Age-related sensory dysfunction reconfigures the spinal circuitry for touch, itch and pain

Abstract

Sensory dysfunction during aging results in sharp increases in the incidence of chronic itch and pain, which counterintuitively are associated with reduced sensitivity to light touch. While age-related changes in peripheral mechanosensory transmission have been described, the contribution central mechanisms make to altered itch and pain responses remains largely unknown. Here, we show that signalling from cutaneous touch receptors is essential for maintaining the cellular composition of the central somatosensory circuits that process itch and pain information in adult mice. In particular, the loss of excitatory signalling from Merkel cells during aging causes the degeneration of subsets of molecularly defined inhibitory and excitatory neurons in the dorsal spinal cord, including inhibitory neurons that express the neuropeptide NPY. Our demonstration that the activity-dependent loss of inhibitory NPY neurons drives itch and pain hypersensitivity in old animals reveals the mechanism by which aging reconfigures the central neuronal circuits that sense touch, itch and pain.