A subset of spinal dorsal horn interneurons crucial for gating touch-evoked pain-like behavior
Ryoichi Tashima, K. Koga, Yu Yoshikawa, Misuzu Sekine, Moeka Watanabe, Hidetoshi Tozaki‐Saitoh, Hidemasa Furue, Toshiharu Yasaka, Makoto Tsuda
Abstract
Significance Neuropathic pain is a debilitating chronic pain condition occurring after nerve damage. Its cardinal symptom is touch-evoked pain (mechanical allodynia), which is refractory to available medications including morphine. The underlying mechanism for allodynia remains incompletely understood. Using our recently established optogenetic approach for allodynia, here we identify a subset of spinal dorsal horn inhibitory interneurons (AAV-NpyP + interneurons) that acts as a critical brake on conversion of touch-sensing Aβ fiber signals into pain-like behavior that is resistant to morphine. AAV-NpyP + interneuron activity was reduced in a neuropathic pain model, and, conversely, activation of AAV-NpyP + interneurons in this model reversed Aβ fiber-derived pain-like behavior. Our study reveals a mechanism for touch–pain conversion and may provide a therapeutic strategy for neuropathic allodynia.