Long-term sustained pain following acute physical injury is a prominent feature of chronic pain conditions, but understanding the central mechanisms that signal enduring pain remains a challenge. Using ethologically relevant survival challenges in mice, we found that urgent threats such as hunger, thirst, and fear strongly and specifically suppress sustained pain regardless of the source of the injury. We identified a population of neurons in the brainstem parabrachial nucleus expressing Npy1r, a receptor for neuropeptide Y (NPY), that is persistently activated following injury and is necessary and sufficient for sustained pain responses. Hunger, thirst, and fear activate distinct populations of NPY-expressing neurons that project to the parabrachial nucleus, release NPY to inhibit Npy1r neurons, and suppress pain. This efficient mechanism ensures that animals can adaptively respond to survival threats and may potentially be leveraged to treat pain disorders.
Dr. Nitsan Goldstein is a postdoctoral fellow at the Massachusetts Institute of Technology in Cambridge, MA, USA. She received her PhD from the University of Pennsylvania, where she studied how hypothalamic hunger circuits are regulated by signals from the gut and interact with the rest of the brain to promote survival in a dynamic world. She is currently investigating the neural circuits underlying persistent pain states and endogenous mechanisms of analgesia.
