Effect of NGF and anti-NGF on neuropathic pain in rats following chronic constriction injury of the sciatic nerve
Effect of NGF and anti-NGF on neuropathic pain in rats following chronic constriction injury of the sciatic nerve
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DOI：
10.1016/s0304-3959(98)00164-x
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发表时间：
1999-02-01
期刊：
影响因子：
7.4
通讯作者：
Jacobs, JM
中科院分区：
文献类型：
--
作者：
Ro, LS;Chen, ST;Jacobs, JM
抗神经生长因子（NGF）抗体的全身给药可以防止局部感觉超敏反应和阻断伤害性纤维发芽到失神经成年大鼠皮肤。然而，在大鼠慢性压迫性损伤（CCI）的情况下，有证据表明，NGF逆转了轴突切断术的某些作用，并减轻了热痛觉过敏。考虑到这一点，我们研究了局部抗NGF和NGF对CCI引起的神经病理性疼痛和侧支发芽的影响。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。高剂量的抗神经生长因子（1800 ng）被发现消除热和冷痛觉过敏在术后第16-28天和第8天至34天后CCI，分别。我们的研究结果表明，低剂量的抗神经生长因子（18 ng）只轻度减轻热痛觉过敏，但不冷痛觉过敏。有证据表明，在抗NGF注射停止后的短时间内发生反弹现象。结果显示，无论是高剂量还是低剂量的抗NGF注射，都显著降低了自体切断术的严重程度或防止了从隐神经发芽的侧支扩散到坐骨神经支配区域。（0.75ng/g体重）在结扎后立即施加于结扎的神经，分别在术后4-68天和4 - 28天消除热痛觉过敏和冷痛觉过敏。结果表明，抗NGF的作用是在起效时延迟的，持续时间短，并依赖于剂量。然而，抗-NGF而不是NGF阻断侧支发芽并降低自切的严重程度，这表明抗-NGF可能是治疗人类神经病理性疼痛的更好的潜在替代镇痛剂。不同的起始时间，以消除热痛觉过敏的抗神经生长因子（延迟发作）和神经生长因子（早发）表明，神经营养因子的改变有助于通过一个复杂的机制在CCI大鼠的行为痛觉过敏的发展。(C)1999年国际疼痛研究协会。出版社：Elsevier Science B. V.
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. (C) 1999 International Association for the Study of Pain. Published by Elsevier Science B.V.