Sensory plasticity of dorsal horn silent neurons as a critical mechanism for neuropathic pain

Nat Commun. 2026 Sep 3;17(1):10503. doi: 10.1038/s41467-026-76982-7.

ABSTRACT

The spinal cord dorsal horn (DH) integrates sensory processing but undergoes critical plasticity following nerve injury, leading to mechanical allodynia, or "touch-evoked pain". It has been proposed that after nerve injury, innocuous sensory neurons gain access to nociceptive-specific (NS) circuits in the DH due to altered spinal inhibitory controls, thereby converting touch into pain. It is however unclear how sensory processing is reorganized under these conditions to generate this symptom. In this study, we used two-photon calcium imaging in mice to show that spinal disinhibition or nerve injury converts most DH excitatory neurons into highly polymodal cells, and unmasks an unprecedented number of previously silent neurons responding to a wide dynamic range (WDR) of sensory modalities. Using computational modeling, we further show that neuropathic pain likely does not result primarily from the transformation of excitatory NS neurons into WDR neurons, but rather from the activation of this previously dormant circuit.

PMID:42834037 | DOI:10.1038/s41467-026-76982-7