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Peripheral and spinal 5-HT receptors participate in cholestatic itch and antinociception induced by bile duct ligation in rats

Although 5-HT has been implicated in cholestatic itch and antinociception, two common phenomena in patients with cholestatic disease, the roles of 5-HT receptor subtypes are unclear. Herein, we investigated the roles of 5-HT receptors in itch and antinociception associated with cholestasis, which wa...

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Detalles Bibliográficos
Autores principales: Tian, Bin, Wang, Xue-Long, Huang, Ya, Chen, Li-Hua, Cheng, Ruo-Xiao, Zhou, Feng-Ming, Guo, Ran, Li, Jun-Cheng, Liu, Tong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099756/
https://www.ncbi.nlm.nih.gov/pubmed/27824106
http://dx.doi.org/10.1038/srep36286
Descripción
Sumario:Although 5-HT has been implicated in cholestatic itch and antinociception, two common phenomena in patients with cholestatic disease, the roles of 5-HT receptor subtypes are unclear. Herein, we investigated the roles of 5-HT receptors in itch and antinociception associated with cholestasis, which was induced by common bile duct ligation (BDL) in rats. 5-HT-induced enhanced scratching and antinociception to mechanical and heat stimuli were demonstrated in BDL rats. 5-HT level in the skin and spinal cord was significantly increased in BDL rats. Quantitative RT-PCR analysis showed 5-HT(1B), 5-HT(1D), 5-HT(2A), 5-HT(3A), 5-HT(5B), 5-HT(6), and 5-HT(7) were up-regulated in peripheral nervous system and 5-HT(1A), 5-HT(1F), 5-HT(2B), and 5-HT(3A) were down-regulated in the spinal cord of BDL rats. Intradermal 5-HT(2), 5-HT(3), and 5-HT(7) receptor agonists induced scratching in BDL rats, whereas 5-HT(3) agonist did not induce scratching in sham rats. 5-HT(1A), 5-HT(2), 5-HT(3), and 5-HT(7) agonists or antagonists suppressed itch in BDL rats. 5-HT(1A) agonist attenuated, but 5-HT(1A) antagonist enhanced antinociception in BDL rats. 5-HT(2) and 5-HT(3) agonists or antagonists attenuated antinociception in BDL rats. Our data suggested peripheral and central 5-HT system dynamically participated in itch and antinociception under cholestasis condition and targeting 5-HT receptors may be an effective treatment for cholestatic itch.