Hydrogen Sulfide Mediates Chronic Visceral Pain Induced By Mediate Chronic Visceral Pain Induced By Prenatal Maternal Stress In Rat Offspring

Background: Functional dyspepsia(FD) is one of a common functional gastrointestinal disease and is characterized by a chronic relapsing or recurrent abdominal pain or distension in the absence of any detectable structural/organic abnormalities.However, the mechanism of its etiology of abdominal pain in functional dyspepsia remains speculative. Increasing amounts of scientific evidence indicate that stressors presented during gestational periods could have long-term effects on the offspring’s tissure structure and function, which may perdispose to gastrointestinal diseases. The aim of the present study is to determine whether maternal psychosocial stress is a prenatanl factor affecting gastrointestinal sensitivity and possible mechanisms underlying prenatal maternal stress-induced visceral hyperalgesia in adult male offspring. Furthermore, the role of the endogenous H2 S and voltage-gated sodium channels signaling pathways in the pathogenesis of visceral hyperalgesia(VH) in the rat model of FD induced by prenatal maternal stress(PMS) were investigated in this study.Methods: Pregnant Sprague Dawley rats were exposed to heterotypic intermittent stress from gestational day 6 to 22. On postnatal week 6, visceral motor responses to gastric balloon distention(GD) were calculated by electromyographic(EMG) recordings.Tissues from gastric-specific dorsal root ganglion neurons(DRGs) were analyzed for CBS,voltage-gated sodium channel Na V 1.7 and Na V1.8 expression by Western blotting. AOAA,an antagonist of CBS, was used to detect the changes of the visceral hyperalgesia after intraperitoneal in adult male rat offspring. Besides, we collected 30 cases of gastric mucosa in FD patients and 27 normal cases to calculate the expression of CBS, Nav1.7 and Nav1.8by Western blotting.Results: PMS significantly increased visceromoter response to gastric balloon distention in adult male offspring rats from 6 weeks to 8 weeks. Compared with the controlrats, the expression of CBS, Nav1.7 and Nav1.8 proteins were enhanced greatly in the gastric-specific DR of PMS-induced adult male offsprings. When administration of AOAA,the EMG could attenuate in associated with the down-regulation of Nav1.7 and Nav1.8expression in the DRGs of PMS- induced rats. The expression of CBS, Nav1.7 and Nav1.8proteins in the gastric mucosa were 1.03±0.08, 0.95±0.08 and 0.79±0.11 VS 0.77±0.07,0.41±0.01 and 0.38±0.07 respectively in FD patients compared with the normal persons(*P<0.05, * P<0.05, * P<0.05).Conclusions: These results indicate that the presence of multiple psychophysical stressors during pregnancy was associated with higher visceral sensitivity, which is mediated by an upregualtion of CBS, Nav1.7 and Nav1.8. Thus, CBS-H2 S signaling might play a role in PMS-induced visceral pain in rat offspring through Nav1.7 and Nav1.8. This added knowledge would provide new strategies for treatment of chronic visceral pain in patients with functional bowel diseases such as FD.