title: Serotonin Receptor 2B Mediates Mechanical Hyperalgesia by Regulating Transient Receptor Potential Vanilloid 1.
abstract: Serotonin [5-hydroxytryptamine (5-HT)], an inflammatory mediator, contributes to inflammatory pain. The presence of multiple 5-HT subtype receptors on peripheral and central nociceptors complicates the role of 5-HT in pain. Previously, we found that 5-HT2B/2C antagonist could block 5-HT-induced mechanical hyperalgesia. However, the types of neurons or circuits underlying this effect remained unsolved. Here, we demonstrate that the Gq/11-phospholipase Cβ-protein kinase Cε (PKCε) pathway mediated by 5-HT2B is involved in 5-HT-induced mechanical hyperalgesia in mice. Administration of a transient receptor potential vanilloid 1 (TRPV1) antagonist inhibited the 5-HT-induced mechanical hyperalgesia. 5-HT injection enhanced 5-HT- and capsaicin-evoked calcium signals specifically in isolectin B4 (IB4)-negative neurons; signals were inhibited by a 5-HT2B/2C antagonist and PKCε blocker. Thus, 5-HT2B mediates 5-HT-induced mechanical hyperalgesia by regulating TRPV1 function.
authors.affiliation: Department of Life Sciences, National Central University, Jhongda Road 300, Jhongli, 32054, Taiwan, Republic of China.
authors.forename: Yeu-Shiuan
authors.initials: YS
authors.lastname: Su
authors.affiliation: Department of Life Sciences, National Central University, Jhongda Road 300, Jhongli, 32054, Taiwan, Republic of China.
authors.forename: Yuan-Yi
authors.initials: YY
authors.lastname: Chiu
authors.affiliation: Department of Life Sciences, National Central University, Jhongda Road 300, Jhongli, 32054, Taiwan, Republic of China.
authors.forename: Shih-Yuan
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Life Sciences, National Central University, Jhongda Road 300, Jhongli, 32054, Taiwan, Republic of China. weihsin@cc.ncu.edu.tw.|Institute of Systems Biology and Bioinformatics, National Central University, Jhongli, Taiwan, Republic of China. weihsin@cc.ncu.edu.tw.|Center for Biotechnology and Biomedical Engineering, National Central University, Jhongli, Taiwan, Republic of China. weihsin@cc.ncu.edu.tw.
authors.forename: Wei-Hsin
authors.initials: WH
authors.lastname: Sun
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D006930:Hyperalgesia / Q000378:metabolism*; D037102:Lectins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D054799:Phospholipase C beta / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000378:metabolism; D044403:Receptor, Serotonin, 5-HT2B / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D037102:Lectins; D044403:Receptor, Serotonin, 5-HT2B; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D012701:Serotonin; D051744:Protein Kinase C-epsilon; D054799:Phospholipase C beta; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
keywords: 5-HT2B; Mechanical hyperalgesia; Protein kinase Cε; Serotonin; Transient receptor potential vanilloid 1