Xiaomeng Xu1, Shuang Li1, Yao Shi1, Yan Tang1, Wen Lu2, Ting Han1, Bing Xue1, Jingxin Li1, Chuanyong Liu1,3. 1. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shandong University Cheeloo Medical College, Shandong, China. 2. College of Agricultural and Biological Engineering, Heze University, Shandong, China. 3. Provincial Key Lab of Mental Disorder, School of Basic Medical Sciences, Shandong University Cheeloo Medical College, Shandong, China.
Abstract
BACKGROUND: The effect of hydrogen sulfide (H2 S) on visceral nociception is elusive. The conflicting evidence of its pro- and antinociceptive effects raises a series of questions with respect to the effect of H2 S on colonic afferent activity and the underlying mechanism, which was further elucidated in this study. METHODS: Colonic mesenteric afferent nerve spikes of normal male C57BL/6J mice, Cbs+/- mice, and Wistar rats were recorded in vitro. The abdominal withdrawal reflex (AWR) induced by colorectal distension (CRD) was evaluated in Cbs+/- mice and WT littermates. KEY RESULTS: Sodium hydrosulfide (NaHS) significantly decreased colonic afferent spontaneous discharge, chemosensitivity to bradykinin, mechanosensitivity to ramp distention, and intraluminal pressure in mice. Reducing the relaxant action of NaHS on intestinal smooth muscle using the nonspecific K+ channel blocker TEA (10 mmol/L) did not block the inhibition of NaHS on afferent nerve activity. The inhibitory effects of NaHS (0.5 mmol/L) on colonic afferent sensitivity were largely eliminated by the pretreatment with nonspecific NOS inhibitor NG -Methyl-l-arginine acetate salt (1 mmol/L), the specific nNOS inhibitor NPLA (1 μmol/L), or N-type Ca2+ channel blocker ω-conotoxin GVIA (1 μmol/L). Compared with WT mice, Cbs+/- mice showed increased mesenteric afferent sensitivity to colonic distention and enhanced hyperalgesic response to CRD. Intraperitoneal administration of NaHS (60 μmol/kg) alleviated the nociception response to CRD in both Cbs+/- and WT mice. CONCLUSIONS AND INFERENCES: H2 S downregulates colonic mesenteric afferent sensitivity by a nNOS-dependent mechanism in mice. Our findings may demonstrate a new mechanism for the antinociceptive effect of H2 S in colon.
BACKGROUND: The effect of hydrogen sulfide (H2 S) on visceral nociception is elusive. The conflicting evidence of its pro- and antinociceptive effects raises a series of questions with respect to the effect of H2 S on colonic afferent activity and the underlying mechanism, which was further elucidated in this study. METHODS: Colonic mesenteric afferent nerve spikes of normal male C57BL/6J mice, Cbs+/- mice, and Wistar rats were recorded in vitro. The abdominal withdrawal reflex (AWR) induced by colorectal distension (CRD) was evaluated in Cbs+/- mice and WT littermates. KEY RESULTS:Sodium hydrosulfide (NaHS) significantly decreased colonic afferent spontaneous discharge, chemosensitivity to bradykinin, mechanosensitivity to ramp distention, and intraluminal pressure in mice. Reducing the relaxant action of NaHS on intestinal smooth muscle using the nonspecific K+ channel blocker TEA (10 mmol/L) did not block the inhibition of NaHS on afferent nerve activity. The inhibitory effects of NaHS (0.5 mmol/L) on colonic afferent sensitivity were largely eliminated by the pretreatment with nonspecific NOS inhibitor NG -Methyl-l-arginine acetate salt (1 mmol/L), the specific nNOS inhibitor NPLA (1 μmol/L), or N-type Ca2+ channel blocker ω-conotoxin GVIA (1 μmol/L). Compared with WT mice, Cbs+/- mice showed increased mesenteric afferent sensitivity to colonic distention and enhanced hyperalgesic response to CRD. Intraperitoneal administration of NaHS (60 μmol/kg) alleviated the nociception response to CRD in both Cbs+/- and WT mice. CONCLUSIONS AND INFERENCES: H2 S downregulates colonic mesenteric afferent sensitivity by a nNOS-dependent mechanism in mice. Our findings may demonstrate a new mechanism for the antinociceptive effect of H2 S in colon.
Authors: Elena Lucarini; Laura Micheli; Eleonora Pagnotta; Roberto Matteo; Carmen Parisio; Alessandra Toti; Valentina Ferrara; Clara Ciampi; Alma Martelli; Lara Testai; Vincenzo Calderone; Michele Savino; Mario Russo; Nicola Pecchioni; Carla Ghelardini; Lorenzo Di Cesare Mannelli Journal: Foods Date: 2022-02-17