title: Chemo-nociceptive signalling from the colon is enhanced by mild colitis and blocked by inhibition of transient receptor potential ankyrin 1 channels.
abstract: OBJECTIVE
  Transient receptor potential ankyrin 1 (TRPA1) channels are expressed by primary afferent neurones and activated by irritant chemicals including allyl isothiocyanate (AITC). Here we investigated whether intracolonic AITC causes afferent input to the spinal cord and whether this response is modified by mild colitis, morphine or a TRPA1 channel blocker.
  
  
  METHODS
  One hour after intracolonic administration of AITC to female mice, afferent signalling was visualized by expression of c-Fos in laminae I-II(o) of the spinal dorsal horn at sacral segment S1. Mild colitis was induced by dextran sulphate sodium (DSS) added to drinking water for 1 week.
  
  
  RESULTS
  Relative to vehicle, AITC (2%) increased expression of c-Fos in the spinal cord. Following induction of mild colitis by DSS (2%), spinal c-Fos responses to AITC, but not vehicle, were augmented by 41%. Colonic inflammation was present (increased myeloperoxidase content and disease activity score), whereas colonic histology, locomotion, feeding and drinking remained unchanged. Morphine (10 mg.kg(-1)) or the TRPA1 channel blocker HC-030031 (300 mg.kg(-1)) inhibited the spinal c-Fos response to AITC, in control and DSS-pretreated animals, whereas the response to intracolonic capsaicin (5%) was blocked by morphine but not HC-030031.
  
  
  CONCLUSIONS
  Activation of colonic TRPA1 channels is signalled to the spinal cord. Mild colitis enhanced this afferent input that, as it is sensitive to morphine, is most likely of a chemonociceptive nature. As several irritant chemicals can be present in chyme, TRPA1 channels may mediate several gastrointestinal pain conditions.
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Mitrovic
authors.forename: Anaid
authors.initials: A
authors.lastname: Shahbazian
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bock
authors.forename: Maria A
authors.initials: MA
authors.lastname: Pabst
authors.forename: Peter
authors.initials: P
authors.lastname: Holzer
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D003092:Colitis / Q000503:physiopathology*; D003106:Colon / Q000378:metabolism*; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D017879:Isothiocyanates / Q000633:toxicity*; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009475:Neurons, Afferent / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D011687:Purines / Q000494:pharmacology; D015398:Signal Transduction; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*
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; D017879:Isothiocyanates; D016760:Proto-Oncogene Proteins c-fos; D011687:Purines; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D009020:Morphine; D016264:Dextran Sulfate; C004471:allyl isothiocyanate; D002211:Capsaicin