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Objective: To determine if the perioperative administration of valproic acid reduces the incidence of chronic pain three months after amputation or revision surgery., Design: Multicenter, randomized, double-blind, placebo-controlled trial., Setting: Academic, military, and veteran medical centers., Subjects: One hundred twenty-eight patients undergoing amputation or amputation revision surgery at Duke University Hospital, Walter Reed National Military Medical Center, or the Durham Veterans Affairs Medical Center for either medical disease or trauma., Methods: Patients were randomized to placebo or valproic acid for the duration of hospitalization and treated with multimodal analgesic care, including regional anesthetic blockade. Primary outcome was the proportion of patients with chronic pain at three months (average numeric pain score intensity of 3/10 or greater). Secondary outcomes included functional trajectories (assessed with the Brief Pain Inventory short form and the Defense and Veterans Pain Rating Scale)., Results: The overall rate of chronic pain was 68.2% in the 107 patients who completed the end point assessment. There was no significant effect of perioperative valproic acid administration, with a rate of 65.45% (N = 36) in the treatment group and a rate of 71.15% (N = 37) in the placebo group. Overall, pain scores decreased from baseline to follow-up (median = -2 on the numeric pain scale). Patients additionally experienced improvements in self-perceived function., Conclusions: The rate of chronic pain after amputation surgery is not significantly improved with the perioperative administration of valproic acid. In this cohort treated with multimodal perioperative analgesia and regional anesthetic blockade, we observed improvements in both pain severity and function., (© 2019 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To define clinical phenotypes of postamputation pain and identify markers of risk for the development of chronic pain., Design: Cross-sectional study of military service members enrolled 3-18 months after traumatic amputation injury., Setting: Military Medical Center., Subjects: 124 recent active duty military service members., Methods: Study subjects completed multiple pain and psychometric questionnaires to assess the qualities of phantom and residual limb pain. Medical records were reviewed to determine the presence/absence of a regional catheter near the time of injury. Subtypes of residual limb pain (somatic, neuroma, and complex regional pain syndrome) were additionally analyzed and associated with clinical risk factors., Results: A majority of enrolled patients (64.5%) reported clinically significant pain (pain score ≥ 3 averaged over previous week). 61% experienced residual limb pain and 58% experienced phantom pain. When analysis of pain subtypes was performed in those with residual limb pain, we found evidence of a sensitized neuroma in 48.7%, somatic pain in 40.8%, and complex regional pain syndrome in 19.7% of individuals. The presence of clinically significant neuropathic residual limb pain was associated with symptoms of PTSD and depression. Neuropathic pain of any severity was associated with symptoms of all four assessed clinical risk factors: depression, PTSD, catastrophizing, and the absence of regional analgesia catheter., Conclusions: Most military service members in this cohort suffered both phantom and residual limb pain following amputation. Neuroma was a common cause of neuropathic pain in this group. Associated risk factors for significant neuropathic pain included PTSD and depression. PTSD, depression, catastrophizing, and the absence of a regional analgesia catheter were associated with neuropathic pain of any severity., (Published by Oxford University Press on behalf of the American Academy of Pain Medicine. 2016. This work is written by US Government employees and is in the public domain in the US.)