Distinct Local and Global Functions of Aβ Low-Threshold Mechanoreceptors in Mechanical Pain Transmission.
| Autor: | Gautam M; University of Pennsylvania., Yamada A; University of Alabama at Birmingham., Yamada A; University of Alabama at Birmingham., Wu Q; University of Pennsylvania., Kridsada K; University of Pennsylvania., Ling J; University of Alabama at Birmingham., Yu H; University of Pennsylvania., Dong P; University of Pennsylvania., Ma M; University of Pennsylvania School of Medicine., Gu J; University of Alabama at Birmingham., Luo W; University of Pennsylvania. |
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| Jazyk: | angličtina |
| Zdroj: | Research square [Res Sq] 2023 Jun 15. Date of Electronic Publication: 2023 Jun 15. |
| DOI: | 10.21203/rs.3.rs-2939309/v1 |
| Abstrakt: | 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 Aβ-LTMRs in this regard. Genetic ablation of Split Cre -Aβ-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 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 new model, in which Aβ-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 Aβ-LTMRs for treating mechanical hyperalgesia. Competing Interests: Declaration of Interests The authors declare no competing interests. |
| Databáze: | MEDLINE |
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