OPRM1 and Anxiety: Clinically, people with high anxiety and chronic pain, including OA pain, have greater opioid consumption compared with people with comparable pain but less anxiety.8 This clinical problem was mimicked in a rodent model of high anxiety and OA-like pain; our mechanistic studies revealed multiple lines of evidence supporting altered endogenous opioid function, including increased phosphorylation at serine residue 375 of MOR, which is required for opioid-mediated desensitization,50 in the absence of previous exposure to exogenous opioid ligand.