Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, Higashi-Osaka, Japan.
Br J Pharmacol. 2012 Jul;166(5):1738-43. doi: 10.1111/j.1476-5381.2012.01886.x.
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.
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.
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.
Mechanical hyperalgesia and allodynia induced by NaHS/H(2)S required activation of both Ca(v)3.2 and TRPA1 channels in mice.
作为一种气体递质，硫化氢通过激活大鼠中的 Ca(v)3.2 T 型钙通道促进躯体痛觉信号。鉴于硫化氢激活瞬时受体电位锚蛋白 1（TRPA1）通道的证据，我们想知道 TRPA1 通道除了 Ca(v)3.2 通道之外，是否也有助于 H₂S 诱导的小鼠机械性痛觉过敏和痛觉异常。
通过 von Frey 试验评估小鼠的机械性痛觉过敏和痛觉异常。通过在小鼠鞘内重复给予反义寡核苷酸来沉默感觉神经元中的 Ca(v)3.2 或 TRPA1 通道。
向足底内注射 NaHS 可引起小鼠痛觉过敏和痛觉异常，这种效应可被 NNC 55-0396 或 mibefradil（T 型钙通道阻滞剂）、抗坏血酸或氯化锌减弱或消除，已知这三种 T 型钙通道亚型中只有 Ca(v)3.2 通道能被这三种物质选择性抑制。感觉神经元中 Ca(v)3.2 通道的沉默也防止了 NaHS 引起的小鼠痛觉过敏和痛觉异常。TRPA1 通道阻滞剂 AP18 和感觉神经元中 TRPA1 通道的沉默显著抑制了 NaHS 引起的小鼠痛觉过敏和痛觉异常。
NaHS/H₂S 诱导的机械性痛觉过敏和痛觉异常需要小鼠 Ca(v)3.2 和 TRPA1 通道的共同激活。
