ArticleCNS neuroscience & therapeutics2026
Spinal Mechanisms of Testosterone Involved in Itch Regulation.
Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND AND
objectiveClinical and epidemiological data demonstrate that females exhibit higher itch sensitivity than males, and prior research has confirmed estrogen exacerbates pruritus to drive this sexual dimorphism. Nevertheless, it remains poorly defined whether testosterone, the primary androgen, exerts anti-pruritic effects and contributes to sex disparities in itch perception. This study therefore has three primary objectives: (1) to characterize testosterone's regulatory effects on acute and chronic itch across male and female mice; (2) to identify spinal androgen receptor-expressing neuronal populations mediating testosterone's anti-pruritic actions; (3) to elucidate the downstream GABAergic synaptic cascade by which testosterone suppresses spinal itch transmission.
methodsC57BL/6 mice and GRPR-GFP mice were used in this study. Behavioral tests were performed to evaluate the effects of exogenous testosterone administration, orchiectomy, androgen receptor (AR) antagonist flutamide, and GABA
resultsTestosterone contributed to sex differences in itch in mice. Exogenous testosterone suppressed histamine- or chloroquine-evoked acute itch and alleviated DNFB-induced chronic itch and anxiety-like behaviors. Orchiectomy enhanced itch sensitivity, which was reversed by testosterone replacement. AR was predominantly expressed on PAX2
conclusionTestosterone inhibits itch transmission at the spinal level by activating AR on GABAergic interneurons, enhancing GABA release, and subsequently suppressing GRPR
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