A population of primary afferent sensory neurons mediates pain relief through nocifensive coping behavior in mice

• 成果类型: Article
• 署名作者: Sueto, Daichi; Uchiyama, Sawako; Ono, Teruaki; Watanabe, Moeka; Sekine, Misuzu; Nishida, Yuto; Nomaki, Kohei; Shibata, Yuto; Tashima, Ryoichi; Fujimori, Kazuki; Nakashima, Yasuharu; Tsuda, Makoto
• 署名单位: Kyushu University; Kyushu University; Kyushu University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2601766123
• 发表日期: 2026-07-21
• 页码: e2601766123
• 关键词: pain-coping behavior; pain; spinal dorsal horn neurons; spinal gate control; Npy2r-Cre(+) primary afferents; SPINAL CIRCUITS; identification; touch; architecture; inhibition; mechanisms

摘要

When exposed to noxious cutaneous stimuli, animals exhibit nocifensive behaviors, including rapid defensive reflexes that limit tissue damage and subsequent coping behaviors-most commonly licking of the affected area-that alleviate pain. Despite its ubiquity, the neural mechanism underlying pain relief through licking remains poorly understood. Here, we demonstrate that Npy2r-Cre(+) primary sensory neurons in the dorsal root ganglion (DRG), a population of A beta fibers that includes touch-sensitive, rapidly adapting low-threshold mechanoreceptors, are critical for this process. Mice lacking Npy2r-Cre(+) neurons exhibited a significant prolongation of coping behavior duration, but not bout frequency, following intraplantar injection of capsaicin or formalin. Conversely, optogenetic activation of Npy2r-Cre(+) neurons produced attenuating effects on irritant-induced pain. Electrophysiological analyses revealed that Npy2r-Cre(+) neurons form functional synaptic connections with neurons in the substantia gelatinosa of the spinal dorsal horn (SDH) and that their activation suppressed C fiber-evoked excitation of neurons in lamina I of the SDH, a region implicated in nociceptive transmission to the brain. Together, these findings identify Npy2r-Cre(+) DRG neurons as a key neural substrate for gating nociceptive transmission in the SDH and mediating pain relief through coping behaviors.