Study For The Pathophysiology Of Visceral Hypersensitivity And Disorder Of Gastrointestinal Motility

Objective:To investigate the effect of different concentration of a new simplified herbal combination product STW-5-NII on intestinal afferent nerve discharge after different mechanical and chemical stimuli.Methods:24 male Wister Rats were divided into four groups.STW-5-NII at a concentration of 100%,50%,25%or vehicle were administered orally in rats after anesthetized.The extracellular multi-unit mesenteric afferent nerve recordings were obtained in the proximal jejunum.Afferent discharge to 5-Hydroxytryptamine(5-HT) (5,10,20 and 40μg kg^-1,i.v.),bradykinin(BK)(15,30 and 60μg kg^-1i.v.)and luminal distension(0cmH₂O -60cmH₂O)were recorded and analyzed.Results:Afferent nerve discharge was increased after different dose of 5-HT and BK. Afferent nerve sensitivity to bradykinin but not to 5-HT was significantly different depending on the dose of pretreatment with STW-5-NII.A pressure-dependent increase in afferent nerve discharge was observed during intraluminal distension that was not significant different following pretreatment with any concentraction of STW-5-NII.Conclusions:The herbal preparation STW-5-NII desensitized intestinal afferents selectively to systemic bradykinin.This new preparation might be helpful for patients suffering from disorders associated with visceral hypersensitivity. Objective To investigate the effects of CB agonist and antagonist on the afferent nerve discharge in the intestinal experimental hypersensitivity and the intestinal myoelectric activity in rats.Methods Experiment in vitro:Wistar rats were anesthetized and ileal segments removed with the mesenteric arcade attached.The segments were perfused with Krebs' buffer(37℃)which was either supplemented with the CB-1 receptor agonist WIN 55,212-2(10^-5mold),or the CB-1 receptor antagonist SR 141716A(10^-5mol/l), or vehicle,respectively,(n=6,each).The changes of intestinal afferent discharge were observed after adding 5-HT(500μM)or BK(1μM)or luminal distension(0 cmH₂O～80cmH₂O).The afferent nerve discharge was recorded using extracellular multi-unit mesenteric afferent nerve recording.Experiment in vivo:SD rat intestinal myoelectric motility was recorded using PowerLab system(Australia),and the effect of CB receptor agonist HU210(100μg/kg)or CB receptor antagonist AM 251(3mg/kg)was observed after their intraperitoneal injection respectively(n=6, each).Results in vitro:Using CB-1 receptor antagonist SR141716A,the intestinal afferent nerve discharge induced by bradykinin stimulation was reduced significantly (P＜0.05),and the same effect was also found in the afferent nerve discharge induced by the noxious mechanical distension of the intestinal loop(30 to 80cmH₂O) (P＜0.05).in vivo:CB receptor antagonist AM 251(3mg/kg)increased the frequencies and amplitudes of the intestinal spike activities in rats.While CB receptor agonist HU210(100μg/kg)got the oppositive effection on the frequencies and amplitudes of the intestinal myoelectric activities in rats.Conclusion The endocannabinoid system took part in the regulation of the gastrointestinal motility.This system seemed to play an inhibiting role in the intestinal myoelectric activity in rats.It had no effect on the baseline of the afferent discharge from the isolated intestinal segments of rats.But the increment of the afferent discharge induced by some stimulatiors was attenuated by the CB antagonist significantly,which suggested that the increased activity of the local endocannabinoid system may be involved in the pathogenesis of the small intestinal hypersensitivity.