Ulcerogenic Action of Indomethacin on Gastric and Small Intestinal Mucosa in C57/BL6/J and TRPV1 Knockout Mice

Abstract

Capsaicin‐sensitive afferent neurons are involved in maintenance of gastrointestinal mucosa integrity. Capsaicin action is mediated through TRPV1 receptors. The aim of the present study was to elucidate the role of these receptors in providing of protective or/and pathological mechanisms under circumstances of indomethacin (IM)‐induced injury in gastric and small intestinal mucosa. We compared vulnerability of gastric and small intestine mucosa to IM action in mice with genetically deleted TRPV1 receptor and C57/BL6/J mice. IM‐induced injury was assessed by macroscopically as well as histologically; the somatic pain sensitivity was estimated by tail flick latency (tail flick test); plasma corticosterone levels and body weight were also monitored. A single IM administration (35 mg/kg, sc) into fasting (24 h) mice caused the formation of gastric erosions 4 h after injection and, then, after refeeding, formation of the small intestine injury which was visible 24, 48, 72 h after the injection. Although IM‐induced gastrointestinal injury was detectable in both of C57/BL6/J and TRPV1 knockout mice, area of gastric damage was greater in C57/BL6/J than in TRPV1 knockout mice, whereas the small intestine injury (48 and 72 h after IM injection), on contrary, prevailed in TRPV1 knockout mice compared to C57/BL6/J mice. TRPV1 knockout mice also showed an increased tail flick latencies and lower plasma corticosterone levels than C57/BL6/J mice. The data suggests that in TRPV1 knockout mice the gastric mucosa is less vulnerable to ulcerogenic IM action compared to C57/BL6/J mice, whereas their small intestinal mucosa, on contrary, is more susceptible to IM ulcerogenic action than in C57/BL6/J mice.Support or Funding InformationThe study was supported by grant of Russian Science Foundation (RSF) N 14‐15‐00790 and grant of RFBR N 16‐04‐01196aThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.