A sleep-active basalocortical pathway crucial for generation and maintenance of chronic pain

Poor sleep is associated with the risk of developing chronic pain, but how sleep contributes to pain chronicity remains unclear. Here we show that following peripheral nerve injury, cholinergic neurons in the anterior nucleus basalis (aNB) of the basal forebrain are increasingly active during nonrapid eye movement (NREM) sleep in a mouse model of neuropathic pain. These neurons directly activate vasoactive intestinal polypeptide-expressing interneurons in the primary somatosensory cortex (S1), causing disinhibition of pyramidal neurons and allodynia. The hyperactivity of aNB neurons is caused by the increased inputs from the parabrachial nucleus (PB) driven by the injured peripheral afferents. Inhibition of this pathway during NREM sleep, but not wakefulness, corrects neuronal hyperactivation and alleviates pain. Our results reveal that the PB-aNB-S1 pathway during sleep is critical for the generation and maintenance of chronic pain. Inhibiting this pathway during the sleep phase could be important for treating neuropathic pain. Zhou et al. show that the generation and maintenance of chronic neuropathic pain after peripheral nerve injury is crucially dependent on the activation of a parabrachial nucleus-nucleus basalis-S1 pathway during non-REM sleep.

Automated summary

Poor sleep is associated with the risk of developing chronic pain. In a mouse model of neuropathic pain, cholinergic neurons in the basal forebrain are increasingly active during nonrapid eye movement (NREM) sleep. These neurons directly activate vasoactive intestinal polypeptide-expressing interneurons in the primary somatosensory cortex (S1), causing pain. The hyperactivity of these neurons is caused by inputs from the parabrachial nucleus (PB) driven by the injured peripheral nerves.