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bioRxiv · 10.1101/2023.05.16.540962

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

Gautam, M.·Yamada, A.·Yamada, A. I.·Wu, Q.·Kridsada, K.·Ling, J.·Yu, H.·Dong, P.·Ma, M.·Gu, J.·Luo, W.
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Abstract

The roles of A{beta} 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 A{beta}-LTMRs in this regard. Genetic ablation of SplitCre-A{beta}-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 SplitCre-A{beta}-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 A{beta}-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 A{beta}-LTMRs for treating mechanical hyperalgesia.

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Gautam, M., Yamada, A., Yamada, A. I., Wu, Q., Kridsada, K., Ling, J., Yu, H., Dong, P., Ma, M., Gu, J., Luo, W.. 2023-05-17. Distinct Local and Global Functions of Aβ Low-Threshold Mechanoreceptors in Mechanical Pain Transmission. https://doi.org/10.1101/2023.05.16.540962

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