# Publications

## 2020

Falasinnu T, Drenkard C, Bao G, Mackey S, Lim S. The problem of pain in lupus: an explication of the role of biopsychosocial mechanisms. J. Rheumatol. 2020.
OBJECTIVE: To define biopsychosocial mechanisms of pain that go above and beyond disease activity and organ damage in systemic lupus erythematosus (SLE). METHODS: We conducted a cross-sectional analysis of patient-reported data in a population-based registry of 766 people with SLE. Predictors of pain intensity and interference were examined using hierarchical linear regression. We built two main hierarchical regression models: pain intensity regressed on disease activity and organ damage; and pain interference regressed on disease activity and organ damage. For each model, we sought to establish the relationship between pain outcomes and the primary exposures using sequential steps comprising the inclusion of each construct in six stages: demographic, socioeconomic, physical, psychological, behavioral and social factors. We also conducted sensivity analyses eliminating all overt aspects of pain in the disease activity measure and reestimated the models. RESULTS: Disease activity and organ damage explained 32-33% of the variance in pain intensity and interference. Sociodemographic factors accounted for an additional 4-9% of variance in pain outcomes, while psychosocial/behavioral factors accounted for the final 4% of variance. In the sensitivity analyses, we found that disease activity and organ damage explained 25% of the variance in pain outcomes. CONCLUSION: Disease activity only explained 33% of the variance of pain outcomes. However, there was an attenuation in these associations after accounting for psychosocial/behavioral factors, highlighting their roles in modifying the relationship between disease activity and pain. These findings suggest that multilevel interventions may be needed to tackle the negative impact of pain in SLE.
OBJECTIVE: Increased opioid prescription to relieve pain among patients with chronic pain is associated with increased risk for misuse, potentially leading to substance use disorders and overdose death. We aimed to characterize the relative importance and identify the most significant of several potential risk factors for the severity of self-reported prescribed opioid misuse behaviors. METHODS: A sample of 1,193 patients (mean age \$\pm\$ SD = 50.72 \$\pm\$ 14.97 years, 64.04% female) with various chronic pain conditions completed a multidimensional registry assessing four pain severity measures and 14 physical, mental, and social health status factors using the National Institutes of Health s Patient-Reported Outcomes Measurement Information System (PROMIS). A validated PROMIS measure of medication misuse was completed by 692 patients who endorsed currently taking opioid medication. Patients taking opioid medications were compared across all measures with those who do not take opioid medications. Subsequently, a data-driven regression analysis was used to determine which measures best explained variability in severity of misuse. We hypothesized that negative affect-related factors, namely anxiety, anger, and/or depression, would be key predictors of misuse severity due to their crucial role in chronic pain and substance use disorders. RESULTS: Patients taking opioid medications had significantly greater impairment across most measures. Above and beyond demographic variables, the only and most significant predictors of prescribed opioid misuse severity were as follows: anxiety (β = 0.15, P = 0.01), anger (β = 0.13, P = 0.02), Pain Intensity-worst (β = 0.09, P = 0.02), and depression (β = 0.13, P = 0.04). CONCLUSIONS: Findings suggest that anxiety, anger, and depression are key factors associated with prescribed opioid misuse tendencies in patients with chronic pain and that they are potential targets for therapeutic intervention.
Background: Preoperative patient-specific risk factors may elucidate the mechanisms leading to the persistence of pain and opioid use after surgery. This study aimed to determine whether similar or discordant preoperative factors were associated with the duration of postoperative pain and opioid use. Methods: In this post hoc analysis of a randomized, double-blind, placebo-controlled trial of perioperative gabapentin vs active placebo, 410 patients aged 18-75 years, undergoing diverse operations underwent preoperative assessments of pain, opioid use, substance use, and psychosocial variables. After surgery, a modified Brief Pain Inventory was administered over the phone daily up to 3 months, weekly up to 6 months, and monthly up to 2 years after surgery. Pain and opioid cessation were defined as the first of 5 consecutive days of 0 out of 10 pain or no opioid use, respectively. Results: Overall, 36.1%, 19.8%, and 9.5% of patients continued to report pain, and 9.5%, 2.4%, and 1.7% reported continued opioid use at 3, 6, and 12 months after surgery. Preoperative pain at the future surgical site (every 1-point increase in the Numeric Pain Rating Scale; HR 0.93; 95% CI 0.87-1.00; P=0.034), trait anxiety (every 10-point increase in the Trait Anxiety Inventory; HR 0.79; 95% CI 0.68-0.92; P=0.002), and a history of delayed recovery after injury (HR 0.62; 95% CI 0.40-0.96; P=0.034) were associated with delayed pain cessation. Preoperative opioid use (HR 0.60; 95% CI 0.39-0.92; P=0.020), elevated depressive symptoms (every 5-point increase in the Beck Depression Inventory-II score; HR 0.88; 95% CI 0.80-0.98; P=0.017), and preoperative pain outside of the surgical site (HR 0.94; 95% CI 0.89-1.00; P=0.046) were associated with delayed opioid cessation, while perioperative gabapentin promoted opioid cessation (HR 1.37; 95% CI 1.06-1.77; P=0.016). Conclusion: Separate risk factors for prolonged post-surgical pain and opioid use indicate that preoperative risk stratification for each outcome may identify patients needing personalized care to augment universal protocols for perioperative pain management and conservative opioid prescribing to improve long-term outcomes.
OBJECTIVE: Evidence to date, while sparse, suggests that patients taking long-term opioids require special considerations and protections to prevent potential iatrogenic harms from opioid de-prescribing, such as increased pain or suffering. Following this study protocol, the EMPOWER study seeks to address multiple unmet needs of patients with chronic pain who desire to reduce long-term opioid therapy, and provide the clinical evidence on effective methodology. METHODS: EMPOWER applies patient-centered methods for voluntary prescription opioid reduction conducted within a comprehensive, multi-state, 3-arm randomized controlled comparative effectiveness study of three study arms (1) group cognitive behavioral therapy for chronic pain; (2) group chronic pain self-management; and (3) usual care (taper only). Specialized electronic data capture systems collect patient reported symptoms and satisfaction data weekly and monthly during the taper, with real-time clinical alerts and electronic feedback loops informing, documenting, and steering needed care actions. CONCLUSION: The EMPOWER study seeks to provide granular evidence on patient response to voluntary opioid tapering, and will provide evidence to inform clinical systems changes, clinical care, patient satisfaction, and patient outcomes for opioid reduction.
Sturgeon JA, Khan J, Hah JM, et al. Clinical Profiles of Concurrent Cannabis Use in Chronic Pain: A CHOIR Study. Pain Med. 2020;21(11):3172-3179.
OBJECTIVE: Despite evidence of the analgesic benefits of cannabis, there remains a relative scarcity of research on the short- and long-term effects of cannabis use in individuals with chronic pain. DESIGN: The current study is a secondary analysis of clinical data from the Collaborative Health Outcomes Information Registry (CHOIR). SETTING: Data were drawn from a cohort of patients of a multidisciplinary tertiary care pain clinic. SUBJECTS: The study sample consisted of data from 7,026 new patient visits from CHOIR; of these, 1,668 patients with a follow-up time point within 180 days were included in a longitudinal analysis. METHODS: Clinical data were analyzed to characterize cross-sectional differences in pain and indicators of psychological and physical function according to self-reported, concurrent cannabis use. Additionally, a propensity score-weighted longitudinal analysis was conducted, examining cannabis use as a predictor of changes in clinical variables across time. RESULTS: Cross-sectional analyses suggested significantly poorer sleep and significantly higher intensities of pain, emotional distress, and physical and social dysfunction in patients reporting ongoing cannabis use; however, these differences were relatively small in magnitude. However, no differences between cannabis users and nonusers in terms of longitudinal changes in clinical variables were noted. DISCUSSION: Our results are among the first to examine concurrent cannabis use as a prognostic variable regarding trajectories of pain-related variables in tertiary care. Future studies may benefit from examining the effect of cannabis initiation, concurrent medication use, and specific aspects of cannabis use (dose, duration of use, or cannabis type) on clinical outcomes.
Background and aims A sizable body of research has elucidated the significant role of psychological reactions to trauma on pain coping and outcomes. In order to best inform intervention development and clinical care for patients with both trauma and pain at the tertiary care level, greater clarity is needed regarding the magnitude of these effects and the specific pathways through which they may or may not function at the time of first presentation to such a treatment setting. To achieve this, the current study examined the cross-sectional relationships between traumatic etiology of pain, psychological distress (anger, depressive symptoms, and PTSD symptoms), and pain outcomes (pain catastrophizing, physical function, disability status). Methods Using a structural path modeling approach, analyses were conducted using a large sample of individuals with chronic pain (n = 637) seeking new medical evaluation at a tertiary pain management center, using the Collaborative Health Outcomes Information Registry (CHOIR). We hypothesized that the relationships between traumatic etiology of pain and poorer pain outcomes would be mediated by higher levels of psychological distress. Results Our analyses revealed modest relationships between self-reported traumatic etiology of pain and pain catastrophizing, physical function, and disability status. In comparison, there were stronger relationships between indices of psychological distress and pain catastrophizing, but a weaker pattern of associations between psychological distress and physical function and disability measures. Conclusions To the relatively small extent that self-reported traumatic etiology of pain correlates with pain-related outcomes, these relationships appear to be due primarily to the presence of psychiatric symptoms and manifest most notably in the context of psychological responses to pain (i.e. catastrophizing about pain). Implications Findings from this study highlight the need for early intervention for patients with traumatic onset of pain and for clinicians at tertiary pain centers to include more detailed assessments of psychological distress and trauma as a component of comprehensive chronic pain treatment.
Sciences ENA of, Division M, Services B on HC, et al. Temporomandibular Disorders: Priorities for Research and Care. National Academies Press; 2020.
Temporomandibular disorders (TMDs), are a set of more than 30 health disorders associated with both the temporomandibular joints and the muscles and tissues of the jaw. TMDs have a range of causes and often co-occur with a number of overlapping medical conditions, including headaches, fibromyalgia, back pain and irritable bowel syndrome. TMDs can be transient or long-lasting and may be associated with problems that range from an occasional click of the jaw to severe chronic pain involving the entire orofacial region. Everyday activities, including eating and talking, are often difficult for people with TMDs, and many of them suffer with severe chronic pain due to this condition. Common social activities that most people take for granted, such as smiling, laughing, and kissing, can become unbearable. This dysfunction and pain, and its associated suffering, take a terrible toll on affected individuals, their families, and their friends. Individuals with TMDs often feel stigmatized and invalidated in their experiences by their family, friends, and, often, the health care community. Misjudgments and a failure to understand the nature and depths of TMDs can have severe consequences - more pain and more suffering - for individuals, their families and our society. Temporomandibular Disorders: Priorities for Research and Care calls on a number of stakeholders - across medicine, dentistry, and other fields - to improve the health and well-being of individuals with a TMD. This report addresses the current state of knowledge regarding TMD research, education and training, safety and efficacy of clinical treatments of TMDs, and burden and costs associated with TMDs. The recommendations of Temporomandibular Disorders focus on the actions that many organizations and agencies should take to improve TMD research and care and improve the overall health and well-being of individuals with a TMD.
Gilam G, Gross JJ, Wager TD, Keefe FJ, Mackey SC. What Is the Relationship between Pain and Emotion? Bridging Constructs and Communities. Neuron. 2020;107(1):17-21.
Although pain is defined as a sensory and emotional experience, it is traditionally researched and clinically treated separately from emotion. Conceptual and mechanistic relationships between these constructs highlight the need for better understanding of their bi-directional influences and the value of bridging the pain and emotion research and clinical communities.