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-HT_2A 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-HT_2A receptor antagonist, and a dopamine D₂ receptor antagonist. Little 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 μg) 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 test 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-HT_1A receptor antagonist WAY-100635, the 5-HT_2A/2C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-aminopropane (DOI), and the dopamine D₂ receptor agonist sumanirole on perospirone action were examined using the electronic von Frey test 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-HT_1A receptor activation in the spinal cord, and the agent is a promising novel candidate for neuropathic pain relief.

从脑干到脊髓的血清素能递减途径调节着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是一种新型的非典型抗精神病药，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。关于培洛螺酮对疼痛传播的影响知之甚少。在这里，我们探讨了Perospirone是否能减轻脊髓的神经性和炎症性疼痛。雄性Sprague-Dawley大鼠诱发了坐骨神经的慢性收缩损伤。我们分别通过电子von Frey和冷板试验评估鞘内注射Perospirone（10、20或40μg）对机械和冷痛觉过敏的作用。使用福尔马林测试评估正常大鼠的炎性伤害感受，并使用旋转脚踏测试测试其运动协调性。为了确定培洛斯匹隆作用的基本机制，鞘内预处理5-HT _1A受体拮抗剂WAY-100635、5-HT _{2A / 2C的作用}使用电子冯弗雷试验和冷板试验检查了受体激动剂1-（2,5-二甲氧基-4-碘苯基）-氨基丙烷（DOI）和多巴胺D ₂受体激动剂舒马尼洛对全螺环酮作用的作用。Perospirone剂量依赖性地减轻了机械和冷痛觉过敏，但并未减轻脊髓的炎性痛觉，并影响了运动协调。WAY-100635显着逆转了哌洛酮的抗痛觉过敏作用，但DOI和舒马尼洛均未显示出这种作用。我们得出的结论是，Perospirone主要通过脊髓中的5-HT _1A受体激活来减轻机械性和冷痛觉过敏，并且该药物是缓解神经性疼痛的有希望的新型候选药物。