Hydrogen sulfide-induced mechanical hyperalgesia and allodynia require activation of both Cav3.2 and TRPA1 channels in mice.

Abstract

BACKGROUND AND PURPOSE:

Hydrogen sulfide, a gasotransmitter, facilitates somatic pain signals via activation of Ca(v)3.2 T-type calcium channels in rats. Given evidence for the activation of transient receptor potential ankyrin-1 (TRPA1) channels by H(2)S, we asked whether TRPA1 channels, in addition to Ca(v)3.2 channels, contribute to the H(2)S-induced mechanical hyperalgesia and allodynia in mice.

EXPERIMENTAL APPROACH:

Mechanical hyperalgesia and allodynia were evaluated by the von Frey test in mice. Ca(v)3.2 or TRPA1 channels in the sensory neurons were silenced by repeated intrathecal administration of antisense oligodeoxynucleotides in mice.

KEY RESULTS:

Intraplantar administration of NaHS evoked hyperalgesia and allodynia in mice, an effect attenuated or abolished by NNC 55-0396 or mibefradil, T-type calcium channel blockers, and by ascorbic acid or zinc chloride, known to selectively inhibit Ca(v)3.2 channels, out of the three isoforms of T-type calcium channels. Silencing of Ca(v)3.2 channels in the sensory neurons also prevented the NaHS-induced hyperalgesia and allodynia in mice. The NaHS-induced hyperalgesia and allodynia in mice were significantly suppressed by AP18, a TRPA1 channel blocker, and by silencing of TRPA1 channels in the sensory neurons.

CONCLUSIONS AND IMPLICATIONS:

Mechanical hyperalgesia and allodynia induced by NaHS/H(2)S required activation of both Ca(v)3.2 and TRPA1 channels in mice.

• Authors: Kazumasa Okubo, Midori Matsumura, Yudai Kawaishi, Yuka Aoki, Maho Matsunami, Yasumasa Okawa, Fumiko Sekiguchi, Atsufumi Kawabata
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 166 Issue 5 Pg. 1738-43 (Jul 2012) ISSN: 1476-5381 [Electronic] England
• PMID: 22300342 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Chemical References

• Cacna1h protein, mouse
• Calcium Channel Blockers
• Calcium Channels, T-Type
• Isothiocyanates
• Oligodeoxyribonucleotides
• TRPA1 Cation Channel
• Transient Receptor Potential Channels
• Trpa1 protein, mouse
• allyl isothiocyanate
• Hydrogen Sulfide

Topics

• Animals
• Calcium Channel Blockers (pharmacology)
• Calcium Channels, T-Type (physiology)
• Gene Silencing
• Hydrogen Sulfide
• Hyperalgesia (chemically induced, physiopathology)
• Isothiocyanates (pharmacology)
• Male
• Mice
• Oligodeoxyribonucleotides (pharmacology)
• Sensory Receptor Cells (physiology)
• TRPA1 Cation Channel
• Transient Receptor Potential Channels (antagonists & inhibitors, physiology)