Involvement of Ca<sub>v</sub>3.2 T-Type Ca<sup>2+</sup> Channels and the Role of Endogenous Estrogen in Pruritus: Evidence from a Fundamental Study and Cross-Sectional Analysis of Pharmacy Claims Data

To clarify the roles of Ca_v3.2 T-type Ca²⁺ channels and endogenous estrogen in pruritus, we conducted a fundamental study employing mice and clinical cross-sectional analyses of pharmacy claims data. In mice, intradermal injection of sulfide (Na₂S), a Ca_v3.2 enhancer, caused itch responses, an effect blocked by KTtp38, a T-type Ca²⁺ channel inhibitor, and deletion of Ca_v3.2 gene. KTtp38 also suppressed itch responses following intradermal histamine or chloroquine. The sulfide-induced itch responses in female mice decreased by ovariectomy and/or repeated treatment with letrozole, an aromatase inhibitor. Cross-sectional analyses of pharmacy claims data of 357972 female patients aged 18 years and older, obtained from nationwide branches of a chain pharmacy group, showed significantly lower prescription rates of topical steroids used for treatment of pruritus and/or dermatitis in women 55 years and older than in women under 55 years, and in the users than non-users of estrogen suppressants. Multivariate logistic regression analysis in the users and non-users of estrogen suppressants after propensity score matching indicated significant negative association of topical steroid prescription with the use of estrogen suppressants. Together, the present fundamental and clinical studies suggest the involvement of Ca_v3.2 and the promotive role of estrogen in pruritus in mice and/or humans.