# PUBLICATIONS

## 2019

OBJECTIVE: The National Institutes of Health s Patient-Reported Outcomes Measurement Information System (PROMIS)® includes an item bank for measuring misuse of prescription pain medication (PROMIS-Rx Misuse). The bank was developed and its validity evaluated in samples of community-dwelling adults and patients in addiction treatment programs. The goal of the current study was to investigate the validity of the item bank among patients with mixed-etiology chronic pain conditions. METHOD: A consecutive sample of 288 patients who presented for initial medical evaluations at a tertiary pain clinic completed questionnaires using the open-source Collaborative Health Outcomes Information Registry. Participants were predominantly middle-aged (M [SD] = 51.6 [15.5] years), female (62.2%), and white/non-Hispanic (51.7%). Validity was evaluated by estimating the association between PROMIS-Rx Misuse scores and scores on other measures and testing the ability of scores to distinguish among risk factor subgroups expected to have different levels of prescription pain medicine misuse (known groups analyses). RESULTS: Overall, score associations with other measures were as expected and scores effectively distinguished among patients with and without relevant risk factors. CONCLUSION: The study results supported the preliminary validity of PROMIS-Rx Misuse item bank scores for the assessment of prescription opioid misuse in patients visiting an outpatient pain clinic.
Karayannis N, Baumann I, Sturgeon JA, Melloh M, Mackey SC. The Impact of Social Isolation on Pain Interference: A Longitudinal Study. Ann. Behav. Med. 2019;53(1):65-74.
Background: Evidence suggests social interactions play an important role in pain perception. Purpose: The aim of this study was to determine whether social isolation (SI) in people with persistent pain determines pain interference (PI) and physical function over time. Methods: Patients seeking care at a tertiary pain management referral center were administered the Patient Reported Outcome Measurement Information System (PROMIS®) SI, PI, physical function, depression, and average pain intensity item banks at their initial consultation and subsequent visits as part of their routine clinical care. We used a post hoc simulation of an experiment using propensity score matching (n = 4,950) and carried out a cross-lagged longitudinal analysis (n = 312) of retrospective observational data. Results: Cross-lagged longitudinal analysis showed that SI predicted PI at the next time point, above and beyond the effects of pain intensity and covariates, but not vice versa. Conclusions: These data support the importance of SI as a factor in pain-related appraisal and coping and demonstrate that a comprehensive assessment of the individuals social context can provide a better understanding of the differential trajectories for a person living with pain. Our study provides evidence that the impact of pain is reduced in individuals who perceive a greater sense of inclusion from and engagement with others. This study enhances the understanding of how social factors affect pain and have implications for how the effectiveness of therapeutic interventions may be improved. Therapeutic interventions aimed at increasing social connection hold merit in reducing the impact of pain on engagement with activities.

## 2018

Martucci KT, Borg N, MacNiven KH, Knutson B, Mackey SC. Altered prefrontal correlates of monetary anticipation and outcome in chronic pain. Pain. 2018;159(8):1494-1507.
Chronic pain may alter both affect- and value-related behaviors, which represents a potentially treatable aspect of chronic pain experience. Current understanding of how chronic pain influences the function of brain reward systems, however, is limited. Using a monetary incentive delay task and functional magnetic resonance imaging (fMRI), we measured neural correlates of reward anticipation and outcomes in female participants with the chronic pain condition of fibromyalgia (N = 17) and age-matched, pain-free, female controls (N = 15). We hypothesized that patients would demonstrate lower positive arousal, as well as altered reward anticipation and outcome activity within corticostriatal circuits implicated in reward processing. Patients demonstrated lower arousal ratings as compared with controls, but no group differences were observed for valence, positive arousal, or negative arousal ratings. Group fMRI analyses were conducted to determine predetermined region of interest, nucleus accumbens (NAcc) and medial prefrontal cortex (mPFC), responses to potential gains, potential losses, reward outcomes, and punishment outcomes. Compared with controls, patients demonstrated similar, although slightly reduced, NAcc activity during gain anticipation. Conversely, patients demonstrated dramatically reduced mPFC activity during gain anticipation-possibly related to lower estimated reward probabilities. Further, patients demonstrated normal mPFC activity to reward outcomes, but dramatically heightened mPFC activity to no-loss (nonpunishment) outcomes. In parallel to NAcc and mPFC responses, patients demonstrated slightly reduced activity during reward anticipation in other brain regions, which included the ventral tegmental area, anterior cingulate cortex, and anterior insular cortex. Together, these results implicate altered corticostriatal processing of monetary rewards in chronic pain.
Neuroimaging research has demonstrated definitive involvement of the central nervous system in the development, maintenance, and experience of chronic pain. Structural and functional neuroimaging has helped elucidate central nervous system contributors to chronic pain in humans. Neuroimaging of pain has provided a tool for increasing our understanding of how pharmacologic and psychologic therapies improve chronic pain. To date, findings from neuroimaging pain research have benefitted clinical practice by providing clinicians with an educational framework to discuss the biopsychosocial nature of pain with patients. Future advances in neuroimaging-based therapeutics (e.g., transcranial magnetic stimulation, real-time functional magnetic resonance imaging neurofeedback) may provide additional benefits for clinical practice. In the future, with standardization and validation, brain imaging could provide objective biomarkers of chronic pain, and guide treatment for personalized pain management. Similarly, brain-based biomarkers may provide an additional predictor of perioperative prognoses.
Sturgeon JA, Hah JM, Sharifzadeh Y, et al. Predictors of Daily Pain Medication Use in Individuals with Recurrent Back Pain. Int. J. Behav. Med. 2018;25(2):252-258.
PURPOSE: A key component to chronic pain management regimens is the use of analgesic medications. Psychological factors, such as mood states, may also affect the use of pain medications for individuals with chronic pain, but few observational studies have examined how these factors may predict pain medication use at the daily level. METHODS: Daily assessments from 104 individuals with back pain were used to examine fluctuations in daily pain intensity, mood, sleep quality, and physical activity as predictors of the likelihood of pain medication (opioid and non-opioid) use and levels of medication use on the same day. RESULTS: Pain intensity and mood ratings significantly predicted whether participants used pain medication on the same day, while only pain intensity predicted whether participants used more medication than usual. Further, current opioid users were more likely to increase the amount of their medication use on days of higher pain. DISCUSSION: This article identifies fluctuations in daily pain intensity and mood as salient predictors of daily pain medication use in individuals with recurrent back pain. The current study is among the first to highlight both pain and mood states as predictors of daily pain medication use in individuals with back pain, though future studies may expand on these findings through the use of higher-resolution daily medication use variables.
Sutcliffe S, Jemielita T, Lai H, et al. A Case-Crossover Study of Urological Chronic Pelvic Pain Syndrome Flare Triggers in the MAPP Research Network. J. Urol. 2018;199(5):1245-1251.
PURPOSE: Although many factors have been proposed to trigger symptom exacerbations (flares) in patients with interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, few studies have investigated these factors empirically. Therefore, we embedded a case-crossover study in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain longitudinal study to evaluate a range of patient reported triggers. MATERIALS AND METHODS: We assessed exposure to proposed triggers, including diet, physical activities, sedentary behaviors, stress, sexual activities, infection-like symptoms and allergies, by questionnaire a maximum of 3 times when participants reported flares and at 3 randomly selected times. We compared participant preflare to nonflare exposures by conditional logistic regression. RESULTS: In our full analytical sample of 292 participants only 2 factors, including recent sexual activity (OR 1.44, 95% CI 1.06-1.96) and urinary tract infection symptoms (OR 3.39, 95% CI 2.02-5.68), which may overlap with those of flares, were associated with flare onset. On subanalyses restricted to flares with specific suspected triggers additional positive associations were observed for some factors such as certain dietary factors, abdominal muscle exercises, and vaginal infection-like symptoms and fever, but not for other factors (eg stress). CONCLUSIONS: Except for sexual activity our findings suggest that patient reported triggers may be individual or group specific, or they may not contribute to flares. These findings suggest caution in following rigid, global flare prevention strategies and support additional research to develop evidence-based strategies.
OBJECTIVE: Perceived injustice (PI) has been identified as an important risk factor for pain-related outcomes. To date, research has shown that pain acceptance and anger are mediators of the association between PI and pain-related outcomes. However, a combined conceptual model that addresses the interrelationships between these variables is currently lacking. Therefore, the current study aimed to examine the potential mediating roles of pain acceptance and anger on the association between PI and adverse pain-related outcomes (physical function, pain intensity, opioid use status). MATERIALS AND METHOD: This cross-sectional study used a sample of 354 patients with chronic pain being treated at a tertiary pain treatment center. Participants completed measures of PI, pain acceptance, anger, physical function, pain intensity, and opioid use status. Mediation analyses were used to examine the impact of pain acceptance and anger on the association between PI and pain-related outcomes. RESULTS: Examination of the specific indirect effects revealed that pain acceptance fully mediated the relationship between PI and physical function, as well as the relationship between PI and opioid use status. Pain acceptance emerged as a partial mediator of the relationship between PI and pain intensity. DISCUSSION: This is the first study to provide a combined conceptual model investigating the mediating roles of pain acceptance and anger on the relationship between PI and pain outcomes. On the basis of our findings, low levels of pain acceptance associated with PI may help explain the association between PI and adverse pain outcomes. Clinical and theoretical implications are discussed.
BACKGROUND: The Institute of Medicine (IOM) reported that chronic pain affects about 100 million U.S. adults, with chronic low back pain (CLBP) cited as the most prevalent type. Pain catastrophizing is a psychological construct shown to predict the development and trajectory of chronic pain and patient response to pain treatments. While effective treatment for pain catastrophizing typically includes eight-session groups of cognitive behavioral therapy (CBT), a single-session targeted treatment class yielded promising results which, if replicated and extended, could prove to efficiently and cost-effectively reduce pain catastrophizing. In this trial, we seek to determine the comparative efficacy of this novel single-session pain catastrophizing class to an eight-session course of pain CBT and a single-session back pain health education class. We will also explore the psychosocial mechanisms and outcomes of pain catastrophizing treatment. METHODS: In this trial we will randomize 231 individuals with CLBP to one of three treatment arms: (1) pain-CBT (eight weekly 2-h group sessions with home exercises and readings); (2) a single 2-h pain catastrophizing class; or (3) a single 2-h back pain health education class (active control). For the primary outcome of pain catastrophizing, the trial is designed as a non-inferiority test between pain-CBT and the single-session pain catastrophizing class, and as a superiority test between the single-session pain catastrophizing class and the health education class. Team researchers masked to treatment assignment will assess outcomes up to six months post treatment. DISCUSSION: If the single-session targeted pain catastrophizing class is found to be an effective treatment for patients with CLBP, this low cost and low burden treatment could dismantle many of the current barriers and burdens of effective pain care. Further, elucidation of the mechanisms of pain catastrophizing treatments will facilitate future research on the topic as well as further development and refinement of treatments. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03167086 . Registered on 22 May 2017.
INTRODUCTION: Complex Regional Pain Syndrome (CRPS), a rare and severe chronic pain condition, often responds poorly to existing treatments. Previous studies demonstrated Transcranial Magnetic Stimulation (TMS) provided short-term pain relief for upper extremity CRPS. METHODS: Building on previous methodologies, we employed a TMS protocol that may lead to significant pain relief for upper and lower extremity CRPS in a nonrandomized open label pilot trial involving 21 participants. We individualized TMS coil positioning over motor cortex of somatic pain location, and administered intermittent theta-burst stimulation followed by 10 Hz high-frequency stimulation using a deeper targeting coil. We assessed response (\$\geq\$30% pain reduction) from a single session (n = 5) and five consecutive daily sessions (n = 12) and compared change in pain from baseline, after one treatment and one-week posttreatment between groups using a mixed ANVOA. RESULTS: Both groups demonstrated significant pain reduction after one session and one-week posttreatment; however, no group differences were present. From a single session, 60% of participants responded at Week 1. From five sessions, 58% and 50% of participants responded at Weeks 1 and 2, respectively. Two from each group achieved \textgreater50% pain reduction beyond six to eight weeks. No serious adverse events occurred. Though headache and nausea were the most common side-effects, we urge careful monitoring to prevent seizures with this protocol. CONCLUSIONS: We used a TMS protocol that, for the first time, led to significant pain relief in upper and lower extremity CRPS, and will soon examine our protocol in a larger, controlled trial.
Background: “The ongoing opioid crisis lies at the intersection of two substantial public health challenges-reducing the burden of suffering from pain and containing the rising toll of the harms that can result from the use of opioid medications” [1]. Improved pain education for health care providers is an essential component of the multidimensional response to both still-unmet challenges [2,3]. Despite the importance of licensing examinations in assuring competency in health care providers, there has been no prior appraisal of pain and related content within the United States Medical Licensing Examination (USMLE). Methods: An expert panel developed a novel methodology for characterizing USMLE questions based on pain core competencies and topical and public health relevance. Results: Under secure conditions, raters used this methodology to score 1,506 questions, with 28.7% (432) identified as including the word “pain.” Of these, 232 questions (15.4% of the 1,506 USMLE questions reviewed) were assessed as being fully or partially related to pain, rather than just mentioning pain but not testing knowledge of its mechanisms and their implications for treatment. The large majority of questions related to pain (88%) focused on assessment rather than safe and effective pain management, or the context of pain. Conclusions: This emphasis on assessment misses other important aspects of safe and effective pain management, including those specific to opioid safety. Our findings inform ways to improve the long-term education of our medical and other graduates, thereby improving the health care of the populations they serve.