title: Systemic administration of 5-HT(2C) receptor agonists attenuates muscular hyperalgesia in reserpine-induced myalgia model.
abstract: Fibromyalgia is a prevalent musculoskeletal disorder characterized by chronic widespread pain that significantly reduces quality of life in patients. Due to the lack of consistently effective treatment, the development of improved therapies for treating fibromyalgia is necessary. As dysfunction of serotonergic analgesic control appears to be involved in the pathophysiology of fibromyalgia, the present study explored the potential of 5-HT(2C) receptor agonists as novel therapies for treating this disease. Three 5-HT(2C) receptor agonists (lorcaserin, vabicaserin and YM348) that have been suggested to be useful in the treatment of several central nervous system diseases, including obesity and schizophrenia, were used. The effect of systemic administration of these agents on the muscular hyperalgesia that develops in the reserpine-induced myalgia (RIM) rat, a putative animal model of fibromyalgia, was investigated. RIM rats exhibited decreased muscle pressure thresholds. Microdialysis experiments showed that the concentration of serotonin (5-HT) in the spinal cord of RIM rats was significantly lower than that of controls. Lorcaserin (0.3-3 mg/kg p.o.), vabicaserin (0.3-3 mg/kg s.c.) and YM348 (0.03-0.3 mg/kg p.o.) recovered the muscle pressure threshold. The effect of lorcaserin was reversed by the pretreatment with SB242084, a 5-HT(2C) receptor antagonist. Our findings demonstrate that 5-HT(2C) receptors play a critical role in muscular hyperalgesia in RIM rats and suggest that 5-HT(2C) receptor agonists have therapeutic potential for treating chronic pain in patients with fibromyalgia although clinical extrapolation remains to be a future challenge.
authors.affiliation: Pharmacology Research Labs, Drug Discovery Research, Astellas Pharma Inc., Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ogino
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Nagakura
authors.forename: Mina
authors.initials: M
authors.lastname: Tsukamoto
authors.forename: Tomonari
authors.initials: T
authors.lastname: Watabiki
authors.forename: Tohru
authors.initials: T
authors.lastname: Ozawa
authors.forename: Tomoya
authors.initials: T
authors.lastname: Oe
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ito
mesh_terms: D000818:Animals; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D008124:Locomotion / Q000187:drug effects; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects*; D012110:Reserpine / Q000008:administration & dosage; D012701:Serotonin / Q000032:analysis; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D013116:Spinal Cord / Q000737:chemistry / Q000187:drug effects
chemical_list: D044405:Receptor, Serotonin, 5-HT2C; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D012110:Reserpine