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

Ting Yi ^ab1, Mengping Lou ^a1, Xinyi Gao ^a, Liyuan Bao ^a, Heting Yan ^a, Teng Lin ^a, Yayue Yang ^a, Tianchi Gao ^a, Chenghao Wang ^a, Jianyu Zhu ^a, Yanqing Wang ^ab, Wenli Mi ^a

^aDepartment of Integrative Medicine and Neurobiology, School of Basic Medical Science, Institutes of Integrative Medicine, Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai, 200032, China

^bChinese Medicine Research Institute, Guangdong Pharmaceutical University, Guangzhou, 510006, China

Received 3 July 2024, Revised 1 February 2025, Accepted 5 February 2025, Available online 6 February 2025, Version of Record 11 February 2025.

Abstract

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.

Keywords

Chronic itch ; Astrocyte ; Rostral ventromedial medulla

Received 3 July 2024, Revised 1 February 2025, Accepted 5 February 2025, Available online 6 February 2025, Version of Record 11 February 2025.