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 can prevent local sensory hypersensitivity and block nociceptive fibers from sprouting into denervated adult rat skin. However, in the case of chronic constriction 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 neuropathic 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 injections of anti-NGF and NGF. A high-dose of anti-NGF (1800 ng) was found to 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 hyperalgesia. There is evidence that a rebound phenomenon occurs for a short period of time after the anti-NGF injections cease. Results show that anti-NGF injections, whether in a high or low dose, significantly reduces the severity of autotomy or prevents the spread of collateral sprouting from the saphenous nerve into the sciatic innervation territory. In contrast, when a NGF (0.75 ng/g body weight) was applied to the ligated nerve immediately after the ligation, heat and cold hyperalgesia were eradicated during postoperative 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 collateral sprouting and decreased the severity of autotomy, suggesting that anti-NGF may be a better potential alternative analgesic for the treatment of neuropathic pain in humans. The different initiation times to abolish thermal hyperalgesia by anti-NGF (delayed onset) and NGF (early onset) suggests that alterations in neurotrophic factors contribute to the development of behavioral hyperalgesia via a complex mechanism in CCI rats. Copyright (C) 1999 International Association for the Study of Pain. Published by Elsevier Science B.V.