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- Title
Plasticity in ventral pallidal cholinergic neuron-derived circuits contributes to comorbid chronic pain-like and depression-like behaviour in male mice.
- Authors
Ji, Ya-Wei; Shen, Zi-Lin; Zhang, Xue; Zhang, Kairan; Jia, Tao; Xu, Xiangying; Geng, Huizhen; Han, Yu; Yin, Cui; Yang, Jian-Jun; Cao, Jun-Li; Zhou, Chunyi; Xiao, Cheng
- 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. The cholinergic circuits involved in pain modulation remain poorly understood. Here, the authors show that reversal of plasticity in the ventral pallidum-basolateral amygdala cholinergic pathway relieves hyperalgesia and depression-like behaviours in a chronic pain mouse model.
- Subjects
PAIN perception; NICOTINIC acetylcholine receptors; CHOLINERGIC mechanisms; PAIN threshold; CHRONIC pain; COMORBIDITY; AMYGDALOID body
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-37968-x