Ren K, Thomas D A, Dubner R
Neurobiology and Anesthesiology Branch, NIDR, NIH, Bethesda, MD 20892-4410, USA.
Brain Res. 1995 Nov 20;699(2):286-92. doi: 10.1016/0006-8993(95)00920-l.
Nerve growth factor (NGF) reverses some effects of axotomy and prevents toxic neuropathy in adult rodents. We tested the effect of NGF on behavioral hyperalgesia resulting from a chronic constriction injury (CCI) of the sciatic nerve in the rat [5]. CCI rats exhibit thermal hyperalgesia as demonstrated by a reduction of paw withdrawal latency to a noxious thermal stimulus applied to the paw on the side of injury. The mechanical sensitivity of the ipsilateral hindpaw, assessed with von Frey filaments, was also significantly increased. There were no significant changes in nociceptive thresholds on the contralateral side. When NGF was infused directly on the ligated nerve via an osmotic pump (0.5 microgram/microliter/h for 7 days) immediately after the ligation, thermal hyperalgesia was abolished from postoperative days 5 up to at least two weeks. The CCI-induced decrease in mechanical threshold was also abolished by NGF. However, NGF had only a minor effect on the abnormally long response duration, a second measure of mechanical sensitivity, to the mechanical stimulus. Delayed infusion of NGF four days after the ligation failed to block hyperalgesia. Infusion of NGF on the sciatic nerve of rats that had no CCI had no significant effect on paw withdrawal latency. Infusion of anti-NGF antiserum did not enhance hyperalgesia in CCI rats. These results suggest that alterations in neurotrophic factor(s) contribute to the development of behavioral hyperalgesia in an animal model of neuropathy and that NGF may have therapeutic value in the treatment of neuropathic pain in humans.
神经生长因子（NGF）可逆转轴突切断术的某些效应，并预防成年啮齿动物的中毒性神经病变。我们测试了NGF对大鼠坐骨神经慢性压迫性损伤（CCI）所致行为性痛觉过敏的影响[5]。如对损伤侧爪施加有害热刺激时爪退缩潜伏期缩短所示，CCI大鼠表现出热痛觉过敏。用von Frey细丝评估的同侧后爪机械敏感性也显著增加。对侧的伤害性感受阈值无显著变化。在结扎后立即通过渗透泵将NGF直接注入结扎神经（0.5微克/微升/小时，持续7天），从术后第5天直至至少两周，热痛觉过敏均被消除。NGF也消除了CCI诱导的机械阈值降低。然而，NGF对机械刺激的异常长反应持续时间（机械敏感性的另一种测量指标）仅有轻微影响。结扎后4天延迟注入NGF未能阻断痛觉过敏。将NGF注入未发生CCI的大鼠坐骨神经对爪退缩潜伏期无显著影响。注入抗NGF抗血清并未增强CCI大鼠的痛觉过敏。这些结果表明，神经营养因子的改变促成了神经病变动物模型中行为性痛觉过敏的发展，并且NGF可能对治疗人类神经性疼痛具有治疗价值。
