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.

A subset of spinal dorsal horn interneurons crucial for gating touch-evoked pain-like behavior.

A cardinal, intractable symptom of neuropathic pain is mechanical allodynia, pain caused by innocuous stimuli via low-threshold mechanoreceptors such as Aβ fibers. However, the mechanism by which Aβ fiber-derived signals are converted to pain remains incompletely understood. Here we identify a subset of inhibitory interneurons in the spinal dorsal horn (SDH) operated by adeno-associated viral vectors incorporating a neuropeptide Y promoter (AAV-NpyP) and show that specific ablation or silencing of AAV-NpyP SDH interneurons converted touch-sensing Aβ fiber-derived signals to morphine-resistant pain-like behavioral responses.