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 Gu () and Wenqin Luo ()
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Mayank Gautam: University of Pennsylvania
Akihiro Yamada: University of Alabama at Birmingham
Ayaka I. Yamada: University of Alabama at Birmingham
Qinxue Wu: University of Pennsylvania
Kim Kridsada: University of Pennsylvania
Jennifer Ling: University of Alabama at Birmingham
Huasheng Yu: University of Pennsylvania
Peter Dong: University of Pennsylvania
Minghong Ma: University of Pennsylvania
Jianguo Gu: University of Alabama at Birmingham
Wenqin Luo: University of Pennsylvania

Nature Communications, 2024, vol. 15, issue 1, 1-19

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 SplitCre labeled mouse Aβ-LTMRs in this regard. Genetic ablation of SplitCre-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 SplitCre-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.

Date: 2024
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DOI: 10.1038/s41467-024-47245-0

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