Chemogenetic silencing of spinal cord-projecting cortical neurons attenuates Aβ fiber-derived neuropathic allodynia in mice

Mechanical allodynia (pain caused by innocuous mechanical stimulation) is a hallmark symptom of neuropathic pain occurring following peripheral nerve injury (PNI). Using a transgenic mouse line, in which myelinated primary afferents, including Aβ fibers, express channelrhodopsin-2, we found that illumination of the plantar skin of mice following PNI produced an Aβ fiber-mediated pain-like withdrawal behavior and increased c-FOS⁺ neurons in the superficial spinal dorsal horn (SDH). These two responses were attenuated by chemogenetic silencing of primary sensory cortex (S1) neurons projecting directly to the SDH. These findings indicate that spinally projecting cortical S1 neurons contribute to Aβ fiber-derived neuropathic allodynia.