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 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-HT1B, 5-HT1D, 5-HT2A, 5-HT3A, 5-HT5B, 5-HT6, and 5-HT7were up-regulated in peripheral nervous system and 5-HT1A, 5-HT1F, 5-HT2B, and 5-HT3Awere down-regulated in the spinal cord of BDL rats. Intradermal 5-HT2, 5-HT3, and 5-HT7receptor agonists induced scratching in BDL rats, whereas 5-HT3agonist did not induce scratching in sham rats. 5-HT1A, 5-HT2, 5-HT3, and 5-HT7agonists or antagonists suppressed itch in BDL rats. 5-HT1Aagonist attenuated, but 5-HT1Aantagonist enhanced antinociception in BDL rats. 5-HT2and 5-HT3agonists 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.
Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Bin
B
Tian
Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Xue-Long
XL
Wang
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, 215123, China.
Ya
Y
Huang
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, 215123, China.
Li-Hua
LH
Chen
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, 215123, China.
Ruo-Xiao
RX
Cheng
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, 215123, China.
Feng-Ming
FM
Zhou
Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Ran
R
Guo
Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Jun-Cheng
JC
Li
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, 215123, China.
Tong
T
Liu
D000818:Animals; D002779:Cholestasis / Q000150:complications* / Q000209:etiology / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000378:metabolism; D011537:Pruritus / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D013116:Spinal Cord / Q000378:metabolism
D011985:Receptors, Serotonin; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists