Increased 5-hydroxytryptamine mediates post-inflammatory visceral hypersensitivity via the 5-hydroxytryptamine 3 receptor in rats

Yun Dong Choi, Tae Sik Sung, Hyun Ju Kim, Jun Ho La, Tae Wan Kim, Il Suk Yang

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Visceral hypersensitivity often develops after intestinal inflammation, but the pathogenic mechanism has not been clearly elucidated. We investigated whether this post-inflammatory visceral hypersensitivity is mediated by 5-hydroxytryptamine through activation of the 5-hydroxytryptamine 3 receptor. In male Sprague-Dawley rats recovered from acetic acid-induced colitis, we monitored visceral nociceptive response by scoring the abdominal withdrawal reflex and simultaneously measuring the changes in arterial pulse rate. Seven days after induction of colitis, 52% of the rats showed an increased abdominal withdrawal reflex score and arterial pulse rate changes to colorectal distension, indicating that they had post-inflammatory visceral hypersensitivity. The 5-hydroxytryptamine 3 receptor antagonists, alosetron (20 mg/kg, p.o.) and granisetron (10 μg/kg, s.c.), inhibited post-inflammatory visceral hypersensitivity. Administration of a 5-hydroxytryptamine precursor, 5-hydroxytryptophan; 10 mg/kg, s.c.), induced visceral hypersensitivity in naïve rats, which was antagonized by granisetron. Increase in 5-hydroxytryptamine immunoreactive cells in colonic mucosal layer was found both in the rats with post-inflammatory visceral hypersensitivity and in the 5-hydroxytryptophan-treated rats. These results suggest that increased 5-hydroxytryptamine in colonic mucosa mediates post-inflammatory visceral hypersensitivity through activation of the 5-hydroxytryptamine 3 receptor.

Original languageEnglish (US)
Pages (from-to)2909-2916
Number of pages8
JournalDigestive Diseases and Sciences
Volume53
Issue number11
DOIs
StatePublished - Nov 2008

Keywords

  • 5-Hydroxytryptamine
  • Colorectal distension
  • Intestinal inflammation
  • Post-inflammatory visceral hypersensitivity

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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