5-HT2A receptor subtype in the peripheral branch of sensory fibers is involved in the potentiation of inflammatory pain in rats

Keiichiro Okamoto, Hiroki Imbe, Yoshihiro Morikawa, Masayuki Itoh, Masashi Sekimoto, Kiyomitsu Nemoto, Emiko Senba

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)133-143
Number of pages11
JournalPain
Volume99
Issue number1-2
DOIs
StatePublished - Sep 1 2002

Keywords

  • Calcitonin-gene related peptide
  • Dorsal root ganglion
  • Inflammatory pain
  • Nerve growth factor
  • Serotonin
  • Serotonin 2A receptor

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