Luminal hydrogen sulfide plays a pronociceptive role in mouse colon.
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.
Matsunami
M
M
Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan.
Tarui
T
T
Mitani
K
K
Nagasawa
K
K
Fukushima
O
O
Okubo
K
K
Yoshida
S
S
Takemura
M
M
Kawabata
A
A
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D003106:Colon / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000009:adverse effects* / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D020748:Mibefradil / Q000494:pharmacology; D051379:Mice; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D013440:Sulfides / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D013440:Sulfides; D020748:Mibefradil; D048049:Extracellular Signal-Regulated MAP Kinases; C025451:sodium bisulfide; D002211:Capsaicin; D006862:Hydrogen Sulfide