The nociceptive mechanism of 5-hydroxytryptamine released into the peripheral tissue in acute inflammatory pain in rats.
The present study examined the contribution of 5-hydroxytryptamine (5-HT) to acute peripheral inflammatory pain in rats. We used formalin test in this study. After formalin injection into the rat hind paw, biphasic pain-related behavior (phases 1 and 2) was observed. A microdialysis study revealed that 5-HT was released into the formalin injection site in a formalin concentration-dependent manner (1.25-5%), and its peak time was 18min after the injection. Previous studies suggest that peripheral 5-HT2 receptors are involved in inflammatory pain. Therefore, we next examined whether 5-HT2A and 5-HT2C receptors are involved, and from where 5-HT is released in the formalin test. Local pretreatment with a selective 5-HT2A receptor antagonist, ketanserin, and selective 5-HT2C receptor antagonists, RS102221 and SB242084, inhibited the number of flinches in early part of phase 2 (phase 2A) of the formalin test in a dose-dependent manner. Peripheral pretreatment with sodium cromoglycate (cromolyn), a mast cell membrane stabilizer, completely suppressed 5-HT release and inhibited phase 2 responses of the formalin test. These drugs inhibited c-fos expression in the superficial layer of the spinal dorsal horn of segments L4-5 at 2h after formalin injection. These results indicate that 5-HT released into peripheral tissue and its receptors, 5-HT2A as well as 5-HT2C, at the periphery have an important role in pain-related behaviors during acute peripheral inflammation.
Nakajima
Kunie
K
Department of Anesthesiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-Machi, Maebashi, Gunma 371-8511, Japan.
Obata
Hideaki
H
Ito
Naomi
N
Goto
Fumio
F
Saito
Shigeru
S
D000208:Acute Disease; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D004205:Cromolyn Sodium / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb / Q000294:innervation / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology
D018927:Anti-Asthmatic Agents; D016760:Proto-Oncogene Proteins c-fos; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D004205:Cromolyn Sodium