Department of Physiology and Pharmacology Hotchkiss Brain Institute, Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Dermaxon LLC, Missoula, MT, USA.
Mol Brain. 2020 Sep 1;13(1):119. doi: 10.1186/s13041-020-00663-9.
Cav3.2 T-type calcium channels are important mediators of nociceptive signaling, but their roles in the transmission of itch remains poorly understood. Here we report a key involvement of these channels as key modulators of itch/pruritus-related behavior. We compared scratching behavior responses between wild type and Cav3.2 null mice in models of histamine- or chloroquine-induced itch. We also evaluated the effect of the T-type calcium channel blocker DX332 in male and female wild-type mice injected with either histamine or chloroquine. Cav3.2 null mice exhibited decreased scratching responses during both histamine- and chloroquine-induced acute itch. DX332 co-injected with the pruritogens inhibited scratching responses of male and female mice treated with either histamine or chloroquine. Altogether, our data provide strong evidence that Cav3.2 T-type channels exert an important role in modulating histamine-dependent and -independent itch transmission in the primary sensory afferent pathway, and highlight these channels as potential pharmacological targets to treat pruritus.
Cav3.2 T 型钙通道是伤害性信号传递的重要介质,但它们在瘙痒传递中的作用仍知之甚少。在这里,我们报告这些通道作为瘙痒/瘙痒相关行为的关键调节剂的关键参与。我们比较了 Cav3.2 敲除小鼠和野生型小鼠在组胺或氯喹诱导的瘙痒模型中的搔抓行为反应。我们还评估了 T 型钙通道阻滞剂 DX332 在注射组胺或氯喹的雄性和雌性野生型小鼠中的作用。在组胺和氯喹诱导的急性瘙痒中,Cav3.2 敲除小鼠的搔抓反应减少。DX332 与致痒原共同注射可抑制接受组胺或氯喹治疗的雄性和雌性小鼠的搔抓反应。总之,我们的数据提供了有力的证据,表明 Cav3.2 T 型通道在调节初级感觉传入通路中组胺依赖性和非依赖性瘙痒传递中发挥重要作用,并强调这些通道作为治疗瘙痒的潜在药物靶点。