Distinct Local and Global Functions of Aβ Low-Threshold Mechanoreceptors in Mechanical Pain Transmission

• Published in: bioRxiv : the preprint server for biology
• Main Authors: Gautam, Mayank, Yamada, Akihiro, Yamada, Ayaka I, Wu, Qinxue, Kridsada, Kim, Ling, Jennifer, Yu, Huasheng, Dong, Peter, Ma, Minghong, Gu, Jianguo, Luo, Wenqin
• Format: Journal Article
• Language: English
• Published: United States 18.05.2023

The roles of Aβ low-threshold mechanoreceptors (LTMRs) in transmitting mechanical hyperalgesia and in alleviating chronic pain have been of great interest but remain contentious. Here we utilized intersectional genetic tools, optogenetics, and high-speed imaging to specifically examine functions of labeled Aβ-LTMRs in this regard. Genetic ablation of Split -Aβ-LTMRs increased mechanical pain but not thermosensation in both acute and chronic inflammatory pain conditions, indicating their modality-specific role in gating mechanical pain transmission. Local optogenetic activation of Split -Aβ-LTMRs triggered nociception after tissue inflammation, whereas their broad activation at the dorsal column still alleviated mechanical hypersensitivity of chronic inflammation. Taking all data into consideration, we propose a new model, in which Aβ-LTMRs play distinctive local and global roles in transmitting and alleviating mechanical hyperalgesia of chronic pain, respectively. Our model suggests a new strategy of global activation plus local inhibition of Aβ-LTMRs for treating mechanical hyperalgesia.