title: Involvement of serotonin 2A receptors in the analgesic effect of tramadol in mono-arthritic rats.
abstract: The analgesic effects of tramadol are considered to be mediated by both the opioid system and the serotonergic system. This study investigated the involvement of a subtype of serotonin receptors, 5-hydroxytryptamine (5-HT)2A receptor, in the analgesic effect of tramadol. The intraperitoneal (i.p.) injection of tramadol reduced the paw withdrawal latency (PWL) to radiant heat testing in mono-arthritic rats. The antagonistic effect of i.p. ketanserin (a 5-HT2A receptor antagonist) on tramadol analgesia was observed. The expression of the 5-HT2A receptor mRNA in the nucleus of raphe magnus (NRM), ventrolateral periaqueductal gray (vlPAG) and spinal dorsal horn of mono-arthritic rats after a ten-day treatment with tramadol was measured with in situ hybridization. Either single injections or 10 days of tramadol treatment dose-dependently elevated PWL of arthritic rats while ketanserin could partially antagonize the tramadol analgesic effect. Expression of the 5-HT2A receptor mRNA in NRM, ipsilateral vlPAG, and the ipsilateral spinal dorsal horn of arthritic rats was significantly increased after tramadol treatment. These results suggest that 5-HT2A receptors are involved in the analgesic effect of tramadol. This study provides evidence for involvement of 5-HT2A receptors in the tramadol analgesia of inflammatory pain. The increase in this receptor mRNA in the chronic study may contribute to the sustaining effect of tramadol long-term treatments in clinical practice.
authors.affiliation: Department of Integrative Medicine, Institute of Acupuncture Research, Shanghai Medical College of Fudan University, Shanghai 200032, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xie
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Dong
authors.forename: Fei
authors.initials: F
authors.lastname: Ma
authors.forename: William R
authors.initials: WR
authors.lastname: Bauer
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Gen-Cheng
authors.initials: GC
authors.lastname: Wu
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D018771:Arthralgia / Q000188:drug therapy* / Q000209:etiology; D001168:Arthritis / Q000150:complications / Q000188:drug therapy*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014147:Tramadol / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D000701:Analgesics, Opioid; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D012701:Serotonin; D014147:Tramadol; D007650:Ketanserin