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Chemogenetic and Optogenetic Manipulations of Microglia in Chronic Pain
Sebastian Parusel1,2, Min-Hee Yi1, Christine L Hunt3
1Department of Neurology, Mayo Clinic, Rochester, MN, 55905, USA.
Abstract:
Chronic pain relief remains an unmet medical need. Current research points to a substantial contribution of glia-neuron interaction in its pathogenesis. Particularly, microglia play a crucial role in the development of chronic pain. To better understand the microglial contribution to chronic pain, specific regional and temporal manipulations of microglia are necessary. Recently, two new approaches have emerged that meet these demands. Chemogenetic tools allow the expression of designer receptors exclusively activated by designer drugs (DREADDs) specifically in microglia. Similarly, optogenetic tools allow for microglial manipulation via the activation of artificially expressed, light-sensitive proteins. Chemo- and optogenetic manipulations of microglia in vivo are powerful in interrogating microglial function in chronic pain. This review summarizes these emerging tools in studying the role of microglia in chronic pain and highlights their potential applications in microglia-related neurological disorders.
Insights
New chemogenetic and optogenetic tools enable precise manipulation of microglia, offering powerful methods to study their role in chronic pain and related neurological disorders.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Chronic pain is a significant unmet medical need.
- Glia-neuron interactions, especially involving microglia, are implicated in chronic pain pathogenesis.
- Targeting microglial function is crucial for developing novel pain therapies.
Purpose of the Study:
- To review emerging chemogenetic and optogenetic tools for microglial manipulation.
- To highlight the application of these tools in studying microglial roles in chronic pain.
- To discuss their potential in understanding microglia-related neurological disorders.
Main Methods:
- Chemogenetics: Utilizing designer receptors exclusively activated by designer drugs (DREADDs) for specific microglial expression.
- Optogenetics: Employing light-sensitive proteins for targeted microglial manipulation in vivo.
- In vivo studies: Applying these techniques to interrogate microglial function in chronic pain models.
Main Results:
- Chemogenetic and optogenetic tools allow for precise temporal and regional control over microglial activity.
- These methods provide unprecedented ability to investigate the causal role of microglia in chronic pain.
- The review synthesizes current advancements in these powerful research approaches.
Conclusions:
- Chemogenetic and optogenetic tools are transformative for studying microglial function in chronic pain.
- These techniques offer significant potential for advancing research into microglia-related neurological disorders.
- Further application of these methods is expected to accelerate the development of new pain treatments.
