Plasticity in ventral pallidal cholinergic neuron-derived circuits contributes to comorbid chronic pain-like and depression-like behaviour in male mice PMID: 37069246

ADC Targets in Oncology

2026-04-10

Plasticity in ventral pallidal cholinergic neuron-derived circuits contributes to comorbid chronic pain-like and depression-like behaviour in male mice

Nat Commun. 2023 Apr 17;14(1):2182. doi: 10.1038/s41467-023-37968-x.

Ya-Wei Ji ^# ¹ , Zi-Lin Shen ^# ¹ , Xue Zhang ¹ , Kairan Zhang ¹ , Tao Jia ¹ , Xiangying Xu ¹ , Huizhen Geng ¹ , Yu Han ¹ , Cui Yin ¹ ² ³ , Jian-Jun Yang ⁴ , Jun-Li Cao ⁵ ⁶ ⁷ , Chunyi Zhou ⁸ ⁹ ¹⁰ , Cheng Xiao ¹¹ ¹² ¹³

Affiliations

1. Jiangsu Key Laboratory of Anesthesiology, Xuzhou Medical University, 221004, Xuzhou, China.
2. Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China.
3. NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China.
4. Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
5. Jiangsu Key Laboratory of Anesthesiology, Xuzhou Medical University, 221004, Xuzhou, China. [email protected].
6. Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China. [email protected].
7. NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China. [email protected].
8. Jiangsu Key Laboratory of Anesthesiology, Xuzhou Medical University, 221004, Xuzhou, China. [email protected].
9. Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China. [email protected].
10. NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China. [email protected].
11. Jiangsu Key Laboratory of Anesthesiology, Xuzhou Medical University, 221004, Xuzhou, China. [email protected].
12. Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China. [email protected].
13. NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, 221004, Xuzhou, Jiangsu, China. [email protected].
# Contributed equally.

Abstract

Nucleus- and cell-specific interrogation of individual basal forebrain (BF) cholinergic circuits is crucial for refining targets to treat comorbid chronic pain-like and depression-like behaviour. As the ventral pallidum (VP) in the BF regulates pain perception and emotions, we aim to address the role of VP-derived cholinergic circuits in hyperalgesia and depression-like behaviour in chronic pain mouse model. In male mice, VP cholinergic neurons innervate local non-cholinergic neurons and modulate downstream basolateral amygdala (BLA) neurons through nicotinic acetylcholine receptors. These cholinergic circuits are mobilized by pain-like stimuli and become hyperactive during persistent pain. Acute stimulation of VP cholinergic neurons and the VP-BLA cholinergic projection reduces pain threshold in naïve mice whereas inhibition of the circuits elevated pain threshold in pain-like states. Multi-day repetitive modulation of the VP-BLA cholinergic pathway regulates depression-like behaviour in persistent pain. Therefore, VP-derived cholinergic circuits are implicated in comorbid hyperalgesia and depression-like behaviour in chronic pain mouse model.