Importance: Guidelines recommend using gabapentin to decrease postoperative pain and opioid use, but significant variation exists in clinical practice. Objective: To determine the effect of perioperative gabapentin on remote postoperative time to pain resolution and opioid cessation. Design, Setting, and Participants: A randomized, double-blind, placebo-controlled trial of perioperative gabapentin was conducted at a single-center, tertiary referral teaching hospital. A total of 1805 patients aged 18 to 75 years scheduled for surgery (thoracotomy, video-assisted thoracoscopic surgery, total hip replacement, total knee replacement, mastectomy, breast lumpectomy, hand surgery, carpal tunnel surgery, knee arthroscopy, shoulder arthroplasty, and shoulder arthroscopy) were screened. Participants were enrolled from May 25, 2010, to July 25, 2014, and followed up for 2 years postoperatively. Intention-to-treat analysis was used in evaluation of the findings. Interventions: Gabapentin, 1200 mg, preoperatively and 600 mg, 3 times a day postoperatively or active placebo (lorazepam, 0.5 mg) preoperatively followed by inactive placebo postoperatively for 72 hours. Main Outcomes and Measures: Primary outcome was time to pain resolution (5 consecutive reports of 0 of 10 possible levels of average pain at the surgical site on the numeric rating scale of pain). Secondary outcomes were time to opioid cessation (5 consecutive reports of no opioid use) and the proportion of participants with continued pain or opioid use at 6 months and 1 year. Results: Of 1805 patients screened for enrollment, 1383 were excluded, including 926 who did not meet inclusion criteria and 273 who declined to participate. Overall, 8% of patients randomized were lost to follow-up. A total of 202 patients were randomized to active placebo and 208 patients were randomized to gabapentin in the intention-to-treat analysis (mean [SD] age, 56.7 [11.7] years; 256 (62.4%) women and 154 (37.6%) men). Baseline characteristics of the groups were similar. Perioperative gabapentin did not affect time to pain cessation (hazard ratio [HR], 1.04; 95% CI, 0.82-1.33; P = .73) in the intention-to-treat analysis. However, participants receiving gabapentin had a 24% increase in the rate of opioid cessation after surgery (HR, 1.24; 95% CI, 1.00-1.54; P = .05). No significant differences were noted in the number of adverse events as well as the rate of medication discontinuation due to sedation or dizziness (placebo, 42 of 202 [20.8%]; gabapentin, 52 of 208 [25.0%]). Conclusions and Relevance: Perioperative administration of gabapentin had no effect on postoperative pain resolution, but it had a modest effect on promoting opioid cessation after surgery. The routine use of perioperative gabapentin may be warranted to promote opioid cessation and prevent chronic opioid use. Optimal dosing and timing of perioperative gabapentin in the context of specific operations to decrease opioid use should be addressed in further research. Trial Registration: clinicaltrials.gov Identifier: NCT01067144.

BACKGROUND: Chronic low back pain (CLBP) is the most common chronic pain condition and is often resistant to conventional treatments. Acupuncture is a popular alternative for treating CLBP but its mechanisms of action remain poorly understood. Evidence suggests that pain regulatory mechanisms (particularly the ascending and secondarily the descending pain modulatory pathways) and psychological mechanisms (e.g., expectations, pain catastrophizing and self-efficacy) may be involved in the pathogenesis of CLBP and its response to treatments. We will examine these mechanisms in the treatment of CLBP by electroacupuncture (EA). METHODS: We present the aims and methods of a placebo-controlled, participant-blinded and assessor-blinded mechanistic study. Adult patients with CLBP will be randomized to receiving 16 sessions of real (active) or sham (placebo) EA over the course of 8 weeks. The primary pain regulatory measure for which the study was powered is temporal summation (TS), which approximates ascending pain facilitation. Conditioned pain modulation (CPM), representing a descending pain modulatory pathway, will be our secondary pain regulatory measure. The primary psychological measure is expectations of benefit, and the secondary psychological measures are pain catastrophizing and self-efficacy in managing pain. Main clinical outcomes are back pain bothersomeness on a 0-100 visual analog scale (primary), Roland Morris Disability Questionnaire (secondary), and relevant items from the National Institutes of Health (NIH) Patient-Reported Outcome Measures Information System (secondary). We hypothesize that compared to sham, real EA will lead to greater reduction in TS after 8 treatment sessions (4 weeks); and that reduction in TS (and secondarily, increase in CPM) after 8 treatment sessions will mediate reduction in back pain bothersomeness from baseline to week 10 (clinical response) to EA. We also hypothesize that the three psychological factors are moderators of clinical response. With 100 treatment completers, the study is designed to have 80% power to detect a medium-sized between-group effect (d = 0.5) on temporal summation. DISCUSSION: To the best of our knowledge, this is the first appropriately powered, placebo-controlled clinical trial evaluating mechanisms of EA in the treatment of CLBP. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02503475 . Registered on 15 July 15 2015. Retrospectively registered.

Chronic pain, one of the most common reasons adults seek medical care (1), has been linked to restrictions in mobility and daily activities (2,3), dependence on opioids (4), anxiety and depression (2), and poor perceived health or reduced quality of life (2,3). Population-based estimates of chronic pain among U.S. adults range from 11% to 40% (5), with considerable population subgroup variation. As a result, the 2016 National Pain Strategy called for more precise prevalence estimates of chronic pain and high-impact chronic pain (i.e., chronic pain that frequently limits life or work activities) to reliably establish the prevalence of chronic pain and aid in the development and implementation of population-wide pain interventions (5). National estimates of high-impact chronic pain can help differentiate persons with limitations in major life domains, including work, social, recreational, and self-care activities from those who maintain normal life activities despite chronic pain, providing a better understanding of the population in need of pain services. To estimate the prevalence of chronic pain and high-impact chronic pain in the United States, CDC analyzed 2016 National Health Interview Survey (NHIS) data. An estimated 20.4% (50.0 million) of U.S. adults had chronic pain and 8.0% of U.S. adults (19.6 million) had high-impact chronic pain, with higher prevalences of both chronic pain and high-impact chronic pain reported among women, older adults, previously but not currently employed adults, adults living in poverty, adults with public health insurance, and rural residents. These findings could be used to target pain management interventions.

BACKGROUND: Persistent opioid use following surgery has received increasing attention from policymakers, researchers, and clinicians. Perioperative nerve blockade has been hypothesized to decrease the risk of persistent opioid use. We examined whether nerve blockade was associated with a decreased risk of persistent opioid use among patients undergoing shoulder arthroplasty, a procedure with high rates of persistent postoperative pain. METHODS: Using health care claims data, we constructed a sample of 6695 patients undergoing shoulder arthroplasty between 2002 and 2012 and used billing data to identify the utilization of nerve blockade. We then used a multivariable logistic regression to estimate the association between nerve blockade and 2 measures of opioid use: having filled at least 1 prescription for an opioid between postoperative days (PODs) 0 and 90, and between POD 91 and 365. This regression adjusted for a variety of potential confounders, such as preoperative opioid use and medical history. RESULTS: There was no association between nerve blockade and our 2 measures of persistent opioid use: adjusted odds ratio, 1.12 (97.5% confidence interval, 0.939-1.34; P = .15) for opioid use between POD 0 and 90, and adjusted odds ratio, 0.997 (97.5% confidence interval, 0.875-1.14; P = .95) for opioid use between POD 91 and 365. CONCLUSIONS: Although the use of perioperative nerve blockade may offer short-term benefits, in this study, it was not associated with a reduction in the risk of persistent opioid use for patients undergoing shoulder arthroplasty.

Objectives To identify trends in concurrent use of a benzodiazepine and an opioid and to identify the impact of these trends on admissions to hospital and emergency room visits for opioid overdose.Design Retrospective analysis of claims data, 2001-13.Setting Administrative health claims database.Participants 315 428 privately insured people aged 18-64 who were continuously enrolled in a health plan with medical and pharmacy benefits during the study period and who also filled at least one prescription for an opioid.Interventions Concurrent benzodiazepine/opioid use, defined as an overlap of at least one day in the time periods covered by prescriptions for each drug. Main outcome measures Annual percentage of opioid users with concurrent benzodiazepine use; annual incidence of visits to emergency room and inpatient admissions for opioid overdose.Results 9% of opioid users also used a benzodiazepine in 2001, increasing to 17% in 2013 (80% relative increase). This increase was driven mainly by increases among intermittent, as opposed to chronic, opioid users. Compared with opioid users who did not use benzodiazepines, concurrent use of both drugs was associated with an increased risk of an emergency room visit or inpatient admission for opioid overdose (adjusted odds ratio 2.14, 95% confidence interval 2.05 to 2.24; P\textless0.001) among all opioid users. The adjusted odds ratio for an emergency room visit or inpatient admission for opioid overdose was 1.42 (1.33 to 1.51; P\textless0.001) for intermittent opioid users and 1.81 (1.67 to 1.96; P\textless0.001) chronic opioid users. If this association is causal, elimination of concurrent benzodiazepine/opioid use could reduce the risk of emergency room visits related to opioid use and inpatient admissions for opioid overdose by an estimated 15% (95% confidence interval 14 to 16).Conclusions From 2001 to 2013, concurrent benzodiazepine/opioid use sharply increased in a large sample of privately insured patients in the US and significantly contributed to the overall population risk of opioid overdose.

BACKGROUND AND PURPOSE: Previous research has highlighted the importance of cognitive appraisal processes in determining the nature and effectiveness of coping with chronic pain. Two of the key variables implicated in appraisal of pain are catastrophizing and perceived injustice, which exacerbate the severity of pain-related distress and increase the risk of long-term disability through maladaptive behavioural responses. However, to date, the influences of these phenomena have not been examined concurrently, nor have they been related specifically to quality of life measures, such as life satisfaction. METHODS: Using data from an online survey of 330 individuals with chronic pain, structural path modelling techniques were used to examine the independent effects of pain catastrophizing, perceived injustice, and average pain intensity on life satisfaction. Two potential mediators of these relationships were examined: depressive symptoms and pain-related interference. RESULTS: Results indicated that depressive symptoms fully mediated the relationship between pain catastrophizing and life satisfaction, and pain interference fully mediated the relationship between pain intensity and life satisfaction. Both depressive symptoms and pain interference were found to significantly mediate the relationship between perceived injustice and life satisfaction, but perceived injustice continued to demonstrate a significant and negative relationship with life satisfaction, above and beyond the other study variables. CONCLUSIONS: The current findings highlight the distinct affective and behavioural mediators of pain and maladaptive cognitive appraisal processes in chronic pain, and highlight their importance in both perceptions of pain-related interference and longer-term quality of life.

Objective: There is an extensive relationship between chronic pain and depression; however, there is less research examining whether pain-specific factors, such as pain intensity, predict depression, above and beyond the role of normative factors, such as positive emotions. The current study characterized the independent contributions of pain intensity, pain catastrophizing, and a trait measure of happiness to self-rated depressive symptoms. Methods: We recruited and enrolled 70 volunteers across 3 groups of participants: two groups of patients with current low back pain (one group on opioids and one group opioid-naïve), and individuals in a methadone maintenance treatment program. Results: Of note, participants reporting concurrent opioid use reported significantly higher levels of depressive symptomatology, although study groups did not differ on any other clinical variables. In our path model, we failed to find direct relationships between pain (intensity or duration) and either trait happiness or depressive symptoms (p \textgreater .05). However, our analysis did reveal that individuals with chronic back pain who reported higher levels of trait happiness reported lower levels of depressive symptomatology; this effect was significantly mediated by lower levels of pain catastrophizing (standardized ab = -.144, p = .002). Conclusion: Our analysis suggests that trait happiness, while unrelated to ongoing pain, may predict a decreased vulnerability to depressive symptoms in individuals with chronic pain, which may operate via lower levels of pain catastrophizing.

Pain catastrophizing, a pattern of negative cognitive-emotional responses to actual or anticipated pain, maintains chronic pain and undermines response to treatments. Currently, precisely how pain catastrophizing influences pain processing is not well understood. In experimental settings, pain catastrophizing has been associated with amplified pain processing. This study sought to clarify pain processing mechanisms via experimental induction of pain catastrophizing. Forty women with chronic low back pain were assigned in blocks to an experimental condition, either a psychologist-led 10-minute pain catastrophizing induction or a control (10-minute rest period). All participants underwent a baseline round of several quantitative sensory testing (QST) tasks, followed by the pain catastrophizing induction or the rest period, and then a second round of the same QST tasks. The catastrophizing induction appeared to increase state pain catastrophizing levels. Changes in QST pain were detected for two of the QST tasks administered, weighted pin pain and mechanical allodynia. Although there is a need to replicate our preliminary results with a larger sample, study findings suggest a potential relationship between induced pain catastrophizing and central sensitization of pain. Clarification of the mechanisms through which catastrophizing affects pain modulatory systems may yield useful clinical insights into the treatment of chronic pain.

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 resolution (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 procedure, 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 \textgreater 6 weeks) versus 2.5 weeks (17% pain \textgreater 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. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

To date, there is no validated measure for pain catastrophizing at the daily level. The Pain Catastrophizing Scale (PCS) is widely used to measure trait pain catastrophizing. We sought to develop and validate a brief, daily version of the PCS for use in daily diary studies to facilitate research on mechanisms of catastrophizing treatment, individual differences in self-regulation, and to reveal the nuanced relationships between catastrophizing, correlates, and pain outcomes. After adapting the PCS for daily use, we evaluated the resulting 14 items using 3 rounds of cognitive interviews with 30 adults with chronic pain. We refined and tested the final daily PCS in 3 independent, prospective, cross-sectional, observational validation studies conducted in a combined total of 519 adults with chronic pain who completed online measures daily for 14 consecutive days. For study 1 (N = 131), exploratory factor analysis revealed adequate fit and-unexpectedly-unidimensionality for item responses to the daily PCS. Study 2 (N = 177) correlations indicated adequate association with related constructs (anger, anxiety, pain intensity, depression). Similarly, results for study 3 (N = 211) revealed expected correlations for daily PCS and measures of daily constructs including physical activity, sleep, energy level, and positive affect. Results from complex/multilevel confirmatory factor analysis confirmed good fit to a unidimensional model. Scores on the daily PCS were statistically comparable with and more parsimonious than the full 14-item version. Next steps include evaluation of score validity in populations with medical diagnoses, greater demographic diversity, and in patients with acute pain. PERSPECTIVE: This article describes the development and validation of a daily PCS. This daily measure may facilitate research that aims to characterize pain mechanisms, individual differences in self-regulation, adaptation, and nuanced relationships between catastrophizing, correlates, and pain outcomes.