Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shandong University Cheeloo Medical College, Shandong, China.
College of Agricultural and Biological Engineering, Heze University, Shandong, China.
Neurogastroenterol Motil. 2019 Jan;31(1):e13471. doi: 10.1111/nmo.13471. Epub 2018 Sep 19.
The effect of hydrogen sulfide (H 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 H S on colonic afferent activity and the underlying mechanism, which was further elucidated in this study.
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.
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 N -Methyl-l-arginine acetate salt (1 mmol/L), the specific nNOS inhibitor NPLA (1 μmol/L), or N-type Ca 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.
H 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 H S in colon.
硫化氢（H2S）对内脏伤害感受的影响尚不清楚。其具有促进伤害感受和抗伤害感受作用的相互矛盾的证据提出了一系列问题，涉及 H2S 对结肠传入活动的影响及其潜在机制，本研究对此进行了进一步阐明。
在体外记录正常雄性 C57BL/6J 小鼠、Cbs 小鼠和 Wistar 大鼠的结肠肠系膜传入神经放电。评估 Cbs 小鼠和 WT 同窝仔鼠的结直肠扩张（CRD）诱导的腹部退缩反射（AWR）。
硫氢化钠（NaHS）显著降低了小鼠的结肠传入自发性放电、对缓激肽的化学敏感性、对斜坡扩张的机械敏感性以及肠腔内压力。使用非特异性 K 通道阻滞剂 TEA（10 mmol/L）来降低 NaHS 对肠平滑肌的舒张作用，并没有阻断 NaHS 对传入神经活动的抑制作用。非特异性 NOS 抑制剂 N-甲基-L-精氨酸乙酸盐（1 mmol/L）、特异性 nNOS 抑制剂 NPLA（1 μmol/L）或 N 型钙通道阻滞剂 ω-芋螺毒素 GVIA（1 μmol/L）预处理，极大地消除了 NaHS（0.5 mmol/L）对结肠传入感觉敏感性的抑制作用。与 WT 小鼠相比，Cbs 小鼠的肠系膜传入对结肠扩张的敏感性增加，对 CRD 的超敏反应增强。腹腔内给予 NaHS（60 μmol/kg）可缓解 Cbs 和 WT 小鼠对 CRD 的痛觉反应。
在小鼠中，H2S 通过 nNOS 依赖性机制下调结肠肠系膜传入感觉敏感性。我们的发现可能为 H2S 在结肠中的抗伤害感受作用提供了一种新的机制。
