Caffeine blockade of the thermal antihyperalgesic effect of acute amitriptyline in a rat model of neuropathic pain
Caffeine blockade of the thermal antihyperalgesic effect of acute amitriptyline in a rat model of neuropathic pain
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DOI：
10.1016/s0014-2999(00)00336-8
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发表时间：
2000-07-07
影响因子：
5
通讯作者：
Sawynok, J
中科院分区：
文献类型：
--
作者：
Esser, MJ;Sawynok, J
在本研究中，我们试图确定是否管理的咖啡因，一种非选择性腺苷受体拮抗剂，会影响热抗痛觉过敏的急性阿米替林在大鼠模型的神经性疼痛的疗效。通过单侧紧密结扎第五和第六腰脊神经使大鼠神经病变，并使用聚焦光束测试热痛觉过敏。与阿米替林同时全身给予咖啡因（1.5-7.5 mg/kg），阻断了10 mg/kg阿米替林的热抗痛觉过敏作用。在3.75 mg/kg（100%阻滞）剂量下观察到咖啡因产生的最大程度阻滞，该剂量没有可观察到的内在效应。阿米替林（60 μ g）的脊髓给药表现出轻度的抗痛觉过敏作用，不受鞘内咖啡因（100 μ g）预处理的影响。将阿米替林外周给药至神经性爪（在短暂麻醉下）在30和100 nmol下均产生抗痛觉过敏作用，在100 nmol下观察到更大的作用。咖啡因（1500 nmol）的共同管理部分拮抗两种剂量的阿米替林的影响。这项研究的结果表明，在这个模型中，急性阿米替林的热抗痛觉过敏作用可能涉及增强内源性腺苷紧张。鉴于咖啡因的广泛消费，这种参与是重要的，咖啡因可能潜在地减少阿米替林在治疗神经性疼痛中的益处。(C)2000爱思唯尔科技有限公司。保留所有权利。
In the present study, we sought to determine whether administration of caffeine, a non-selective adenosine receptor antagonist, would affect the thermal antihyperalgesic efficacy of acute amitriptyline in a rat model of neuropathic pain. Rats were rendered neuropathic by unilateral tight ligation of the fifth and sixth lumbar spinal nerves, and tested for thermal hyperalgesia using a focused beam of light. Systemic administration of caffeine (1.5-7.5 mg/kg), at the same time as amitriptyline, blocked the thermal antihyperalgesic effect of 10 mg/kg amitriptyline. The greatest degree of block exerted by caffeine was observed with 3.75 mg/kg (100% block), a dose that had no observable intrinsic effect. Spinal administration of amitriptyline (60 mu g) exhibited a mild antihyperalgesic effect that was unaffected by pretreatment with intrathecal caffeine (100 mu g). Peripheral administration of amitriptyline into the neuropathic paw (under brief anesthesia) produced an antihyperalgesic effect at both 30 and 100 nmol, with a greater effect being observed at 100 nmol. Coadministration of caffeine (1500 nmol) partially antagonized the effects of both doses of amitriptyline. The results of this study suggest that the thermal antihyperalgesic effect of acute amitriptyline in this model may involve enhancement of an endogenous adenosine tone. This involvement is important in light of the widespread consumption of caffeine, which may potentially act to reduce the benefits of amitriptyline in the treatment of neuropathic pain. (C) 2000 Elsevier Science B.V. All rights reserved.