Differential modification of ascending spinal outputs in acute and chronic pain states

Abstract

Pain hypersensitivity arises from the induction of plasticity in peripheral and spinal somatosensory neurons, which modifies nociceptive input to the brain, altering pain perception. We applied longitudinal calcium imaging of spinal dorsal projection neurons to determine whether and how the representation of somatosensory stimuli in the anterolateral tract, the principal pathway transmitting nociceptive signals to the brain, changes between distinct pain states. In healthy mice, we identified stable outputs selective for cooling or warming and a neuronal ensemble activated by noxious thermal and mechanical stimuli. Induction of acute peripheral sensitization by topical capsaicin transiently re-tuned nociceptive output neurons to encode low-intensity stimuli. In contrast, peripheral nerve injury resulted in a persistent suppression of innocuous spinal outputs coupled with persistent activation of a normally silent population of high-threshold neurons. These results demonstrate differential modulation of spinal outputs to the brain during nociceptive and neuropathic pain states.

Keywords: anterolateral tract; dorsal horn; dorsal root ganglia; neuropathic pain; plasticity; spinal cord.