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Hydrogen sulfide‐induced mechanical hyperalgesia and allodynia require activation of both Ca v 3.2 and TRPA1 channels in mice
Author(s) -
Okubo Kazumasa,
Matsumura Midori,
Kawaishi Yudai,
Aoki Yuka,
Matsunami Maho,
Okawa Yasumasa,
Sekiguchi Fumiko,
Kawabata Atsufumi
Publication year - 2012
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2012.01886.x
Subject(s) - hyperalgesia , mibefradil , chemistry , transient receptor potential channel , allodynia , t type calcium channel , pharmacology , nociception , voltage dependent calcium channel , calcium , medicine , receptor , biochemistry , organic chemistry
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.