Luminal hydrogen sulfide plays a pronociceptive role in mouse colon

Objective: Given recent evidence that hydrogen sulfide (H2S), a gasotransmitter, promotes somatic pain through redox modulation of T-type Ca2+ channels, the roles of colonic luminal H2S in visceral nociceptive processing in mice were examined. Methods: After intracolonic administration of NaHS, an H2S donor, visceral pain-like behaviour and referred abdominal allodynia/hyperalgesia were evaluated. Phosphorylation of extracellular signal-regulated protein kinase (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 intracolonically at 0.5-5 nmol per mouse, triggered visceral nociceptive behaviour accompanied by referred allodynia/hyperalgesia in mice. Phosphorylation of ERK in the spinal dorsal horn was detected following intracolonic NaHS or capsaicin. The behavioural effects of intracolonic NaHS were abolished by a T-type channel blocker or an oxidant, but not inhibitors of L-type Ca2+ channels or ATP-sensitive K+ (K-ATP) channels. Intraperitoneal NaHS at 60 mu mol/kg facilitated intracolonic capsaicin-evoked visceral nociception, an effect abolished by the T-type channel blocker, although it alone produced no behavioural effect. In DRG neurons, T-currents were enhanced by NaHS. Conclusions: These findings suggest that colonic luminal H2S/NaHS plays pronociceptive roles, and imply that the underlying mechanisms might involve sensitisation/activation of T-type channels probably in the primary afferents, aside from the issue of the selectivity of mibefradil.