Kesim Murat, Duman Erdem N, Kadioglu Mine, Yaris Ersin, Kalyoncu Nuri I, Erciyes Nesrin
Department of Pharmacology, Karadeniz Technical University School of Medicine, Trabzon, Turkey.
J Pharmacol Sci. 2005 Jan;97(1):61-6. doi: 10.1254/jphs.fp0040153. Epub 2005 Jan 15.
Serotonin (5-HT) is known to be an important mediator in pain modulation. Some centrally acting agents, like selective serotonin reuptake inhibitors (SSRIs), modulate pain. Activation of the endogenous opioid mechanisms or potentiation of analgesic effect by serotonergic and/or noradrenergic pathways might be involved in antinociception of SSRIs. However, peripheral mechanisms of nociception are not clear. In this study, the antinociceptive effect of paroxetine, its interaction with the opioidergic system and serotonin receptors were tested using the writhing test in mice. Paroxetine (5, 10, 20 mg/kg) induced an antinociceptive effect following i.p. administration in writhing test. For the groups in which the antagonists were tested, the dose of paroxetine that caused a significant and equipotent analgesic effect similar to 0.5 mg/kg morphine was selected. Naloxone significantly antagonized the antinociceptive effects of both paroxetine and morphine in a similar pattern and magnitude. Ketanserin (5-HT(2)-receptor antagonist) or ondansetron (5-HT(3)-receptor antagonist) alone did not alter the nociceptive action of acetic acid. While the antinociceptive effect of paroxetine was highly potentiated by ketanserin, ondansetron reduced that antinociception. In conclusion, our results indicate that the antinociceptive effect of paroxetine mainly depends on central opioidergic and serotonergic mechanisms. Peripheral serotonergic mechanisms/receptors may contribute to this antinociceptive effect, especially by 5-HT(3)-receptor subtypes.
血清素（5-羟色胺，5-HT）是已知的疼痛调节中的重要介质。一些中枢作用药物，如选择性5-羟色胺再摄取抑制剂（SSRIs），可调节疼痛。内源性阿片机制的激活或5-羟色胺能和/或去甲肾上腺素能途径对镇痛作用的增强可能参与了SSRIs的抗伤害感受作用。然而，伤害感受的外周机制尚不清楚。在本研究中，使用小鼠扭体试验检测了帕罗西汀的抗伤害感受作用、其与阿片系统及5-羟色胺受体的相互作用。帕罗西汀（5、10、20mg/kg）腹腔注射后在扭体试验中产生抗伤害感受作用。对于测试拮抗剂的组，选择能产生与0.5mg/kg吗啡相似的显著且等效镇痛作用的帕罗西汀剂量。纳洛酮以相似的模式和程度显著拮抗了帕罗西汀和吗啡的抗伤害感受作用。酮色林（5-HT₂受体拮抗剂）或昂丹司琼（5-HT₃受体拮抗剂）单独使用时不改变乙酸的伤害感受作用。虽然酮色林可高度增强帕罗西汀的抗伤害感受作用，但昂丹司琼减弱了该抗伤害感受作用。总之，我们的结果表明，帕罗西汀的抗伤害感受作用主要依赖于中枢阿片能和5-羟色胺能机制。外周5-羟色胺能机制/受体可能对这种抗伤害感受作用有贡献，尤其是通过5-HT₃受体亚型。
