Distinct local and global functions of mouse Aβ low-threshold mechanoreceptors in mechanical nociception
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...
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Published in | Nature communications Vol. 15; no. 1; p. 2911 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
04.04.2024
Nature Publishing Group Nature Portfolio |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
The mechanism underlying mechanical hyperalgesia is not fully understood. Here authors show opposing roles of tactile afferents in mechanical nociception using mouse pain models. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-024-47245-0 |