An increase in spinal cord noradrenaline is a major contributor to the antihyperalgesic effect of antidepressants after peripheral nerve injury in the rat
An increase in spinal cord noradrenaline is a major contributor to the antihyperalgesic effect of antidepressants after peripheral nerve injury in the rat
复制标题
DOI：
10.1016/j.pain.2012.01.029
复制
发表时间：
2012-05-01
期刊：
影响因子：
7.4
通讯作者：
Saito, Shigeru
中科院分区：
文献类型：
--
作者：
Nakajima, Kunie;Obata, Hideaki;Saito, Shigeru
抗抑郁药通常用于治疗神经性疼痛。临床研究表明，5-羟色胺（5-HT）和去甲肾上腺素（NA）再摄取抑制剂（SNRIs）对神经病理性疼痛的疗效大于选择性5-HT再摄取抑制剂（SSRIs）。在本研究中，我们确定了米那普仑，SNRI，与帕罗西汀，SSRI和马普替林，选择性NA再摄取抑制剂，使用大鼠模型的神经性疼痛的抗痛觉过敏作用的疗效和机制。雄性Sprague-Dawley大鼠进行脊神经结扎（SNL），并测量对爪压力的缩回阈值。腹腔注射米那普仑（3-30 mg/kg）产生剂量依赖性的抗痛觉过敏作用。鞘内注射α 2-肾上腺素能受体拮抗剂咪唑克生（30 μ g）可逆转该作用，但各种5-HT受体拮抗剂不能逆转该作用。帕罗西汀仅在最高试验剂量（10 mg/kg）下产生抗痛觉过敏作用。鞘内注射咪唑克生和昂丹司琼（30 μ g）（一种5-HT 3受体拮抗剂）可逆转这种作用。马普替林产生抗痛觉过敏作用（10和30 mg/kg），鞘内咪唑克生可逆转该作用。在微透析研究中，注射米那普仑或帕罗西汀后脊髓背角NA和5-HT浓度增加，马普替林后仅NA增加。此外，SNL大鼠脊髓NA含量高于正常动物。这些结果表明，增加NA在脊髓中起着重要的作用，不仅NA再摄取抑制剂，但SSRIs的抗痛觉过敏作用。(C)2012年国际疼痛研究协会。由Elsevier B出版。V.保留所有权利。
Antidepressants are often used for the treatment of neuropathic pain. Clinical studies suggest that the efficacy of serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors (SNRIs) for neuropathic pain is greater than that of selective 5-HT reuptake inhibitors (SSRIs). In the present study, we determined the efficacy and mechanisms involved in the antihyperalgesic effects of milnacipran, an SNRI, compared with paroxetine, an SSRI, and maprotiline, a selective NA reuptake inhibitor, using a rat model of neuropathic pain. Male Sprague-Dawley rats underwent spinal nerve ligation (SNL), and the withdrawal threshold to paw pressure was measured. Intraperitoneal injection of milnacipran (3-30 mg/kg) produced a dose-dependent antihyperalgesic effect. The effect was reversed by intrathecal injection of the a2-adrenoceptor antagonist idazoxan (30 mu g), but not by various 5-HT receptor antagonists. Paroxetine produced an antihyperalgesic effect only at the highest dose tested (10 mg/kg). This effect was reversed by intrathecal injection of both idazoxan and ondansetron (30 mu g), a 5-HT3 receptor antagonist. Maprotiline produced an antihyperalgesic effect (10 and 30 mg/kg), and the effect was reversed by intrathecal idazoxan. In microdialysis studies, NA and 5-HT concentrations in the spinal dorsal horn were increased after injection of either milnacipran or paroxetine, and only NA was increased after maprotiline. Furthermore, the NA content in the spinal cord of SNL rats was greater than that in normal animals. These findings suggest that an increase in NA in the spinal cord plays an important role in the antihyperalgesic effects of not only NA reuptake inhibitors but also SSRIs. (C) 2012 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.