# Publications by Year: 2017

## 2017

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.
Sun EC, Dixit A, Humphreys K, Darnall BD, Baker LC, Mackey S. Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. BMJ. 2017;356:j760.
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.
Tran P, Sturgeon JA, Nilakantan A, Foote A, Mackey S, Johnson K. Pain catastrophizing mediates the relationship between trait happiness and depressive symptoms in individuals with current pain. J. Appl. Biobehav. Res. 2017;22(4).
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.
Taub CJ, Sturgeon JA, Johnson KA, Mackey SC, Darnall BD. Effects of a Pain Catastrophizing Induction on Sensory Testing in Women with Chronic Low Back Pain: A Pilot Study. Pain Res. Manag. 2017;2017:7892494.
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.
Darnall BD, Sturgeon JA, Cook KF, et al. Development and Validation of a Daily Pain Catastrophizing Scale. J. Pain. 2017;18(9):1139-1149.
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.
Davis KD, Flor H, Greely HT, et al. Brain imaging tests for chronic pain: medical, legal and ethical issues and recommendations. Nat. Rev. Neurol. 2017;13(10):624-638.
Chronic pain is the greatest source of disability globally and claims related to chronic pain feature in many insurance and medico-legal cases. Brain imaging (for example, functional MRI, PET, EEG and magnetoencephalography) is widely considered to have potential for diagnosis, prognostication, and prediction of treatment outcome in patients with chronic pain. In this Consensus Statement, a presidential task force of the International Association for the Study of Pain examines the capabilities of brain imaging in the diagnosis of chronic pain, and the ethical and legal implications of its use in this way. The task force emphasizes that the use of brain imaging in this context is in a discovery phase, but has the potential to increase our understanding of the neural underpinnings of chronic pain, inform the development of therapeutic agents, and predict treatment outcomes for use in personalized pain management. The task force proposes standards of evidence that must be satisfied before any brain imaging measure can be considered suitable for clinical or legal purposes. The admissibility of such evidence in legal cases also strongly depends on laws that vary between jurisdictions. For these reasons, the task force concludes that the use of brain imaging findings to support or dispute a claim of chronic pain - effectively as a pain lie detector - is not warranted, but that imaging should be used to further our understanding of the mechanisms underlying pain.
Hah JM, Sturgeon JA, Zocca J, Sharifzadeh Y, Mackey SC. Factors associated with prescription opioid misuse in a cross-sectional cohort of patients with chronic non-cancer pain. J. Pain Res. 2017;10:979-987.
OBJECTIVE: To examine demographic features, psychosocial characteristics, pain-specific behavioral factors, substance abuse history, sleep, and indicators of overall physical function as predictors of opioid misuse in patients presenting for new patient evaluation at a tertiary pain clinic. METHODS: Overall, 625 patients with chronic non-cancer pain prospectively completed the Collaborative Health Outcomes Information Registry, assessing pain catastrophizing, National Institutes of Health Patient-Reported Outcomes Measurement Information System standardized measures (pain intensity, pain behavior, pain interference, physical function, sleep disturbance, sleep-related impairment, anger, depression, anxiety, and fatigue), and substance use history. Additional information regarding current opioid prescriptions and opioid misuse was examined through retrospective chart review. RESULTS: In all, 41 (6.6%) patients presented with some indication of prescription opioid misuse. In the final multivariable logistic regression model, those with a history of illicit drug use (odds ratio [OR] 5.45, 95% confidence interval [CI] 2.48-11.98, p\textless0.0001) and a current opioid prescription (OR 4.06, 95% CI 1.62-10.18, p=0.003) were at elevated risk for opioid misuse. Conversely, every 1-h increase in average hours of nightly sleep decreased the risk of opioid misuse by 20% (OR 0.80, 95% CI 0.66-0.97, p=0.02). CONCLUSION: These findings indicate the importance of considering substance use history, current opioid prescriptions, and sleep in universal screening of patients with chronic non-cancer pain for opioid misuse. Future work should target longitudinal studies to verify the causal relationships between these variables and subsequent opioid misuse.
Harden N, Maihofner C, Abousaad E, et al. A prospective, multisite, international validation of the Complex Regional Pain Syndrome Severity Score. Pain. 2017;158(8):1430-1436.
Clinical diagnosis of complex regional pain syndrome (CRPS) is a dichotomous (yes/no) categorization, a format necessary for clinical decision making. Such dichotomous diagnostic categories do not convey an individual s subtle gradations in the severity of the condition over time and have poor statistical power when used as an outcome measure in research. This prospective, international, multicenter study slightly modified and further evaluated the validity of the CRPS Severity Score (CSS), a continuous index of CRPS severity. Using a prospective design, medical evaluations were conducted in 156 patients with CRPS to compare changes over time in CSS scores between patients initiating a new treatment program and patients on stable treatment regimens. New vs stable categorizations were supported by greater changes in pain and function in the former. Results indicated that CSS values in the stable CRPS treatment group exhibited much less change over time relative to the new treatment group, with intraclass correlations nearly twice as large in the former. A calculated smallest real difference value revealed that a change in the CSS of \$\geq\$4.9 scale points would indicate real differences in CRPS symptomatology (with 95% confidence). Across groups, larger changes in CRPS features on the CSS over time were associated in the expected direction with greater changes in pain intensity, fatigue, social functioning, ability to engage in physical roles, and general well-being. The overall pattern of findings further supports the validity of the CSS as a measure of CRPS severity and suggests it may prove useful in clinical monitoring and outcomes research.