Ro L S, Chen S T, Tang L M, Jacobs J M
Second Department of Neurology, Chang Gung Memorial Hospital and Medical College, Chang Gung University, Taipei, Taiwan.
Pain. 1999 Feb;79(2-3):265-74. doi: 10.1016/s0304-3959(98)00164-x.
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.
全身给予抗神经生长因子（NGF）抗体可预防局部感觉过敏，并阻止伤害性纤维向去神经支配的成年大鼠皮肤内芽生。然而，在大鼠慢性压迫性损伤（CCI）的情况下，有证据表明NGF可逆转轴突切断的某些效应并减轻热痛觉过敏。正是基于这一考虑，我们研究了局部给予抗NGF和NGF对CCI所致神经病理性疼痛和侧支芽生的影响。在我们的研究中，我们观察了连续30天局部注射抗NGF和NGF后对结扎神经的影响。发现高剂量抗NGF（1800 ng）分别在术后第16 - 28天和CCI后第8至34天消除热痛觉过敏和冷痛觉过敏。我们的结果表明，低剂量抗NGF（18 ng）仅轻度减轻热痛觉过敏，但不能减轻冷痛觉过敏。有证据表明，抗NGF注射停止后短时间内会出现反弹现象。结果表明，抗NGF注射，无论高剂量还是低剂量，均显著降低自残的严重程度或阻止隐神经侧支芽生扩散至坐骨神经支配区域。相反，在结扎后立即将NGF（0.75 ng/g体重）应用于结扎神经，热痛觉过敏和冷痛觉过敏分别在术后第4 - 68天和第4至28天消除。结果表明，抗NGF的作用起效延迟、持续时间短且依赖于剂量。然而，抗NGF而非NGF可阻止侧支芽生并降低自残的严重程度，则提示抗NGF可能是治疗人类神经病理性疼痛的更好潜在替代镇痛药。抗NGF（起效延迟）和NGF（起效早）消除热痛觉过敏的不同起始时间表明，神经营养因子的改变通过复杂机制在CCI大鼠行为性痛觉过敏的发生中起作用。
