RGS4 Maintains Chronic Pain Symptoms in Rodent Models

There is an imminent need for safe and efficient chronic pain medications. Regulator of G-protein signaling 4 (RGS4) is a multi-functional signal transduction protein, widely expressed in the pain matrix. Here, we demonstrate that RGS4 plays a prominentrole in the maintenance of chronic pain symptoms in male and female mice. Using genetically modified mice, we show a dynamicrole of RGS4 in recovery from symptoms of sensory hypersensitivity deriving from hindpaw inflammation or hindlimb nerveinjury. We also demonstrate an important role of RGS4 actions in gene expression patterns induced by chronic pain states in themouse thalamus. Our findings provide novel insight into mechanisms associated with the maintenance of chronic pain states anddemonstrate that interventions in RGS4 activity promote recovery from sensory hypersensitivity symptoms. Overall design: Using a mouse line carrying a floxed RGS4 gene and adeno-associated virus (AAV) vectors expressing Cre recombinase, we downregulated RGS4 expression in the VPL-THL (ventral posterolateral thalamic nuclei)