Distinct local and global functions of mouse Aβ low-threshold mechanoreceptors in mechanical nociception

• Published in: Nature communications 2024-04, Vol.15 (1), p.2911-2911, Article 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: Article
• Language: English
• Subjects: 14/19; 38/1; 38/32; 38/71; 631/378/2620/410; 631/378/3917; 64/110; 64/60; 9/74; 9/97; Ablation; Animal models; Chronic pain; Genetics; Humanities and Social Sciences; Hyperalgesia; Hypersensitivity; Inflammation; Information processing; Mechanoreceptors; multidisciplinary; Optics; Pain; Pain perception; Science; Science (multidisciplinary); Transmission
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-47245-0

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.