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


METHODS
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.


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
Mechanical hyperalgesia and allodynia induced by NaHS/H(2)S required activation of both Ca(v)3.2 and TRPA1 channels in mice.
Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, Higashi-Osaka, Japan.
Kazumasa
K
Okubo
Midori
M
Matsumura
Yudai
Y
Kawaishi
Yuka
Y
Aoki
Maho
M
Matsunami
Yasumasa
Y
Okawa
Fumiko
F
Sekiguchi
Atsufumi
A
Kawabata
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000502:physiology*; D020868:Gene Silencing; D006862:Hydrogen Sulfide; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D017879:Isothiocyanates / Q000494:pharmacology; D008297:Male; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011984:Sensory Receptor Cells / Q000502:physiology; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors / Q000502:physiology*
C504883:Cacna1h protein, mouse; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D017879:Isothiocyanates; D009838:Oligodeoxyribonucleotides; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C004471:allyl isothiocyanate; D006862:Hydrogen Sulfide