Amber Taylor,1 Anton H Westveld,2,6 Magdalena Szkudlinska,1 Prathima Guruguri,1 Emil Annabi,3 Amol Patwardhan,3 Theodore J Price,4 Hussein N Yassine51Department of Medicine, University of Arizona, Tucson, AZ, USA; 2Statistics Laboratory, Bio5 Institute, Statistics GIDP, University of Arizona, Tucson, AZ, USA; 3Department of Anesthesia, University of Arizona, Tucson, AZ, USA; 4Department of Pharmacology, University of Arizona, Tucson, AZ, USA; 5Department of Medicine, University of Southern California, LA, CA, USA; 6Faculty of ESTeM, University of Canberra, Canberra, ACT, AustraliaAbstract: Lumbar radiculopathy pain represents a major public health problem, with few effective long-term treatments. Preclinical neuropathic and postsurgical pain studies implicate the kinase adenosine monophosphate activated kinase (AMPK) as a potential pharmacological target for the treatment of chronic pain conditions. Metformin, which acts via AMPK, is a safe and clinically available drug used in the treatment of diabetes. Despite the strong preclinical rationale, the utility of metformin as a potential pain therapeutic has not yet been studied in humans. Our objective was to assess whether metformin is associated with decreased lumbar radiculopathy pain, in a retrospective chart review. We completed a retrospective chart review of patients who sought care from a university pain specialist for lumbar radiculopathy between 2008 and 2011. Patients on metformin at the time of visit to a university pain specialist were compared with patients who were not on metformin. We compared the pain outcomes in 46 patients on metformin and 94 patients not taking metformin therapy. The major finding was that metformin use was associated with a decrease in the mean of “pain now,” by −1.85 (confidence interval: −3.6 to −0.08) on a 0–10 visual analog scale, using a matched propensity scoring analysis and confirmed using a Bayesian analysis, with a significant mean decrease of −1.36 (credible interval: −2.6 to −0.03). Additionally, patients on metformin showed a non-statistically significant trend toward decreased pain on a variety of other pain descriptors. Our proof-of-concept findings suggest that metformin use is associated with a decrease in lumbar radiculopathy pain, providing a rational for larger retrospective trials in different pain populations and for prospective trials, to test the effectiveness of metformin in reducing neuropathic pain.Keywords: neuropathy, mTOR, adenosine monophosphate activated kinase, diabetes