Luminal hydrogen sulfide plays a pronociceptive role in mouse colon
- M Matsunami1,
- T Tarui1,
- K Mitani1,
- K Nagasawa1,
- O Fukushima1,
- K Okubo1,
- S Yoshida2,
- M Takemura3,
- A Kawabata1
- 1Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, Higashi-Osaka, Japan
- 2Department of Life Science, Kinki University School of Science and Engineering, Higashi-Osaka, Japan
- 3Department of Anatomy and Neurobiology, Osaka University Graduate School of Dentistry, Suita, Japan
- Professor A Kawabata, Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan;
- Revised 9 August 2008
- Accepted 16 September 2008
- Published Online First 13 October 2008
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+ (KATP) channels. Intraperitoneal NaHS at 60 μmol/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.
Competing interests: None.
See Commentary, p 744