5-HT2A receptor subtype is involved in the thermal hyperalgesic mechanism of serotonin in the periphery.
The present study was designed to investigate which subtypes of 5-HT receptors are involved in 5-HT-induced hyperalgesia using behavioral assessment of hyperalgesia. 5-HT and various putative agonists for 5-HT receptor subtypes (5-HT(1A, 2, 3)) were intradermally injected into the rat ipsilateral hindpaw. Paw-withdrawal latency to radiant heat stimulation was examined every 15 min for 2 h. Injection of 5-HT (30 microg) and 5-HT2A receptor agonist (alpha-methyl 5-HT; 0.86 mg/kg) significantly reduced the paw-withdrawal latency. On the other hand, injection of 5-HT3 receptor agonists (2-methyl 5-HT; 0.86 mg/kg, m-CPG; 8 mg/kg) did not produce hyperalgesia. Furthermore, pretreatment with 5-HT2A receptor antagonist (ketanserin), but not with 5-HT3 receptor antagonist (tropisetron), attenuated the behavioral response after the injection of 5-HT. These findings strongly suggest that the 5-HT2A receptor subtype, but not the 5-HT3 subtype, is involved in 5-HT-induced hyperalgesia in acute injury and inflammation in the rat. In situ hybridization histochemistry revealed the presence of 5-HT2 receptor mRNA in a subpopulation of both large and small neurons in the rat dorsal root ganglia.
Department of Anatomy and Neurobiology, Wakayama Medical College, 27 Kyuban-cho, Wakayama 640-8155, Japan.
Atsushi
A
Tokunaga
Misako
M
Saika
Emiko
E
Senba
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology*; D017403:In Situ Hybridization; D008297:Male; D017933:Peripheral Nervous System / Q000503:physiopathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin