Objective: Given our recent evidence that hydrogen sulfide (H2S), a gasotransmitter, promotes somatic pain through redox modulation of T-type Ca2+ channels, we examined roles for colonic luminal H2S in visceral nociceptive processing in mice.
Methods: After intracolonic (i.col.) administration of NaHS, a donor for H2S, visceral pain-like behavior and referred abdominal allodyina/hyperalgesia were evaluated. Phosphorylation of ERK in the spinal dorsal horn was determined immunohistochemically. The whole-cell recording technique was used to evaluate T-type Ca2+ currents (T-currents) in cultured dorsal root ganglion (DRG) neurons.
Results: Like capsaicin, NaHS, administered i.col. at 0.5-5 nmol/mouse, triggered visceral nociceptive behavior accompanied with referred allodynia/hyperalgesia in mice. Phosphorylation of ERK in the spinal dorsal horn was detected following i.col. NaHS or capsaicin. The behavioral effects of i.col. NaHS were abolished by a T-type channel blocker or an oxidant, but not inhibitors of L-type Ca2+ channels or ATP-sensitive K+ (KATP) channels. Intraperitoneal NaHS at 60 μmol/kg facilitated i.col. capsaicin-evoked visceral nociception, an effect being abolished by the T-type channel blocker, although it alone produced no behavioral effect. In DRG neurons, T-currents were enhanced by NaHS.
Conclusions: These findings suggest that colonic luminal H2S/NaHS plays pro-nociceptive roles, and imply that the underlying mechanisms might involve sensitization/activation of T-type channels probably in the primary afferents, aside from the issue of the selectivity of mibefradil.