A pontine center in descending pain control

Abstract

Pain sensation changes according to expectation, context, and mood, illustrating how top-down circuits affect somatosensory processing. Here, we used an intersectional strategy to identify anatomical and molecular-spatial features of supraspinal descending neurons activated by distinct noxious stimulation. This approach captured known descending pain pathways as well as spinal projecting neurons that are anatomically mapped to Barrington's nucleus in the dorsal pontine tegmentum. We determined that this population of neurons expresses corticotropin-releasing hormone in Barrington's nucleus (Bar^Crh) and exhibits time-locked firing in response to noxious stimulation. Chemogenetic activation of Bar^Crh neurons attenuated nocifensive responses as well as tactile neuropathic pain, while silencing these neurons resulted in thermal hyperalgesia and mechanical allodynia. Mechanistically, we demonstrated that pain-related input from the ventrolateral periaqueductal gray recruits Bar^Crh neurons, reduces ascending nociceptive transmission, and preferentially activates spinal dynorphin neurons to mediate analgesia. Our data expose a pontine inhibitory descending pathway that powerfully controls nocifensive sensory input to the brain.

Keywords: Barrington’s nucleus; Crh; descending pain modulation; dynorphin; periaqueductal gray; pontine; supraspinal.