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...

Full description

Saved in:
Bibliographic Details
Published inNature communications Vol. 15; no. 1; p. 2911
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
LanguageEnglish
Published London Nature Publishing Group UK 04.04.2024
Nature Publishing Group
Nature Portfolio
Subjects
Online AccessGet full text

Cover

Loading…
More Information
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.
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