Dynorphinergic neurons in lateral pons inhibit pain via a descending circuit

Chronic pain afflicts millions of patients, yet treatments are largely ineffective, and development of new, targeted therapies is limited by knowledge gaps in the neurobiology of pain. We have recently discovered a novel group of brainstem neurons in lateral pons, situated juxta the A5 noradrenergic cell group (LJA5 neurons), that are defined by their expression of prodynorphin and glutamic acid decarboxylase 1 (GAD1). Importantly, these neurons project to all levels of the spinal cord, in lamina 1 of the dorsal horn, and previous work has demonstrated that chemogenetic activation of this neuronal population suppressed capsaicin-induced mechanical, but not thermal, pain.