Intrathecal nerve growth factor restores opioid effectiveness in an animal model of neuropathic pain
Intrathecal nerve growth factor restores opioid effectiveness in an animal model of neuropathic pain
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DOI：
10.1016/s0028-3908(03)00192-8
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发表时间：
2003-09-01
影响因子：
4.7
通讯作者：
Coderre, TJ
中科院分区：
文献类型：
--
作者：
Cahill, CM;Dray, A;Coderre, TJ
毫无疑问，神经性疼痛的治疗是一个医疗需求基本上未得到满足的领域。可用的镇痛药（例如吗啡）要么对神经性疼痛患者的影响很小，要么由于并发的不良反应而并不总是耐受良好。神经性疼痛的慢性化被认为与背根神经节（DRG）和脊髓中的许多神经化学变化有关，包括神经生长因子（NGF）逆行转运的减少。在这项研究中，我们已经确定了慢性鞘内（i.t.）输注NGF以逆转神经性疼痛症状并恢复吗啡在神经性疼痛动物模型中的有效性。坐骨神经压迫损伤后7天，通过连接到长期植入的i.t.的渗透泵，通过连续输注（125 ng/穆尔/h）将NGF施用到脊髓。导尿管脊髓注射神经生长因子并不影响神经病大鼠触觉异常性疼痛或热（热）痛觉过敏的表达，虽然它显着增加冷水反应的频率在第14天。输注溶媒后，i.t.吗啡（20 μ g）在改变神经病大鼠的躯体感觉阈值方面无效。相比之下，吗啡显著减弱了神经病诱导的热痛觉过敏和冷痛觉过敏，以及触觉异常性疼痛，在神经病大鼠中，长期i. t.神经生长因子此外，我们证明，i.t.在慢性i.t.输注吗啡的动物中，胆囊收缩素（CCK）拮抗剂可增强吗啡诱导的抗伤害性感受。针对NGF的抗体。我们假设，神经生长因子是至关重要的，在维持脊髓的伤害性神经元的神经化学稳态，并补充可能是有益的，在恢复和/或维持阿片类镇痛慢性疼痛条件下造成的创伤性神经损伤。(C)2003爱思唯尔有限公司。保留所有权利。
It is without dispute that the treatment of neuropathic pain is an area of largely unmet medical need. Available analgesics, such as morphine, either have minimal effects in neuropathic pain patients, or are not always well tolerated due to concurrent adverse effects. The chronicity of neuropathic pain is thought to be related to many neurochemical changes in the dorsal root ganglia (DRG) and spinal cord, including a reduction in the retrograde transport of nerve growth factor (NGF). In this study, we have determined the ability of chronic intrathecal (i.t.) infusion of NGF to reverse neuropathic pain symptoms and to restore morphine's effectiveness in an animal model of neuropathic pain. Seven days after sciatic nerve constriction injury, NGF was administered to the spinal cord by continuous infusion (125 ng/mul/h) via osmotic pumps attached to chronically implanted i.t. catheters. Spinal infusion of NGF did not affect the expression of tactile allodynia or thermal (hot) hyperalgesia in neuropathic rats, although it significantly increased cold water responses frequency at day 14. Following infusion of vehicle, i.t. morphine (20 mug) was ineffective in altering somatosensory thresholds in neuropathic rats. In contrast, morphine substantially attenuated the neuropathy-induced warm and cold hyperalgesia, as well as tactile allodynia, in neuropathic rats chronically infused with i.t. NGF. In addition, we demonstrate that i.t. morphine-induced antinociception was augmented by a cholecystokinin (CCK) antagonist in animals chronically infused with i.t. antibodies directed against NGF. We hypothesize that NGF is critical in maintaining neurochemical homeostasis in the spinal cord of nociceptive neurons, and that supplementation may be beneficial in restoring and/or maintaining opioid analgesia in chronic pain conditions resulting from traumatic nerve injury. (C) 2003 Elsevier Ltd. All rights reserved.