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. 2025 Mar 18;18(1):22.
doi: 10.1186/s13041-025-01196-9.

The terpenes alpha-bisabolol and camphene modulate pruritus via an action on Cav3.2 T-type calcium channels

Flavia T T Antunes  1 , Vinicius M Gadotti  1   2 , Gerald W Zamponi  3
Affiliations

The terpenes alpha-bisabolol and camphene modulate pruritus via an action on Cav3.2 T-type calcium channels

Flavia T T Antunes et al. Mol Brain. .

Abstract

Alpha-bisabolol and camphene have demonstrated analgesic effects in inflammatory pain models by blocking Cav3.2 calcium channels. As the pain pathway overlaps with mechanisms for itch, and because Cav3.2 channels have been associated with itch in our previous work, we aimed to investigate the potential anti-itch effects of these two terpenes. Although both terpenes failed to show anti-pruritogenic properties when dissolved in aqueous PBS, when diluted in Hydroxypropyl-beta-cyclodextrin their bioactivity significantly increased. Both compounds significantly reduced scratching in the histaminergic itch model, whether administered subcutaneously or intraperitoneally. Camphene reduced itching in the non-histaminergic model regardless of the route of administration, whereas alpha-bisabolol did not alleviate chloroquine-induced itching. When tested in Cav3.2-/- mice, neither camphene nor alpha-bisabolol significantly reduced histamine-induced scratching behavior. This suggests that the anti-pruritic actions of these terpenes may involve Cav3.2 block to mitigate itch.

Keywords: Alpha-bisabolol; Calcium channel; Camphene; Cav3.2; Itch.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no conflicts of interest. GWZ is co-founder and CSO of Zymedyne Therapeutics.

Figures

Fig. 1
Fig. 1
Anti-pruritic effects of terpenes injected subcutaneously in mouse models of histaminergic and non-histaminergic itch. Time scratching after different doses of (a) camphene or (b) alpha-bisabolol in histamine model. Time scratching with and without camphene (c) or alpha-bisabolol (d) at 100 µg (s.c.) in the chloroquine model. Each bar represents the mean ± S.E.M (n = 5–6). **p < 0.01, ***p < 0.001, ns = no significance. Panels a and b were analyzed by One-way ANOVA followed by a Tukey’s test. Panels c and d were analyzed by unpaired t-test
Fig. 2
Fig. 2
Anti-pruritic effects of terpenes injected intraperitoneally on histaminergic and non-histaminergic itch. Time scratching after different doses of (a) camphene or (b) alpha-bisabolol in the histamine model. Time scratching with and without camphene (c) or alpha-bisabolol (d) at 100 µg (i.p.) in the chloroquine model. Each bar represents the mean ± S.E.M (n = 5–6). *p < 0.05, **p < 0.01, ****p < 0.001, ns = no significance. Panels a and b were analyzed by One-way ANOVA followed by a Tukey’s test. Panels c and d were analyzed by unpaired t-test
Fig. 3
Fig. 3
Lack of effect of subcutaneously injected terpenes against histamine or chloroquine induced itch in Cav3.2 -/- mice. (a) Effect of camphene and alpha-bisabolol at 100 µg (s.c.) co-delivered with histamine. (b) Effect of camphene at 100 µg (s.c.) co-delivered with chloroquine. Each bar represents the mean ± S.E.M (n = 6). Ns = no significance. Panel a was analyzed by One-way ANOVA. Panels b was analyzed by unpaired t-test
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