Spinal Mechanisms Underlying Hydrogen Sulfide Signaling In Chronic Visceral Hypersensitivity Of Adult Rats With Neonatal Colonic Inflammation

Background: Irritable bowel syndrome(IBS) clinically manifests gastrointestinal disorder characterized by chronic abdominal pain. The pathogenesis of IBS remains elusive. Hydrogen sulfide(H2S) is reported to play an important role in development of visceral hyperalgesia. However, the role of H2 S at spinal cord level in visceral hyperalgesia is unknown. The aim of this study is to investigate how H2 S in spinal cord takes part in visceral hypersensitivity of adult rats with neonatal colonic inflammation(NCI).Methods: Visceral hypersensitivity was induced by induction of NCI and measured by grading the visceromotor response to colorectal distention(CRD). Double-blind method was used in the behavioral test. Expression of an endogenous H2 S synthesizing enzyme cystathionine β-synthetase(CBS) was determined by Western blotting technique. The excitability and synaptic transmission of neurons in the substantia gelatinosa(SG) of spinal cord were recorded by patch clamping technique.Results: NCI induced visceral hypersensitivity in adult rats at 6 weeks of age. The excitability and the glutamatergic synaptic activities of SG neurons in NCI rats were significantly increased 6 weeks after NCI. Meanwhile, expression of CBS at spinal dorsal horn was remarkably enhanced in NCI rats when compared with control rats,while the expression of CSE had no difference between them. Application of NaHS increased glutamatergic synaptic activities of SG neurons in healthy control rats most likely through a presynaptic mechanism. Importantly, intrathecal injection of NaHS induced visceral hypersensitivity in control rats, while intrathecal injection of AOAA(a CBS inhibitor) reversed the visceral hypersensitivity and suppressed the excited synaptic transmission in spinal cord dorsal horn of adult rats with NCI.Conclusion: These results suggest that NCI produced the visceral hypersensitivity, which is most likely mediated by the enhanced CBS-H2 S signaling at spinal dorsal horn level of adult rats. This and future investigation would provide a potential therapeutic strategy for treatment of chronic visceral pain in patients with IBS.