EDITOR’S CHOICE A Double-Blind Placebo Randomized Controlled Trial of Minocycline to Reduce Pain After Carpal Tunnel and Trigger Finger Release Catherine M. Curtin, MD, *† Debbie Kenney,‡ Paola Suarez, MPH,§ Vincent R. Hentz, MD, *† Tina Hernandez-Boussard, PhD,§ Sean Mackey, MD, PhD,k Ian R. Carroll, MD, MSk Purpose Minocycline is a microglial cell inhibitor and decreases pain behaviors in animal models. Minocycline might represent an intervention for reducing postoperative pain. This trial tested whether perioperative administration of minocycline reduced time to pain reso- lution (TPR) after standardized hand surgeries with known prolonged pain profiles: carpal tunnel release (CTR) and trigger finger release (TFR). Methods This double-blinded randomized controlled trial included patients undergoing CTR or TFR under local anesthesia. Before surgery, participants recorded psychological and pain measures. Participants received oral minocycline, 200 mg, or placebo 2 hours prior to pro- cedure, and then 100 mg of minocycline or placebo 2 times a day for 5 days. After surgery, participants were called daily assessing their pain. The primary end point of TPR was when participants had 3 consecutive days of 0 postsurgical pain. Futility analysis and Kaplan-Meier analyses were performed. Results A total of 131 participants were randomized and 56 placebo and 58 controls were analyzed. Median TPR for CTR was 3 weeks, with 15% having pain more than 6 weeks. Median TPR for TFR was 2 weeks with 18% having pain more than 6 weeks. The overall median TPR for the placebo group was 2 weeks (10% pain > 6 weeks) versus 2.5 weeks (17% pain > 6 weeks) for the minocycline group. Futility analysis found that the likelihood of a true underlying clinically meaningful reduction in TPR owing to minocycline was only 3.5%. Survival analysis found minocycline did not reduce TPR. However, subgroup analysis of those with elevated posttraumatic distress scores found the minocycline group had longer TPR. Conclusions Oral administration of minocycline did not reduce TPR after minor hand surgery. There was evidence that minocycline might increase length of pain in those with increased posttraumatic stress disorder symptoms. (J Hand Surg Am. 2017;42(3):166e174. Copyright Ó 2017 by the American Society for Surgery of the Hand. All rights reserved.) Type of study/level of evidence Therapeutic I. Key words Minocycline, carpal tunnel release, postoperative pain, glial cell inhibitor. From the *Department of Surgery, Palo Alto VA; the †Division of Plastic Surgery, Department of Surgery; the ‡Department of Orthopedic Surgery; the §Department of Surgery; and the kDivision of Pain Management, Department of Anesthesiology, Stanford University, Palo Alto, CA. Received for publication March 4, 2016; accepted in revised form December 29, 2016. C.M.C. received support through an RR&D pilot grant RX000487 from the U.S. Department of Veterans Affairs Rehabilitation and Research and Development Service. The contents of this work do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. Corresponding author: Catherine M. Curtin, MD, Suite 400, 770 Welch Rd., Palo Alto, CA 94304; e-mail: curtincatherine@yahoo.com. 0363-5023/17/4203-0003$36.00/0 http://dx.doi.org/10.1016/j.jhsa.2016.12.011 166 r Ó 2017 ASSH r Published by Elsevier, Inc. All rights reserved.