTNF)对大鼠50%机械刺激撤足阈值及热刺激撤足潜伏期的影响。同时在给予rrTNF前后鞘内给予NF-κB抑制剂PDTC,检测大鼠50%机械刺激撤足阈值及热刺激撤足潜伏期的变化。结果:10、100、1000ng/L rrTNF(每天1次,连续2d)可引起大鼠双侧后爪机械刺激和热刺激痛觉过敏,持续20d左右。预先给予PDTC可完全防止rrTNF引起机械痛觉过敏,并可使热刺激撤足潜伏期的下降延迟。疼痛产生以后,再给予PDTC对已经形成的机械痛敏无明显作用,对热痛敏却有短暂的抑制作用。结论:坐骨神经周围给予rrTNF可引起大鼠产生机械痛敏和热痛敏,NF-κB信号转导途径在其中起作用。
AIM: To test the possibility that TNF -α can induce the display of nocieeptive behaviors in rats without any injury. METHODS: The induction of changes in 50% paw withdrawal threshold and paw withdrawal latency by peri - sciatic administration of recombinant rat TNF -α (rrTNF) was determined with the methods of behavioral tests. PDTC (a NF - κB inhibitor) was also intrathecally delivered before or after the administration of rrTNF. RESULTS: We found that peri - sciatic administration of rrTNF at the concentrations of 10, 100, and 1 000 ng/L ( daily for 2 d) induced mechanical allodynia and thermal hyperalgesia in bilateral hindpaws, lasting for around 20 d. Intrathecal administration of PDTC 30 min before each peri - scitic administration of rrTNF completely prevented the decrease in bilateral thresholds, and delayed the decrease of paw withdrawal latencies. In contrast, the same dose of PDTC had no effect on mechanical allodynia when applied intrathecally 6 d after the first administration of rrTNF, while inhibited thermal hyperalgesia for about 7 d. CONCLUSION: Without any nerve injury, perisciatic administration of recombinant rat TNF -α at low doses produces mechanical allodynia and thermal hyperalgesia in bilateral hindpaws. NF-κB pathway may play different roles in mechanical allodynia and thermal hyperalgesia.