Distinct local and global functions of mouse Aβ low-threshold mechanoreceptors in mechanical nociception
Mayank Gautam, Akihiro Yamada, Ayaka I. Yamada, Qinxue Wu, Kim Kridsada, Jennifer Ling, Huasheng Yu, Peter Dong, Minghong Ma, Jianguo G. Gu, Wenqin Luo
Abstract
Abstract 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 Split Cre labeled mouse Aβ-LTMRs in this regard. Genetic ablation of Split Cre - Aβ-LTMRs increased mechanical nociception but not thermosensation in both acute and chronic inflammatory pain conditions, indicating a modality-specific role in gating mechanical nociception. Local optogenetic activation of Split Cre -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 model, in which Aβ-LTMRs play distinctive local and global roles in transmitting or alleviating mechanical hyperalgesia of chronic pain, respectively. Our model suggests a strategy of global activation plus local inhibition of Aβ-LTMRs for treating mechanical hyperalgesia.