Rostral ventromedial medulla astrocytes regulate chronic itch and anxiety-related behaviors

Itch (pruritus), a maladaptive and debilitating cutaneous symptom, is commonly associated with many skin conditions; however, the available therapies with sufficient efficacy are lacking. The role of astrocytes in the rostral ventromedial medulla (RVM), a crucial brain region in the descending pain modulation system, in chronic itch remains uncertain. In this study, we examined the chronic itch behavior and itch-related anxiety behavior in the diphenylcyclopripenone (DCP)-induced contact dermatitis mice, and also observed the activation of astrocytes in the RVM in the DCP mice. Reducing calcium signaling in astrocytes through global IP3R2 gene knockout, conditional astroglial IP3R2 gene knockout in the RVM, or microinjection of AAV-GfaABC1D-hPMCA2 w/b into the RVM, exhibited an anti-pruritic effect on the chronic itch. These findings suggest that RVM astrocytes play a role in regulating chronic itch, and interventions targeting astrocytic activation may offer potential relief for chronic itch.