Hydrogen sulfide-induced mechanical hyperalgesia and allodynia require activation of both Cav3.2 and TRPA1 channels in mice
Hydrogen sulfide-induced mechanical hyperalgesia and allodynia require activation of both Cav3.2 and TRPA1 channels in mice
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DOI：
10.1111/j.1476-5381.2012.01886.x
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发表时间：
2012-07-01
影响因子：
7.3
通讯作者：
Kawabata, Atsufumi
中科院分区：
文献类型：
--
作者：
Okubo, Kazumasa;Matsumura, Midori;Kawabata, Atsufumi
背景与目的硫化氢是一种气体递质，通过激活大鼠Cav3.2 t型钙通道促进躯体疼痛信号。鉴于H2S激活瞬时受体电位锚蛋白1 （TRPA1）通道的证据，我们询问除了Cav3.2通道外，TRPA1通道是否与H2S诱导的小鼠机械性痛觉过敏和异位性痛有关。实验方法采用von Frey试验评价小鼠机械痛觉过敏和异位性疼痛。反复鞘内注射反义寡脱氧核苷酸可使小鼠感觉神经元的Cav3.2或TRPA1通道沉默。足底给药NaHS可引起小鼠痛觉过敏和异位性痛，这一效应被NNC 550396或米贝弗拉底（t型钙通道阻滞剂）以及抗坏血酸或氯化锌（已知可选择性抑制t型钙通道的三种亚型中的Cav3.2通道）减弱或消除。感觉神经元中Cav3.2通道的沉默也能阻止nahs诱导的小鼠痛觉过敏和异位性疼痛。TRPA1通道阻滞剂AP18和感觉神经元TRPA1通道的沉默可显著抑制nahs诱导的小鼠痛觉过敏和异常性痛。结论和意义NaHS/H2S诱导小鼠机械性痛觉过敏和异常性痛需要激活Cav3.2和TRPA1通道。
BACKGROUND AND PURPOSE Hydrogen sulfide, a gasotransmitter, facilitates somatic pain signals via activation of Cav3.2 T-type calcium channels in rats. Given evidence for the activation of transient receptor potential ankyrin-1 (TRPA1) channels by H2S, we asked whether TRPA1 channels, in addition to Cav3.2 channels, contribute to the H2S-induced mechanical hyperalgesia and allodynia in mice. EXPERIMENTAL APPROACH Mechanical hyperalgesia and allodynia were evaluated by the von Frey test in mice. Cav3.2 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 550396 or mibefradil, T-type calcium channel blockers, and by ascorbic acid or zinc chloride, known to selectively inhibit Cav3.2 channels, out of the three isoforms of T-type calcium channels. Silencing of Cav3.2 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/H2S required activation of both Cav3.2 and TRPA1 channels in mice.