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Elevated H 2 O 2 levels in trinitrobenzene sulfate‐induced colitis rats contributes to visceral hyperalgesia through interaction with the transient receptor potential ankyrin 1 cation channel
Author(s) -
Kogure Yoko,
Wang Shenglan,
Tanaka Kohichi,
Hao Yongbiao,
Yamamoto Satoshi,
Nishiyama Nobuyoshi,
Noguchi Koichi,
Dai Yi
Publication year - 2016
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.13226
Subject(s) - transient receptor potential channel , hyperalgesia , saline , colitis , pharmacology , medicine , inflammatory bowel disease , visceral pain , inflammation , nociception , chemistry , antagonist , anesthesia , endocrinology , receptor , disease
Background and Aim: Inflammatory bowel disease is associated with chronic abdominal pain. Transient receptor potential ankyrin 1 (TRPA1) is a well‐known pain sensor expressed in primary sensory neurons. Recent studies indicate that reactive oxygen species such as hydrogen peroxide (H 2 O 2 ) may activate TRPA1. Methods: Colonic inflammation was induced by intra‐colonic administration of trinitrobenzene sulfate (TNBS) in adult male Sprague–Dawley rats. Visceromotor response (VMR) to colorectal distention (CRD) was recorded to evaluate the visceral hyperalgesia. Rats were sacrificed 1 day after treatment with saline or TNBS; colonic tissues from the inflamed region were removed and then processed to assess the H 2 O 2 content. H 2 O 2 scavenger N‐acetyl‐ l ‐cysteine or a TRPA1 antagonist, HC‐030031, was intravenously administrated to the TNBS‐treated rats or saline‐treated rats. In a parallel experiment, intra‐colonic H 2 O 2 ‐induced visceral hyperalgesia in naïve rats and the effect of intravenous HC‐030031 were measured based on the VMR to CRD. Results: Trinitrobenzene sulfate treatment resulted in significant increase in VMR to CRD at day 1. The H 2 O 2 content in the inflamed region of the colon in TNBS‐treated rats was significantly higher than that of saline‐treated rats. N‐acetyl‐ l ‐cysteine or HC‐030031 significantly suppressed the enhanced VMR in TNBS‐treated rats while saline‐treated rats remained unaffected. Moreover, blockade of TRPA1 activation by HC‐030031 significantly reversed the exogenous H 2 O 2 ‐induced visceral hyperalgesia. Conclusion: These results suggest that H 2 O 2 content of the colonic tissue is increased in the early stage of TNBS‐induced colitis. The increased H 2 O 2 content may contribute to the visceral hyperalgesia by activating TRPA1.