title: Elevated H2 O2 levels in trinitrobenzene sulfate-induced colitis rats contributes to visceral hyperalgesia through interaction with the transient receptor potential ankyrin 1 cation channel.
abstract: OBJECTIVE
  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 (H2 O2 ) 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 H2 O2 content. H2 O2 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 H2 O2 -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 H2 O2 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 H2 O2 -induced visceral hyperalgesia.
  
  
  CONCLUSIONS
  These results suggest that H2 O2 content of the colonic tissue is increased in the early stage of TNBS-induced colitis. The increased H2 O2 content may contribute to the visceral hyperalgesia by activating TRPA1.
authors.affiliation: Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Hyogo, 6508530, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kogure
authors.affiliation: Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Hyogo, 6508530, Japan.|Traditional Medicine Research Center, Chinese Medicine Confucius Institute, Hyogo College of Medicine, Kobe, Hyogo, 6508530, Japan.
authors.forename: Shenglan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Hyogo, 6508530, Japan.
authors.forename: Koh-Ichi
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Hyogo, 6508530, Japan.
authors.forename: Yongbiao
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Hyogo, 6508530, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Hyogo, 6508530, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Nishiyama
authors.affiliation: Traditional Medicine Research Center, Chinese Medicine Confucius Institute, Hyogo College of Medicine, Kobe, Hyogo, 6508530, Japan.|Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Noguchi
authors.affiliation: Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Hyogo, 6508530, Japan.|Traditional Medicine Research Center, Chinese Medicine Confucius Institute, Hyogo College of Medicine, Kobe, Hyogo, 6508530, Japan.|Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Yi
authors.initials: Y
authors.lastname: Dai
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D000083:Acetanilides / Q000008:administration & dosage; D000111:Acetylcysteine / Q000008:administration & dosage; D061605:Administration, Intravenous; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D003106:Colon / Q000294:innervation / Q000378:metabolism*; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000008:administration & dosage; D006861:Hydrogen Peroxide / Q000008:administration & dosage / Q000378:metabolism*; D006930:Hyperalgesia / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D017288:Pain Threshold; D011687:Purines / Q000008:administration & dosage; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid; D015854:Up-Regulation; D059265:Visceral Pain / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D016166:Free Radical Scavengers; D011687:Purines; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D014302:Trinitrobenzenesulfonic Acid; D006861:Hydrogen Peroxide; D000111:Acetylcysteine
keywords: H2O2; IBD; TNBS; TRPA1; visceral pain