Cav3.2\u2009T-type calcium channels control acute itch in mice

Vinicius M Gadotti,Nicholas B Wageling,Dylan Budke,Joanna M Kreitinger,Gerald W Zamponi,Philippe Diaz

doi:10.1186/s13041-020-00663-9

Vinicius M Gadotti, Nicholas B Wageling + Show 4 more

Open Access

https://doi.org/10.1186/s13041-020-00663-9

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Abstract

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.

Highlights

Acute itch serves a protective function in response to events such as insect bites, allergic reactions, or skin borne parasites [1, 2]
We first determined whether deletion of Cav3.2 channels in mice affects scratching behavior induced by histamine or chloroquine injection
In a separate series of experiments, we evaluated the effect of the T-type channel blocker DX332 (a.k.a. compound 9 in Ref [13]) in male and female wild-type mice

Summary

Introduction

Acute itch (pruritus) serves a protective function in response to events such as insect bites, allergic reactions, or skin borne parasites [1, 2]. These findings suggest that T-type calcium channels may be important for the activity of pruriceptive neurons, we sought to determine whether Cav3.2 calcium channels are involved in chloroquineand histamine-induced itch.

Results

Conclusion