| First Author | Gautam M | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 2911 |
| PubMed ID | 38575590 | Mgi Jnum | J:359258 |
| Mgi Id | MGI:7619375 | Doi | 10.1038/s41467-024-47245-0 |
| Citation | Gautam M, et al. (2024) Distinct local and global functions of mouse Abeta low-threshold mechanoreceptors in mechanical nociception. Nat Commun 15(1):2911 |
| abstractText | The roles of Abeta 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 Abeta-LTMRs in this regard. Genetic ablation of Split(Cre)-Abeta-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)-Abeta-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 Abeta-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 Abeta-LTMRs for treating mechanical hyperalgesia. |
