Chemogenetic tools to determine the neuroimmune basis of pathological pain

• Grant number: 20/13470-9
• Support Opportunities: Scholarships abroad - Research
• Start date: December 15, 2021
• End date: December 14, 2022
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Marucia Chacur
• Grantee: Marucia Chacur
• Host Investigator: Linda Rothblum Watkins
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Colorado Boulder, United States

Abstract

Chronic pain disorders are a public health problem due to its high prevalence, high economic cost, and negative impact on patient quality of life. Animal models of chronic inflammatory and neuropathic pain represent an unprecedented opportunity to identify novel mechanisms underlying both their production and their effective management. Recent development of genetic tools for high spatial and temporal control over neural activity have provided mechanistic insights into a number of clinical conditions, but have yet to gain traction in studying non-classical drivers of pain states, notably neuroimmune cells. In the present proposal we will use a novel chemogenetic tool, DREADD (Designer Receptors Exclusively Activated by Designer Drugs), that will allow us to isolate the functional role of microglia in the initiation and maintenance of pathological pain states. We will use viral-mediated gene transfer of an inhibitory DREADD construct (AAV-CD68-hM4Di-mCherry) whose expression is under the microglia-specific promoter CD68 in order to selectively visualize and manipulate microglia function. We will determine the contribution of microglia to CCI-induced neuropathic pain through the analyses of neuroimmune mRNA and protein markers along with behavior following DREADD-mediated inhibition. Since pain is mediated by complex, integrative brain processes, neuroimmune-specific DREADD constructs will be a valuable tool for identifying novel pain mechanisms. (AU)