Visceral
hypersensitivity is one of the pivotal pathophysiological features of
visceral pain in
irritable bowel syndrome (IBS). Small-conductance Ca2+-activated K+ channel (SK) is critical for a variety of functions in the central nervous system (CNS), nonetheless, whether it is involved in the pathogenesis of visceral
hypersensitivity remain elusive. In this study, we examined mechanism of SK2 in hypothalamic paraventricular nucleus (PVN) in the pathogenesis of visceral
hypersensitivity induced by neonatal colorectal distension (CRD). Rats undergoing neonatal CRD presented with visceral
hypersensitivity as well as downregulated membrane SK2 channel and p-PKA. Intra-PVN administration of either the
membrane protein transport inhibitor
dynasore or the SK2 activator
1-EBIO upregulated the expression of membrane SK2 in PVN and mitigated visceral
hypersensitivity. In addition,
1-EBIO administration reversed the increase in neuronal firing rates in PVN in rats undergoing neonatal CRD. On the contrary, intra-PVN administration of either the SK2 inhibitor
apamin or PKA activator 8-Br-cAMP exacerbated the visceral
hypersensitivity. Taken together, these findings demonstrated that visceral
hypersensitivity is related to the downregulation of membrane SK2 in PVN, which may be attributed to the activation of PKA; pharmacologic activation of SK2 alleviated visceral
hypersensitivity, which brings prospect of SK2 activators as a new intervention for
visceral pain.