Antinociception with intrathecal alpha-methyl-5-hydroxytryptamine, a 5-hydroxytryptamine 2A/2C receptor agonist, in two rat models of sustained pain.
Type 2 serotonin (5-hydroxytryptamine [5-HT](2)) receptors in the spinal cord have been reported to mediate antinociception using pain threshold tests, but little is known about the actions of spinal 5-HT(2) receptors in sustained pain. In rats, we examined antinociceptive effects of the intrathecal administration of a 5-HT(2A/2C) receptor agonist, alpha-methyl-5-HT maleate (alpha-m-5-HT), using the formalin test and the chronic constriction injury (CCI) model. An intrathecal catheter was implanted for injection of drugs. In the formalin test, flinches were counted from Minute 1 to 2 and Minute 5 to 6 (Phase 1) and then for 1-min periods at 5-min intervals from 10 to 60 min (Phase 2). In rats with CCI, hind paw withdrawal latency after thermal stimulation was measured. In the formalin test, intrathecal administration of alpha-m-5-HT (1 to 100 microg) dose-dependently suppressed the number of flinches in both Phases 1 and 2. In the CCI model, intrathecally administered alpha-m-5-HT (10 to 100 microg) attenuated thermal hyperalgesia in a dose-dependent manner. These effects were reversed by intrathecal pretreatment with a 5-HT(2A/2C) antagonist, ketanserin (30 microg), or a muscarinic receptor antagonist, atropine (30 microg). These findings suggest that spinal 5-HT(2A/2C) receptors mediate antinociception in inflammatory pain and neuropathic pain, and the muscarinic receptors contribute to this action.


CONCLUSIONS
Activation of spinal 5-hydroxytryptamine(2A/2C) receptors mediate antinociception in rat-sustained pain models such as inflammatory pain and neuropathic pain, and spinal muscarinic receptors are involved in this action.
Sasaki
Masayuki
M
Department of Anesthesiology and Reanimatology, Gunma University School of Medicine, Maebashi, Japan.
Obata
Hideaki
H
Saito
Shigeru
S
Goto
Fumio
F
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D006930:Hyperalgesia / Q000188:drug therapy / Q000523:psychology; D007278:Injections, Spinal; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*
D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D018727:Muscarinic Antagonists; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D005557:Formaldehyde; C042390:alpha-methylserotonin; D012701:Serotonin