Chemogenetic and Optogenetic Manipulations of Microglia in Chronic Pain

 Sebastian Parusel1,2 · Min‑Hee Yi1  · Christine L. Hunt3  · Long‑Jun Wu1,4,5
1 Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA 
2 Faculty of Psychology and Neuroscience, Maastricht University, Maastricht MD, 6200, The Netherlands 
3 Department of Pain Medicine, Mayo Clinic, Jacksonville, FL 32224, USA 
4 Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA 
5 Department of Immunology, 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.

Keywords
Chronic pain; Microglia; Optogenetics; Chemogenetics; DREADDs; ReaChR