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Gut. 2009 Jun;58(6):751-61. doi: 10.1136/gut.2007.144543. Epub 2008 Oct 13.

Luminal hydrogen sulfide plays a pronociceptive role in mouse colon.

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1
Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan.

Abstract

OBJECTIVE:

Given recent evidence that hydrogen sulfide (H(2)S), a gasotransmitter, promotes somatic pain through redox modulation of T-type Ca(2+) channels, the roles of colonic luminal H(2)S in visceral nociceptive processing in mice were examined.

METHODS:

After intracolonic administration of NaHS, an H(2)S 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 Ca(2+) 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 Ca(2+) channels or ATP-sensitive K(+) (K(ATP)) channels. Intraperitoneal NaHS at 60 micromol/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 H(2)S/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.

PMID:
18852258
DOI:
10.1136/gut.2007.144543
[Indexed for MEDLINE]
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