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

• Published in: Cell reports (Cambridge) 2024-02, Vol.43 (2), p.113718-113718, Article 113718
• Main Authors: Rankin, Genelle, Chirila, Anda M., Emanuel, Alan J., Zhang, Zihe, Woolf, Clifford J., Drugowitsch, Jan, Ginty, David D.
• Format: Article
• Language: English
• Subjects: Animals; CP: Neuroscience; dorsal horn inhibition; dorsal horn network activity; Hyperalgesia; in vivo electrophysiology; Interneurons; mechanical allodynia; Mice; Neuralgia; Posterior Horn Cells; Spinal Cord; Spinal Cord Dorsal Horn; Time Perception
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.113718

How mechanical allodynia following nerve injury is encoded in patterns of neural activity in the spinal cord dorsal horn (DH) remains incompletely understood. We address this in mice using the spared nerve injury model of neuropathic pain and in vivo electrophysiological recordings. Surprisingly, despite dramatic behavioral over-reactivity to mechanical stimuli following nerve injury, an overall increase in sensitivity or reactivity of DH neurons is not observed. We do, 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 are recapitulated by silencing DH parvalbumin+ (PV+) interneurons, previously implicated in mechanical allodynia, as are allodynic pain-like behaviors. These findings reveal decorrelated DH network activity, driven by alterations in PV+ interneurons, as a prominent feature of neuropathic pain and suggest restoration of proper temporal activity as a potential therapeutic strategy to treat chronic neuropathic pain. [Display omitted] •Nerve injury does not induce general over-reactivity in spinal cord interneurons•Spike timing and neural activity correlations are disrupted following nerve injury•PV+ interneurons exhibit reduced firing after nerve injury in vivo•Silencing PV+ interneurons disrupts spike timing and activity correlations Rankin et al. have identified reduced spike timing synchrony and correlated activity in spinal cord dorsal horn interneurons in a peripheral nerve injury model of neuropathic pain. Diminished reactivity of PV+ dorsal horn interneurons following nerve injury is responsible for the decorrelated spinal cord dorsal horn network activity.