Cholinergic neurons in medial septum maintain anxiety-like behaviors induced by chronic inflammatory pain.

Cholinergic neurons in the medial septum (MS) participate in various cognitive and emotional behaviors, including innate anxiety. Chronic pain involves perceptual, cognitive and emotional components. Whether MS cholinergic system modulates pain-induced anxiety and the underlying neural circuits are involved remain unclear. In the present study, we showed that chemogenetic (DREADD) inhibition of MS cholinergic neurons relieved pain-induced anxiety-like behaviors in open field and elevated plus maze tests. Inhibiting the MS-rostral anterior cingulate cortex (rACC), but not the MS-ventral hippocampal CA1 pathway, achieved anxiolysis. These findings indicate the involvement of MS cholinergic system in modulating pain-induced anxiety-like behaviors.