Nerve injury disrupts temporal processing in the spinal cord dorsal horn through alterations in PV+interneurons

Abstract

SummaryHow mechanical allodynia following nerve injury is encoded in patterns of neural activity in the spinal cord dorsal horn (DH) is not known. We addressed this using the spared nerve injury model of neuropathic pain andin vivoelectrophysiological recordings. Surprisingly, despite dramatic behavioral over-reactivity to mechanical stimuli following nerve injury, an overall increase in sensitivity or reactivity of DH neurons was not observed. We did, however, observe a marked decrease in correlated neural firing patterns, including the synchrony of mechanical stimulus-evoked firing, across the DH. Alterations in DH temporal firing patterns were recapitulated by silencing DH parvalbumin+(PV+) inhibitory interneurons, previously implicated in mechanical allodynia, as were allodynic pain-like behaviors in mice. These findings reveal decorrelated DH network activity, driven by alterations in PV+interneurons, as a prominent feature of neuropathic pain, and suggest that restoration of proper temporal activity is a potential treatment for chronic neuropathic pain.