Antihyperalgesic effects of intrathecal perospirone in a rat model of neuropathic pain
Antihyperalgesic effects of intrathecal perospirone in a rat model of neuropathic pain
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DOI：
10.1016/j.pbb.2020.172964
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发表时间：
2020-08-01
影响因子：
3.6
通讯作者：
Terada, Tadanori
中科院分区：
文献类型：
--
作者：
Haranishi, Yasunori;Hara, Koji;Terada, Tadanori
从脑干到脊髓的下行多巴胺能通路调节疼痛处理的各个方面。脊髓5-羟色胺（5-HT）（1A）和5-HT 2A受体在疼痛调节中起关键作用。Perospirone是一种新型非典型抗精神病药，可作为5-羟色胺（5-HT）（1A）受体激动剂、5-HT 2A受体拮抗剂和多巴胺D-2受体拮抗剂。Lithe知道perospirone对疼痛传递的影响。在这里，我们探讨是否perospirone衰减脊髓神经性疼痛和炎性疼痛。在雄性Sprague-Dawley大鼠中诱导坐骨神经的慢性压迫性损伤。我们评估了鞘内注射哌罗匹隆（10，20，或40 μ g）对机械和冷痛觉过敏的影响，使用电子冯弗雷和冷板测试，分别。用福尔马林WA评估正常大鼠的炎性伤害感受，并采用旋转棒试验评估运动协调。为了确定哌罗匹隆作用的潜在机制，使用电子von Frey WA和冷板试验检查了用5-HT 1A受体拮抗剂WAY-100635、5-HT 2A/2C受体激动剂1-（2，5-二甲氧基-4-碘苯基）-氨基丙烷（DOI）和多巴胺D-2受体激动剂舒马尼罗鞘内预处理对哌罗匹隆作用的影响。哌罗匹隆剂量依赖性地减轻机械和冷痛觉过敏，但不影响脊髓中的炎性伤害感受，并影响运动协调。WAY-100635显著逆转了哌罗匹隆的抗痛觉过敏作用，但DOI和sumanirole均未表现出这种作用。我们的结论是，哌罗匹隆衰减机械和冷痛觉过敏主要通过5-HT 1A受体激活脊髓中，和代理是一个有前途的新的候选神经病理性疼痛缓解。
The descending serotonergic pathway, from the brainstem to spinal cord, modulates various aspects of pain processing. The spinal 5-hydroxytryptamine (5-HT)(1A) and 5-HT2A receptors play pivotal roles in pain modulation. Perospirone is a novel atypical antipsychotic that serves as a 5-hydroxytryptamine (5-HT)(1A) receptor agonist, a 5-HT2A receptor antagonist, and a dopamine D-2 receptor antagonist. Lithe is known about the effect of perospirone on pain transmission. Here, we explored whether perospirone attenuated neuropathic and inflammatory pain in the spinal cord. A chronic constriction injury to the sciatic nerve was induced in male Sprague-Dawley rats. We evaluated the effects of intrathecal administration of perospirone (10, 20, or 40 mu g) on mechanical and cold hyperalgesia using the electronic von Frey and cold plate tests, respectively. Normal rats were assessed in terms of inflammatory nociception using the formalin WA and for motor coordination employing the rotarod test. To define the mechanism underlying the action of perospirone, the effects of intrathecal pretreatment with the 5-HT1A receptor antagonist WAY-100635, the 5-HT2A/2C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-aminopropane (DOI), and the dopamine D-2 receptor agonist sumanirole on perospirone action were examined using the electronic von Frey WA and cold plate test. Perospirone dose-dependently alleviated mechanical and cold hyperalgesia, but not inflammatory nociception in the spinal cord, and affected motor coordination. WAY-100635 reversed the antihyperalgesic action of perospirone significantly, but neither DOI nor sumanirole exhibited such an effect. We conclude that perospirone attenuates mechanical and cold hyperalgesia principally via 5-HT1A receptor activation in the spinal cord, and the agent is a promising novel candidate for neuropathic pain relief.