TrkA-ing pain : an optobiological approach for probing the NGF/TrkA pathway in relation to pain
Abstract/Contents
- Abstract
- Chronic pain is a prevalent problem that plagues modern society, and there is a need for better understanding its mechanisms to produce alternative therapeutics for managing pain. Nerve Growth Factor (NGF) and its primary receptor, Tropomyosin Receptor Kinase A (TrkA) are known to be potent mediators of chronic pain, but there is a lack of established methods for precisely perturbing the NGF/TrkA signaling pathway in the study of pain and nociception. Optobiological tools that leverage light-induced protein-protein interactions allow for precise spatial and temporal control. Previously, our lab reported a blue-light activated version of TrkA generated using the improved Light inducible Dimer (iLiD) system, opto-iTrkA, and demonstrated its ability to activate similar downstream survival and differentiation pathways to native NGF/TrkA signaling in a cellular model. This work aims to extend the use of opto-iTrkA as a tool to studying nociceptive pathways \textit{in vitro} and pain \textit{in vivo}. We show that opto-iTrkA activation orthogonal to NGF/TrkA activation is able to sensitize the Transient Receptor Potential Vanilloid 1 (TRPV1) channel in cellular models, cause the transduction of phospho-ERK signals from axonal terminals to the soma in cultured sensory neurons, and also induce mechanical sensitization in mice expressing opto-iTrkA in the peripheral nervous system. We hope that this demonstrates the utility of opto-iTrkA as a tool to expand the toolbox for dissecting nociceptive pathways and pain.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Liu, Aofei |
|---|---|
| Degree supervisor | Cui, Bianxiao |
| Thesis advisor | Cui, Bianxiao |
| Thesis advisor | Bertozzi, Carolyn |
| Thesis advisor | Boxer, Steven |
| Degree committee member | Bertozzi, Carolyn |
| Degree committee member | Boxer, Steven |
| Associated with | Stanford University, School of Humanities and Sciences |
| Associated with | Stanford University, Department of Chemistry |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Aofei Liu. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/ww775my6366 |
Access conditions
- Copyright
- © 2023 by Aofei Liu
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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