A pontine center in descending pain control
Our perception of pain changes according to expectation, context and mood illustrating how top-down-circuits affect sensory processing. Here we developed an intersectional platform for identifying supraspinal descending neurons that are engaged when an animal experiences pain. Amongst these, we identified a cluster of cells in the pontine micturition center (Barrington's nucleus), expressing corticotropin-releasing-hormone (BarCrh) that detect painful but not innocuous stimuli. When activated, BarCrh-neurons attenuate nocifensive responses as well as tactile neuropathic pain. Mechanistically, pain related input from the ventrolateral periaqueductal gray activates BarCrh-neurons, which in turn project to the spinal dorsal horn to mediate analgesia. In combination, our data demonstrate that Barrington's nucleus is not just a relay station dedicated to triggering micturition but also powerfully controls painful sensory input to the brain. Overall design: AAV-retro-H2B-GFP was injected into the lumbar spinal cord of the TRAP2 mice strain. Upon pain activation, hindbrain descending neurons activated by different types of pain were captured by FACS and subject for 10x single nucleus RNA sequencing.