Spinal ganglia control nociceptive input to the central nervous system

Abstract

AbstractAccumulating observations suggest that peripheral somatosensory ganglia may regulate pain transmission, yet direct evidence is sparse. Here we show that the peripheral afferent nociceptive information undergoes dynamic filtering within dorsal root ganglia (DRG) and suggest that this filtering occurs at the axonal bifurcations (t-junctions). Using synchronous in vivo electrophysiological recordings in the peripheral (spinal nerve) and central (dorsal root) processes of the sensory nerve, ganglionic transplantation of GABAergic progenitor cells, and optogenetics we demonstrate tonic and dynamic filtering of action potentials traveling through the DRG. Filtering induced by focal application of GABA or optogenetic GABA release from the DRG-transplanted GABAergic progenitor cells was specific to nociceptive fibers. Light-sheet imaging and computer modeling demonstrated that, compared to other somatosensory fiber types, nociceptors have shorter stem axons, making somatic control over t-junctional filtering more efficient. Optogenetically-induced GABA release within DRG from the transplanted GABAergic cells enhanced filtering and reduced both acute and chronic inflammatory and neuropathic pain in vivo. These findings support ‘gating’ of pain information by spinal ganglia and suggest new therapeutic approaches for pain relief.