Why does CB1R deletion cause severe pain specifically in females but not males?

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Description

The abstract reports that CB1R deletion in the mPFC-vlPAG pathway causes severe pain in female mice, suggesting sex-specific dependence on this circuit. The mechanistic basis for this sexual dimorphism in pain sensitivity remains unexplained.

Gap type: unexplained_observation Source paper: Sexually dimorphic cannabinoid 1 receptors on CaMKIIα neurons in the medial prefrontal cortex mediate sex differences in ACEA-induced antinociception in mice. (2026, Pain, PMID:41380094)

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