Abolishment of TNBS-induced visceral hypersensitivity in mast cell deficient rats.
Mucosal mast cells are implicated in visceral hypersensitivity associated with irritable bowel syndrome (IBS). In this study, we investigated the role of mast cells in the development of visceral hypersensitivity by using mast cell deficient (Ws/Ws) rats and their control (W+/W+). In W+/W+ rats, an injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into the proximal colon produced a significant decrease in pain threshold of the distal colon. Severe mucosal necrosis and inflammatory cell infiltration with concomitant increase in tissue myeloperoxidase activity were observed in the proximal colon that was directly insulted by TNBS, whereas neither necrosis nor increased myeloperoxidase activity occurred in the distal colon, indicating that TNBS-induced hypersensitivity is not caused by the local tissue damage or inflammation in the region of the gut where distention stimuli were applied. On the other hand, TNBS failed to elicit visceral hypersensitivity in Ws/Ws rats. This finding indicates that mast cells are essential for development of TNBS-induced visceral hypersensitivity in rats. Since the severity of TNBS-induced proximal colon injury and MPO activity was not affected by mast cell deficiency, it is unlikely that abolishment of visceral hypersensitivity in mast cell deficient rats was a result of altered development of the primary injury in the proximal colon. There was no difference between sham-operated Ws/Ws and W+/W+ rats in colonic pain threshold to distention stimuli, indicating that mast cells play no modulatory roles in normal colonic nociception. The present results support the view that mucosal mast cells play key roles in the pathogenesis of IBS.
Ohashi
Katsuyo
K
Discovery Research, Pfizer Global Research and Development, Nagoya Laboratories, 5-2, Taketoyo, Chita-gun, Aichi 470-2393, Japan.
Sato
Yasushi
Y
Kawai
Mitsuhisa
M
Kurebayashi
Yoichi
Y
D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000201:enzymology; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000139:chemically induced / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D009336:Necrosis / Q000139:chemically induced; D017288:Pain Threshold / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology*
D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase