Spinal dopaminergic involvement in the antihyperalgesic effect of antidepressants in a rat model of neuropathic pain
Spinal dopaminergic involvement in the antihyperalgesic effect of antidepressants in a rat model of neuropathic pain
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DOI：
10.1016/j.neulet.2017.04.017
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发表时间：
2017-05-10
影响因子：
2.5
通讯作者：
Obata, Hideaki
中科院分区：
文献类型：
--
作者：
Chen, Mi;Hoshino, Hajime;Obata, Hideaki
抗抑郁药如三环类抗抑郁药和血清素去甲肾上腺素再摄取抑制剂是神经性疼痛的一线治疗药物。在这里，我们的目的是确定参与脊髓多巴胺能系统的抗抑郁药的抗痛觉过敏的影响，在大鼠模型的神经病理性疼痛引起的脊神经结扎（SNL）。在吸入麻醉下结扎雄性Sprague-Dawley大鼠的右侧L5脊神经以诱导痛觉过敏。在腹膜内注射阿米替林、度洛沙汀、米那普仑和氟西汀后，通过测量同侧后爪缩回阈值进行行为测试。鞘内注射舒必利可阻断D2样受体。我们还测定了注射抗抑郁药后使用微透析脊髓中多巴胺的浓度。于SNL手术后2、3、4、8周测定正常和SNL大鼠脊髓背角多巴胺含量。腹膜内注射阿米替林、度洛昔单抗、米那普仑和氟西汀（3-30 mg/kg）产生抗痛觉过敏作用，鞘内预注射舒必利（30 μ g）可预防。微透析显示，每种抗抑郁药（10 mg/kg）腹腔注射后，脊髓中的多巴胺水平增加。此外，SNL后2周脊髓组织匀浆中多巴胺含量增加，随后下降。我们的研究结果表明，抗抑郁药对神经病理性疼痛的影响不仅与去甲肾上腺素和5-羟色胺有关，而且与脊髓中多巴胺水平的调节有关。(C)2017爱思唯尔B. V.保留所有权利。
Antidepressants such as tricyclic antidepressants, and serotonin noradrenaline reuptake inhibitors are a first-line treatment for neuropathic pain. Here, we aimed to determine the involvement of the spinal dopaminergic system in the antihyperalgesic effects of antidepressants in a rat model of neuropathic pain induced by spinal nerve ligation (SNL). The right L5 spinal nerve of male Sprague-Dawley rats was ligated under inhalation anesthesia to induce hyperalgesia. Behavioral testing was performed by measuring ipsilateral hindpaw withdrawal thresholds after intraperitoneal injection of amitriptyline, duloxetine, milnacipran, and fluoxetine. D2-like receptors were blocked by intrathecal administration of sulpiride. We also determined the concentrations of dopamine in the spinal cord using microdialysis after injection of antidepressants. The dopamine contents in the spinal dorsal horn were also measured in normal and SNL rats at 2, 3, 4, and 8 weeks after SNL surgery. Intraperitoneal injection of amitriptyline, duloxetine, milnacipran, and fluoxetine (3-30 mg/kg) produced antihyperalgesic effects, and prevented by intrathecal pre-injection of sulpiride (30 mu g). Microdialysis revealed the dopamine levels in the spinal cord were increased after intraperitoneal injection of each antidepressant (10 mg/kg). Furthermore, the dopamine content in homogenized spinal cord tissue were increased at 2 weeks after SNL and then subsequently declined. Our results suggest that the effect of antidepressants against neuropathic pain is related to modulation of not only noradrenalin and serotonin but also dopamine levels in the spinal cord. (C) 2017 Elsevier B.V. All rights reserved.