5-HT2A receptor subtype in the peripheral branch of sensory fibers is involved in the potentiation of inflammatory pain in rats.
One of the major serotonin (5-HT) receptor subtypes expressed in the rat dorsal root ganglion (DRG) neurons is the 5-HT2A receptor. We have previously shown that 5-HT2A receptors in the peripheral sensory terminals are responsible for 5-HT-induced pain and hyperalgesia. In the present study, we characterized neurons expressing 5-HT2A receptors in the rat DRG neurons by means of in situ hybridization, immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and behavioral tests. In situ hybridization on consecutive sections revealed that 5-HT2A receptor mRNA is colocalized with calcitonin-gene related peptide (CGRP) mRNA (100/104; 96.2%) but not with c-Ret mRNA (1/115; 0.9%). Signals for 5-HT2A receptor mRNA were found in 9.4 +/- 2.2% of normal DRG (L5) neurons, most of which were small to medium in size. Four days of complete Freund's adjuvant-induced inflammation of the hindpaw doubled the incidence of 5-HT2A receptor mRNA-expressing neurons to 19.3 +/- 2.8%. The level of 5-HT2A receptor mRNA in DRGs of normal and various pathological conditions was then determined by RT-PCR. The level was up-regulated by peripheral inflammation, but not by axotomy or chronic constriction of the peripheral nerve. Systemic administration of 5-HT2A receptor antagonist (Sarpogrelate HCI) produced analgesic effects on thermal hyperalgesia caused by peripheral inflammation, but failed to attenuate thermal hyperalgesia in chronic constriction injury model. These findings suggest that 5-HT2A receptors are mainly expressed in CGRP-synthesizing small DRG neurons and may be involved in the potentiation of inflammatory pain in the periphery.
Okamoto
Keiichiro
K
Department of Anatomy and Neurobiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama City 641-8509, Japan.
Imbe
Hiroki
H
Morikawa
Yoshihiro
Y
Itoh
Masayuki
M
Sekimoto
Masashi
M
Nemoto
Kiyomitsu
K
Senba
Emiko
E
D000818:Animals; D001522:Behavior, Animal; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics; D002908:Chronic Disease; D004195:Disease Models, Animal; D005620:Freund's Adjuvant / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D006614:Hindlimb; D008297:Male; D009412:Nerve Fibers / Q000737:chemistry / Q000502:physiology; D009437:Neuralgia / Q000503:physiopathology*; D020078:Neurogenic Inflammation / Q000503:physiopathology*; D009475:Neurons, Afferent / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D017288:Pain Threshold / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012702:Serotonin Antagonists / Q000494:pharmacology; D013386:Succinates / Q000494:pharmacology
D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013386:Succinates; C064294:sarpogrelate; D005620:Freund's Adjuvant; D015740:Calcitonin Gene-Related Peptide