Effect of NGF and anti-NGF on neuropathic pain in rats following chronic constriction injury of the sciatic nerve

The systemic administration of anti-nerve growth factor (NGF) antibodies ca n prevent local sensory hypersensitivity and block nociceptive fibers from sprouting into denervated adult rat skin. However, in the case of chronic c onstriction injury (CCI) in a rat, there is evidence that NGF reverses some effects of axotomy and alleviates thermal hyperalgesia. It is with this in mind that we investigated the influence of local anti-NGF and NGF on neuro pathic pain and collateral sprouting caused by CCI. In our study, we looked at the effects to the ligated nerves after 30 consecutive days of local in jections of anti-NGF and NGF. A high-dose of anti-NGF (1800 ng) was found t o eradicate heat and cold hyperalgesia during postoperative days 16-28 and from days 8 to 34 after CCI, respectively. Our results show that a low-dose anti-NGF (18 ng) only mildly alleviates heat hyperalgesia but not cold hyp eralgesia. There is evidence that a rebound phenomenon occurs for a short p eriod of time after the anti-NGF injections cease. Results show that anti-N GF injections, whether in a high or low dose, significantly reduces the sev erity of autotomy or prevents the spread of collateral sprouting from the s aphenous nerve into the sciatic innervation territory, In contrast, when a NGF (0.75 ng/g body weight) was applied to the ligated nerve immediately af ter the ligation, heat and cold hyperalgesia were eradicated during postope rative days 4-68 and from days 4 to 28, respectively. The results show that the effect of anti-NGF is delayed at the onset, is short in duration, and is dependent on the dosage. However, anti-NGF but not NGF blocked collatera l sprouting and decreased the severity of autotomy, suggesting that anti-NG F may be a better potential alternative analgesic for the treatment of neur opathic pain in humans. The different initiation times to abolish thermal h yperalgesia by anti-NGF (delayed onset) and NGF (early onset) suggests that alterations in neurotrophic factors contribute to the development of behav ioral hyperalgesia via a complex mechanism in CCI rats. (C) 1999 Internatio nal Association for the Study of Pain. Published by Elsevier Science B.V.