Department of Psychiatry, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki city, Miyazaki 889-1692, Japan.
Division of Anatomy and Cell Biology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyagino-ku, Sendai 983-8536, Japan.
Eur J Pharmacol. 2019 May 5;850:118-125. doi: 10.1016/j.ejphar.2019.02.013. Epub 2019 Feb 12.
The contribution of serotonin and noradrenaline to the modulation of pruriceptive processing was evaluated by administrating antidepressants or noradrenaline reuptake inhibitors. The pretreatment with milnacipran, a serotonin and noradrenaline reuptake inhibitor, and mirtazapine, a noradrenergic and specific serotonergic antidepressant, attenuated the induction of scratching behavior by chloroquine, a representative pruritogen, indicating the involvement of serotonin and/or noradrenaline in the modulation of pruriceptive processing. By contrast, the single administration of noradrenaline reuptake inhibitor such as atomoxetine and nisoxetine or serotonin reuptake inhibitor such as fluvoxamine and escitalopram had little effect on chloroquine-induced scratching, whereas the induction of scratching behavior by chloroquine was significantly ameliorated by co-administration of serotonin reuptake inhibitors and noradrenaline reuptake inhibitors. These results indicate that the simultaneous increases of serotonin and noradrenaline elicit the attenuating effect on pruriceptive processing induced by acute itch, and may also play a crucial role in the descending itch inhibitory system.
通过给予抗抑郁药或去甲肾上腺素再摄取抑制剂来评估 5-羟色胺和去甲肾上腺素对瘙痒处理的调制作用。米那普仑，一种 5-羟色胺和去甲肾上腺素再摄取抑制剂，和米氮平，一种去甲肾上腺素能和特异性 5-羟色胺能抗抑郁药的预处理，减弱了氯喹（一种代表性的瘙痒原）诱导的搔抓行为的发生，表明 5-羟色胺和/或去甲肾上腺素参与了瘙痒处理的调制。相比之下，单给予去甲肾上腺素再摄取抑制剂如阿托西汀和奈西汀或 5-羟色胺再摄取抑制剂如氟伏沙明和依地普仑对氯喹诱导的搔抓几乎没有影响，而氯喹诱导的搔抓行为通过同时给予 5-羟色胺再摄取抑制剂和去甲肾上腺素再摄取抑制剂显著改善。这些结果表明，5-羟色胺和去甲肾上腺素的同时增加对急性瘙痒引起的瘙痒处理产生减弱作用，并且可能在下行瘙痒抑制系统中也发挥关键作用。
