Ethosuximide inhibits acute histamine- and chloroquine-induced scratching behavior in mice

Abstract

We have recently reported that the Cav3.2 T-type calcium channel which is well known for its key role in pain signalling, also mediates a critical function in the transmission of itch/pruritus. Here, we evaluated the effect of the clinically used anti-seizure medication ethosuximide, a well known inhibitor of T-type calcium channels, on male and female mice subjected to histaminergic- and non-histaminergic itch. When delivered intraperitoneally ethosuximide significantly reduced scratching behavior of mice of both sexes in response to subcutaneous injection of either histamine or chloroquine. When co-delivered subcutaneously together with either pruritogenic agent ethosuximide was also effective in inhibiting scratching responses in both male and female animals. Overall, our results are consistent with an important role of Cav3.2 T-type calcium channels in modulating histamine-dependent and histamine-independent itch transmission in the primary sensory pathway. Our findings also suggest that ethosuximide could be explored further as a possible therapeutic for the treatment of itch.

Keywords: Cav3.2 channel; Chloroquine; Ethosuximide; Histamine; Itch.

Fig. 1

Ethosuximide inhibits acute itch responses induced by histamine. Dose-dependent inhibition of the total time scratching the nape in (a, c) male or (b, d) female mice by ethosuximide when delivered (a, b) systemically (10.0–30.0 mg/kg, i.p.) before histamine treatment, or (c, d) when co-delivered (10.0–100.0 μg/co-injected) with histamine. Each bar represents the mean ± S.E.M. and is representative of two or three experimental runs. Numbers shown in the bars reflect numbers of mice. One-way ANOVA reveals significant differences

Fig. 2

Ethosuximide decreases scratching behavior induced by chloroquine. Dose-dependent inhibition of the total time scratching the nape in (a, c) male or (b, d) female mice by ethosuximide when delivered (a, b) systemically (10.0–30.0 mg/kg, i.p.) before chloroquine treatment, or (c, d) when co-delivered (10.0–100.0 μg/co-injected) with chloroquine. Each bar represents the mean ± S.E.M. and is representative of two experimental runs. Numbers shown in the bars reflect numbers of mice. Two-way ANOVA reveals statistical differences