Age, Race, Ethnicity, and Sex of Participants in Clinical Trials Focused on Chronic Pain.

There is limited data on equitable inclusion in chronic pain trials. We aimed to 1) identify the frequency of reporting age, race, ethnicity, and sex in clinical trials targeting chronic pain, and 2) compare sociodemographic representation to the United States (US) population. We examined US-based intervention trials for chronic pain initiated between 2007 and 2021 and registered on ClinicalTrials.gov. We 1) assessed the frequency of reporting each demographic variable, 2) compared representation with US population estimates, and 3) explored change in reporting over time. Of 501 clinical trials, the frequency of reporting was as follows: 36.9% reported older adults, 54.3% reported race, 37.4% reported ethnicity, and 100% reported sex. Rates of race and ethnicity reporting increased, but older adult age reporting decreased over time (ps < .00001). Compared to 2020 US population estimates, there was an equitable representation of older adults, under-representation of individuals identifying as American Indian or Alaska Native (.8% vs .6%), Asian (5.6% vs 2.9%), Black or African American (12.6% vs 12.2%), with more than one race (2.9% vs 1.2%), and Hispanic/Latino (16.9% vs 14.1%). There was an over-representation of individuals identifying as Native Hawaiian or Pacific Islander (.2% vs .5%) or White (70.4% vs 72.9%), and of females (50.8% vs 68.4%). Some representation rates varied by chronic pain condition. Reporting of older adult age, race, and ethnicity was low in chronic pain trials in ClinicalTrials.gov, reinforcing the need for adhering to reporting guidelines. Representation varied across trials compared with US population data, particularly among those identifying as Hispanic/Latino and certain minority racial groups. PERSPECTIVE: Despite initiatives to increase the reporting of demographic information, doing so in clinical pain trials is far from ubiquitous. Moreover, efforts to improve diversity in these trials continue to be insufficient. Indeed, Black, Indigenous, and People of Color (BIPOC) remain under-represented in clinical pain trials.

Pain coping, multidisciplinary care, and mHealth: Patients' views on managing advanced cancer pain.

OBJECTIVE: Pain is common among people with advanced cancer. While opioids provide significant relief, incorporating psycho-behavioral treatments may improve pain outcomes. We examined patients' experiences with pain self-management and how their self-management of chronic, cancer-related pain may be complemented by behavioral mobile health (mHealth) interventions. METHODS: We conducted semi-structured qualitative interviews with patients with advanced cancer and pain. Each participant reviewed content from our behavioral mHealth application for cancer pain management and early images of its interface. Participants reflected on their experiences self-managing cancer pain and on app content. Interviews were transcribed verbatim and analyzed using a combination of inductive and deductive thematic analysis. RESULTS: Patients (n = 28; 54% female; mean age = 53) across two geographic regions reported using psychological strategies (e.g., reframing negative thoughts, distraction, pain acceptance, social support) to manage chronic cancer-related pain. Patients shared their perspectives on the integration of psycho-behavioral pain treatments into their existing medical care and their experiences with opioid hesitancy. Patient recommendations for how mHealth interventions could best support them coalesced around two topics: 1.) convenience in accessing integrated pharmacological and psycho-behavioral pain education and communication tools and 2.) relevance of the specific content to their clinical situation. CONCLUSIONS: Integrated pharmacological and psycho-behavioral pain treatments were important to participants. This underscores a need to coordinate complimentary approaches when developing cancer pain management interventions. Participant feedback suggests that an mHealth intervention that integrates pain treatments may have the capacity to increase advanced cancer patients' access to destigmatizing, accessible care while improving pain self-management.

Brief Assessment of Patient Phenotype to Explain Variability in Postsurgical Pain and Opioid Consumption after Cesarean Delivery: Performance of a Novel Brief Questionnaire Compared to Long Questionnaires.

BACKGROUND: Understanding factors that explain why some women experience greater postoperative pain and consume more opioids after cesarean delivery is crucial to building an evidence base for personalized prevention. Comprehensive psychosocial assessment with validated questionnaires in the preoperative period can be time-consuming. A three-item questionnaire has shown promise as a simpler tool to be integrated into clinical practice, but its brevity may limit the ability to explain heterogeneity in psychosocial pain modulators among individuals. This study compared the explanatory ability of three models: (1) the 3-item questionnaire, (2) a 58-item questionnaire (long) including validated questionnaires (e.g., Brief Pain Inventory, Patient Reported Outcome Measurement Information System [PROMIS]) plus the 3-item questionnaire, and (3) a novel 19-item questionnaire (brief) assessing several psychosocial factors plus the 3-item questionnaire. Additionally, this study explored the utility of adding a pragmatic quantitative sensory test to models. METHODS: In this prospective, observational study, 545 women undergoing cesarean delivery completed questionnaires presurgery. Pain during local anesthetic skin wheal before spinal placement served as a pragmatic quantitative sensory test. Postoperatively, pain and opioid consumption were assessed. Linear regression analysis assessed model fit and the association of model items with pain and opioid consumption during the 48 h after surgery. RESULTS: A modest amount of variability was explained by each of the three models for postoperative pain and opioid consumption. Both the brief and long questionnaire models performed better than the three-item questionnaire but were themselves statistically indistinguishable. Items that were independently associated with pain and opioid consumption included anticipated postsurgical pain medication requirement, surgical anxiety, poor sleep, pre-existing pain, and catastrophic thinking about pain. The quantitative sensory test was itself independently associated with pain across models but only modestly improved models for postoperative pain. CONCLUSIONS: The brief questionnaire may be more clinically feasible than longer validated questionnaires, while still performing better and integrating a more comprehensive psychosocial assessment than the three-item questionnaire.

The role of sleep disturbance in reduced accuracy on a divided attention task among patients with fibromyalgia.

Introduction: Patients with fibromyalgia show impaired cognitive performance compared with healthy, pain-free controls. Sleep disturbance, anxiety, and depression are highly prevalent among patients with fibromyalgia, and each is associated with impaired cognitive performance. Yet, limited work has explored whether psychosocial factors contribute to group differences in cognitive performance. Objectives: This secondary data analysis investigated differences in cognitive performance between patients with fibromyalgia and healthy controls, and whether psychosocial factors accounted for these differences. Methods: Adults with fibromyalgia (N = 24) and healthy, pain-free controls (N = 26) completed 2 cognitive tasks and the Patient-Reported Outcomes Measurement Information System sleep disturbance, anxiety, and depression short forms. Independent samples t tests were used to test for differences in cognitive performance between patients with fibromyalgia and healthy controls. Pearson correlations were conducted to examine associations between psychosocial factors and cognitive performance. Psychosocial factors significantly related to cognitive performance were explored as potential mediators of group differences in cognitive performance. Results: Patients with fibromyalgia demonstrated poorer accuracy for divided attention compared with healthy controls, and sleep disturbance mediated this group difference. On the attentional switching task, healthy controls showed a greater switch-cost for accuracy compared with patients with fibromyalgia, but there was no group difference in reaction time. Anxiety and depression were not related to cognitive performance. Conclusion: We found that patients with fibromyalgia reported greater sleep disturbance and, in turn, had poorer accuracy on the divided attention task. Sleep disturbance is modifiable with behavioral interventions, such as cognitive behavioral therapy, and may be a target for improving sleep quality and cognitive performance among patients with fibromyalgia.

Optimizing the use of ketamine to reduce chronic postsurgical pain in women undergoing mastectomy for oncologic indication: study protocol for the KALPAS multicenter randomized controlled trial.

BACKGROUND: Mastectomies are commonly performed and strongly associated with chronic postsurgical pain (CPSP), more specifically termed postmastectomy pain syndrome (PMPS), with 25-60% of patients reporting pain 3 months after surgery. PMPS interferes with function, recovery, and compliance with adjuvant therapy. Importantly, it is associated with chronic opioid use, as a recent study showed that 1 in 10 patients continue to use opioids at least 3 months after curative surgery. The majority of PMPS patients are women, and, over the past 10 years, women have outpaced men in the rate of growth in opioid dependence. Standard perioperative multimodal analgesia is only modestly effective in prevention of CPSP. Thus, interventions to reduce CPSP and PMPS are urgently needed. Ketamine is well known to improve pain and reduce opioid use in the acute postoperative period. Additionally, ketamine has been shown to control mood in studies of anxiety and depression. By targeting acute pain and improving mood in the perioperative period, ketamine may be able to prevent the development of CPSP. METHODS: Ketamine analgesia for long-lasting pain relief after surgery (KALPAS) is a phase 3, multicenter, randomized, placebo-controlled, double-blind trial to study the effectiveness of ketamine in reducing PMPS. The study compares continuous perioperative ketamine infusion vs single-dose ketamine in the postanesthesia care unit vs placebo for reducing PMPS. Participants are followed for 1 year after surgery. The primary outcome is pain at the surgical site at 3 months after the index surgery as assessed with the Brief Pain Inventory-short form pain severity subscale. DISCUSSION: This project is part of the NIH Helping to End Addiction Long-term (HEAL) Initiative, a nationwide effort to address the opioid public health crisis. This study can substantially impact perioperative pain management and can contribute significantly to combatting the opioid epidemic. TRIAL REGISTRATION: ClinicalTrials.gov NCT05037123. Registered on September 8, 2021.

Development and pre-pilot testing of STAMP + CBT: an mHealth app combining pain cognitive behavioral therapy and opioid support for patients with advanced cancer and pain.

PURPOSE: We developed and piloted a mobile health app to deliver cognitive behavioral therapy for pain (pain-CBT), remote symptom monitoring, and pharmacologic support for patients with pain from advanced cancer. METHODS: Using an iterative process of patient review and feedback, we developed the STAMP + CBT app. The app delivers brief daily lessons from pain-CBT and pain psychoeducation, adapted for advanced cancer. Daily surveys assess physical symptoms, psychological symptoms, opioid utilization and relief. Just-in-time adaptive interventions generate tailored psychoeducation in response. We then conducted a single-arm pilot feasibility study at two cancer centers. Patients with advanced cancer and chronic pain used the app for 2 or 4 weeks, rated its acceptability and provided feedback in semi-structured interviews. Feasibility and acceptability were defined as ≥ 70% of participants completing ≥ 50% of daily surveys, and ≥ 80% of acceptability items rated ≥ 4/5. RESULTS: Fifteen participants (female = 9; mean age = 50.3) tested the app. We exceeded our feasibility and accessibility benchmarks: 73% of patients completed ≥ 50% of daily surveys; 87% of acceptability items were rated ≥ 4/5. Participants valued the app's brevity, clarity, and salience, and found education on stress and pain to be most helpful. The app helped participants learn pain management strategies and decrease maladaptive thoughts. However, participants disliked the notification structure (single prompt with one snooze), which led to missed content. CONCLUSION: The STAMP + CBT app was an acceptable and feasible method to deliver psychological/behavioral treatment with pharmacologic support for cancer pain. The app is being refined and will be tested in a larger randomized pilot study. TRN: NCT05403801 (05/06/2022).

A secondary analysis: the impact of pre-existing chronic pain among patients with cancer presenting to the emergency department with acute pain.

PURPOSE: Patients with cancer may experience pain from cancer itself or its treatment. Additionally, chronic pain (CP) predating a patient's cancer diagnosis may make the etiology of pain less clear and the management of pain more complex. In this brief report, we investigated differences in biopsychosocial characteristics, pain severity, and opioid consumption, comparing groups of cancer patients with and without a history of CP who presented to the emergency department (ED) with a complaint of cancer-related pain. METHODS: This secondary analysis of a prospective cohort study included patients with cancer who presented to the ED with a complaint of pain (≥ 4/10). Sociodemographic, clinical, psychological, and pain characteristics were assessed in the ED and subsequent hospitalization. Mann-Whitney U-, T-, and Chi-square tests were used to compare differences between patients with and without pre-existing CP before cancer. RESULTS: Patients with pre-existing CP had lower income (p = 0.21) and less formal education (p = 0.25) and were more likely to have a diagnosis of depression or substance use disorder (p < 0.01). Patients with pre-existing CP reported significantly greater pain severity in the ED and during hospitalization compared to those without pre-existing CP (p < 0.05), despite receiving greater amounts of opioid analgesics (p = 0.036). CONCLUSION: Identifying a history of pre-existing CP during intake may help identify patients with cancer with difficult to manage pain, who may particularly benefit from multimodal interventions and supportive care. In addition, referral of these patients for the management of co-occurring pain disorders may help decrease the usage of the ED for undertreated pain.

Individuals with fibromyalgia report greater pain sensitivity than healthy adults while listening to their favorite music: the contribution of negative affect.

OBJECTIVE: We investigated the impact of favorite music on pain processing among individuals with fibromyalgia. We also examined differences in pain processing between individuals with fibromyalgia and healthy controls (HC) while listening to favorite music and explored whether psychosocial factors contributed to these differences. METHODS: Individuals with fibromyalgia and HC completed baseline psychosocial questionnaires and then underwent quantitative sensory testing (QST) during 3 randomized music conditions (meditative music, favorite music, white noise). Among individuals with fibromyalgia, Friedman tests were used to investigate differences in QST across conditions. Analyses of Covariance were used to examine group (HC vs fibromyalgia) differences in QST during favorite music. Correlations were conducted to explore associations of baseline psychosocial factors with QST during favorite music. Mediation analyses were conducted to explore whether psychosocial factors contributed to greater pain sensitivity among individuals with fibromyalgia compared to HC during favorite music. RESULTS: Individuals with fibromyalgia were less sensitive to pressure pain while listening to their favorite music compared to white noise. Compared to HC, individuals with fibromyalgia reported higher baseline negative affect and lower pain thresholds and tolerances during favorite music. Negative affect partially mediated the relationship between pain status (HC vs fibromyalgia) and pain sensitivity during favorite music. CONCLUSIONS: Individuals with fibromyalgia were less pain sensitive while listening to favorite music than white noise, although they were more sensitive than HC. Greater negative affect endorsed by individuals with fibromyalgia contributed to their greater pain sensitivity. Future studies should explore the impact of favorite music on clinical pain. CLINICAL TRAILS REGISTRATION: This study was registered with ClinicalTrials.gov (NCT04087564) and began on 6/13/2019.

A Randomized Controlled Neuroimaging Trial of Cognitive Behavioral Therapy for Fibromyalgia Pain.

OBJECTIVE: Fibromyalgia (FM) is characterized by pervasive pain-related symptomatology and high levels of negative affect. Mind-body treatments such as cognitive behavioral therapy (CBT) appear to foster improvement in FM via reductions in pain-related catastrophizing, a set of negative, pain-amplifying cognitive and emotional processes. However, the neural underpinnings of CBT's catastrophizing-reducing effects remain uncertain. This randomized controlled mechanistic trial was designed to assess CBT's effects on pain catastrophizing and its underlying brain circuitry. METHODS: Of 114 enrolled participants, 98 underwent a baseline neuroimaging assessment and were randomized to 8 weeks of individual CBT or a matched FM education control (EDU) condition. RESULTS: Compared with EDU, CBT produced larger decreases in pain catastrophizing post treatment (P < 0.05) and larger reductions in pain interference and symptom impact. Decreases in pain catastrophizing played a significant role in mediating those functional improvements in the CBT group. At baseline, brain functional connectivity between the ventral posterior cingulate cortex (vPCC), a key node of the default mode network (DMN), and somatomotor and salience network regions was increased during catastrophizing thoughts. Following CBT, vPCC connectivity to somatomotor and salience network areas was reduced. CONCLUSION: Our results suggest clinically important and CBT-specific associations between somatosensory/motor- and salience-processing brain regions and the DMN in chronic pain. These patterns of connectivity may contribute to individual differences (and treatment-related changes) in somatic self-awareness. CBT appears to provide clinical benefits at least partially by reducing pain-related catastrophizing and producing adaptive alterations in DMN functional connectivity.

Does the Association Between Psychosocial Factors and Opioid Use After Elective Spine Surgery Differ by Sex in Older Adults?

Purpose: Psychosocial disorders have been linked to chronic postoperative opioid use and the development of postoperative pain. The potential interaction between sex and psychosocial factors with respect to opioid use after elective spine surgery in the elderly has not yet been evaluated. Our aim was to assess whether any observed association of anxiety or depression indicators with opioid consumption in the first 72 hours after elective spine surgery varies by sex in adults ≥65 years. Patients and Methods: Secondary analysis of a retrospective cohort of 647 elective spine surgeries performed at Brigham and Women's Hospital, July 1, 2015-March 15, 2017, in patients ≥65. Linear mixed-effects models were used to test whether history of anxiety, anxiolytic use, history of depression, and antidepressant use were associated with opioid consumption 0-24, 24-48, and 48-72 post surgery, and whether these potential associations differed by sex. Results: History of anxiety, anxiolytic use, history of depression, and antidepressant use were more common among women (51.3% of the sample). During the first 24 hours after surgery, men with a preoperative history of anxiety consumed an adjusted mean of 19.5 morphine milligram equivalents (MME) (99.6% CI: 8.1, 31.0) more than men without a history of anxiety; women with a history of anxiety only consumed an adjusted mean 2.9 MME (99.6% CI: -3.1, 8.9) more than women without a history of anxiety (P value for interaction between sex and history of anxiety <0.001). No other interactions were detected between sex and psychosocial factors with respect to opioid use after surgery. Conclusion: Secondary analysis of this retrospective cohort study found minimal evidence that the association between psychosocial factors and opioid consumption after elective spine surgery differs by sex in adults ≥65.

Presurgical sleep and pain behaviors predict insomnia symptoms and pain after total knee arthroplasty: a 12-month longitudinal, observational study.

OBJECTIVE: Up to 40% of individuals who undergo total knee arthroplasty (TKA) experience some degree of pain following surgery. Presurgical insomnia has been identified as a predictor of postsurgical pain; however, modifiable presurgical behaviors related to insomnia have received minimal attention. The objective of the present study was to develop a 2-item sleep and pain behavior scale (SP2) to investigate a maladaptive sleep and pain behavior and is a secondary analysis of a larger, parent study. METHODS: Patients (N = 109) completed SP2 at baseline and 12 months and questionnaires assessing sleep and pain at baseline (pre-TKA), 6 weeks, 3, 6, and 12 months post-TKA. SP2 demonstrated adequate preliminary psychometric properties. RESULTS: As hypothesized, even after controlling for baseline insomnia, pain, anxiety and other covariates, baseline SP2 predicted insomnia symptom severity at 6 weeks (ß = 2.828), 3 (ß = 2.140), 6 (ß = 2.962), and 12 months (ß = 1.835) and pain at 6 weeks (ß = 6.722), 3 (ß = 5.536), and 6 months (ß = 7.677) post-TKA (P < .05). Insomnia symptoms at 6-weeks post-TKA mediated the effect of presurgical SP2 on pain at 3 (95% CI: 0.024-7.054), 6 (95%CI: 0.495-5.243), and 12 months (95% CI: 0.077-2.684). CONCLUSIONS: This provides preliminary evidence that patients who cope with pain by retiring to their bed and bedroom have higher rates of post-surgical insomnia and pain and supports efforts to target this maladaptive sleep and pain behavior to reduce postsurgical pain.

Perioperative insomnia trajectories and functional outcomes after total knee arthroplasty.

ABSTRACT: Longitudinal total knee arthroplasty (TKA) studies indicate that a substantial percentage of patients continue to experience clinically significant pain and functional impairment after surgery. Insomnia has been associated with poorer surgical outcomes; however, previous work has largely focused on long-term postsurgical insomnia. This study builds on previous work by examining sleep and pain outcomes about perioperative insomnia trajectories. Insomnia symptoms (using the Insomnia Severity Index) during the acute perioperative period (2 weeks pre-TKA to 6 weeks post-TKA) were used to classify participants into perioperative insomnia trajectories: (1) No Insomnia (ISI < 8), (2) New Insomnia (baseline < 8; postoperative ≥ 8 or ≥6-point increase), (3) Improved Insomnia (baseline ≥ 8, postoperative < 8 or ≥6-point decrease), and (4) Persistent Insomnia (ISI ≥ 8). Insomnia, pain, and physical functioning were assessed in participants with knee osteoarthritis (n = 173; M age = 65 ± 8.3, 57.8% female) at 5 time points: 2 weeks pre-TKA, post-TKA: 6 weeks, 3 months, 6 months, and 12 months. Significant main effects were seen for insomnia trajectory and time, and trajectory-by-time interactions for postoperative insomnia, pain severity, and physical functioning ( P' s < 0.05). The Persistent Insomnia trajectory had the worst postoperative pain at all follow-ups and marked insomnia and physical functioning impairment post-TKA ( P' s < 0.05). The New Insomnia trajectory had notable long-term insomnia (6 weeks to 6 months) and acute (6 weeks) postoperative pain and physical functioning ( P' s < 0.05). Findings indicated a significant relationship between perioperative insomnia trajectory and postoperative outcomes. Results of this study suggest that targeting presurgical insomnia and preventing the development of acute postoperative insomnia may improve long-term postoperative outcomes, with an emphasis on persistent perioperative insomnia due to poorer associated outcomes.

Let's Get Physical! A Comprehensive Review of Pre- and Post-Surgical Interventions Targeting Physical Activity to Improve Pain and Functional Outcomes in Spine Surgery Patients.

The goal of this comprehensive review was to synthesize the recent literature on the efficacy of perioperative interventions targeting physical activity to improve pain and functional outcomes in spine surgery patients. Overall, research in this area does not yet permit definitive conclusions. Some evidence suggests that post-surgical interventions may yield more robust long-term outcomes than preoperative interventions, including large effect sizes for disability reduction, although there are no studies directly comparing these surgical approaches. Integrated treatment approaches that include psychosocial intervention components may supplement exercise programs by addressing fear avoidance behaviors that interfere with engagement in activity, thereby maximizing the short- and long-term benefits of exercise. Efforts should be made to test brief, efficient programs that maximize accessibility for surgical patients. Future work in this area should include both subjective and objective indices of physical activity as well as investigating both acute postoperative outcomes and long-term outcomes.

Feasibility and reliability of a quantitative sensory testing protocol in youth with acute musculoskeletal pain postsurgery or postinjury.

ABSTRACT: Quantitative sensory testing (QST) is increasingly used in pediatric chronic pain; however, assessment in youth with acute musculoskeletal (MSK) pain is limited. This study evaluated the feasibility, reliability, and sources of variability of a brief QST protocol in 2 clinical samples of youth with acute MSK pain. Participants were 277 youth (M age = 14.5 years, SD = 2.0, range = 11-18 years, 59% female, 81% non-Hispanic) across 3 geographic study sites who completed a QST protocol assessing pressure and thermal pain sensitivity, temporal summation of pain, and conditioned pain modulation 8 weeks after MSK surgery (n = 100) or within 4 weeks after an acute MSK injury (n = 177). High feasibility was demonstrated by protocol completion rates ranging from 97.5% to 100% for each task, with 95.3% of youth completing all tasks. Reliability was high, with reliability coefficients of >0.97 for 7 out of 8 QST parameters and minimal influence of examiner or participating site effects. Younger youth had lower pressure and heat pain thresholds (11-12 vs 13-18 years, d = -0.80 to -0.56) and cold pain tolerance (d = -0.33). Hispanic youth had higher pressure and heat pain thresholds (d = 0.37-0.45) and pain ratings for cold pain tolerance (d = 0.54) compared with non-Hispanic youth. No significant differences were observed in QST values by sex or personal contextual factors at the time of assessment (momentary pain, menstrual period, use of pain medications). Overall findings demonstrate feasibility of a brief QST protocol with youth with diverse acute MSK pain and data provide initial support for the reliability of this QST protocol for multisite research studies.

Perioperative Sleep Disturbance Following Mastectomy: A Longitudinal Investigation of the Relationship to Pain, Opioid Use, Treatment, and Psychosocial Symptoms.

OBJECTIVES: Sleep disturbance negatively impacts the quality of life and recovery. Our objective was to evaluate the relationship between the individual patient and surgical factors with greater sleep disturbance following breast surgery. METHODS: In this prospective longitudinal study, patients completed validated measures regarding sleep disturbance, pain, opioid use, and psychological symptoms preoperatively and then 2 weeks, 6 and 12 months postoperatively. Univariable and multivariable generalized estimating equations evaluated demographic, surgical, pain, and psychological predictors of sleep disturbance during the first year after breast surgery. RESULTS: Female patients (n=259) reported varying degrees of sleep disturbance, which were longitudinally associated with pain and psychosocial factors (eg, anxiety, depression, and affect). Independent preoperative predictors of worse sleep disturbance included younger age (B=-0.09, P =0.006), opioid use (B=3.09, P =0.02), and higher pain (B=0.19, P =<0.001) and anxiety (B=0.45, P =<0.001) at baseline. In addition, higher baseline positive affect (B=-0.14, P =<0.012) and the surgical category total mastectomy without reconstruction (B=-2.81, P =<0.006) were independently associated with lower sleep disturbance. Those with worse baseline sleep required more opioid analgesics during surgical recovery, and continued use of opioids at 2 weeks postsurgery was associated with disturbed sleep. DISCUSSION: Certain patient characteristics, including younger age and baseline anxiety, positive affect, pain, and opioid use, were associated with greater sleep disturbance in the first year after breast surgery. Sleep disturbance was also associated with the greater perioperative and postoperative opioid requirements. Preoperative interventions (eg, anxiety management, cultivating positive affect, and multimodal pain management) in high-risk individuals may enhance sleep and recovery postoperatively, and allow more moderate and less prolonged opioid use.

Back Pain Consortium (BACPAC): Protocol and Pilot Study Results for a Randomized Comparative-Effectiveness Trial of Antidepressants, Fear Avoidance Rehabilitation, or the Combination for Chronic Low Back Pain and Comorbid High Negative Affect.

OBJECTIVE: Patients with chronic low back pain (CLBP) and comorbid depression or anxiety disorders are highly prevalent. Negative affect (NA) refers to a combination of negative thoughts, emotions, and behaviors. Patients with CLBP with high NA have greater pain, worse treatment outcomes, and greater prescription opioid misuse. We present the protocol for SYNNAPTIC (SYNergizing Negative Affect & Pain Treatment In Chronic pain). DESIGN: A randomized comparative-effectiveness study of antidepressants, fear-avoidance rehabilitation, or their combination in 300 patients with CLBP with high NA. In the antidepressant- or rehabilitation-only arms, SYNNAPTIC includes an adaptive design of re-randomization after 4 months for nonresponders. SETTING: A multisite trial conducted in routine pain clinical treatment settings: pain clinics and physical and occupational therapy treatment centers. METHODS: Inclusion criteria include CLBP with elevated depression and anxiety symptoms. Antidepressant and rehabilitation treatments follow validated and effective protocols for musculoskeletal pain in patients with high NA. Power and sample size are based on superior outcomes of combination therapy with these same treatments in a 71-subject 4-arm pilot randomized controlled trial. CONCLUSIONS: SYNNAPTIC addresses the lack of evidence-based protocols for the treatment of the vulnerable subgroup of patients with CLBP and high NA. We hypothesize that combination therapy of antidepressants plus fear-avoidance rehabilitation will be more effective than each treatment alone. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04747314.

Brief Mindfulness-Based Cognitive Behavioral Therapy is Associated with Faster Recovery in Patients Undergoing Total Knee Arthroplasty: A Pilot Clinical Trial.

OBJECTIVE: To assess whether brief mindfulness-based cognitive behavioral therapy (MBCBT) could enhance the benefits of total knee arthroplasty (TKA) in improving pain and pain-related disability. Specifically, to determine 1) whether patients who received MBCBT differed from matched controls who received treatment-as-usual with regard to postsurgical pain outcomes and 2) whether changes in pain catastrophizing, depression, or anxiety explained the potential effects of MBCBT on pain outcomes. DESIGN: Pilot clinical trial. SETTING: An academic teaching hospital serving a large urban and suburban catchment area surrounding the Boston, Massachusetts metropolitan region. SUBJECTS: Sample of 44 patients undergoing TKA. Patients who completed a brief MBCBT intervention (n = 22) were compared with age-, race-, and sex-matched controls who received treatment-as-usual (n = 22). METHODS: The MBCBT intervention included four 60-minute sessions delivered by a pain psychologist in person and via telephone during the perioperative period. Participants were assessed at baseline and at 6 weeks, 3 months, and 6 months after surgery. RESULTS: Compared with matched controls, patients who received MBCBT had lower pain severity and pain interference at 6 weeks after surgery. Group differences in outcomes were mediated by changes in pain catastrophizing but not by changes in depression or anxiety. The MBCBT group had similar reductions in pain severity and interference as the control group did at 3 and 6 months after surgery. CONCLUSIONS: This work offers evidence for a safe and flexibly delivered nonpharmacological treatment (MBCBT) to promote faster recovery from TKA and identifies change in pain catastrophizing as a mechanism by which this intervention could lead to enhanced pain-related outcomes.

Increased Clinical Pain Locations and Pain Sensitivity in Women After Breast Cancer Surgery: Influence of Aromatase Inhibitor Therapy.

OBJECTIVES: Aromatase inhibitors (AIs), which potently inhibit estrogen biosynthesis, are a standard treatment for hormone sensitive early-stage breast cancer. AIs have been associated with substantial joint pain and muscle stiffness (aromatase inhibitor-associated musculoskeletal syndrome). However, the link between AIs and number of clinical pain locations and pain sensitivity are less well understood. The aim of this study was to compare longitudinal changes in clinical pain and quantitative pain sensitivity between women who did or did not receive AI therapy. METHODS: Women with early-stage breast cancer were prospectively enrolled and assessed for clinical pain in surgical and nonsurgical body areas using the Brief Pain Inventory and Breast Cancer Pain Questionnaire, and for pain sensitivity using quantitative sensory testing preoperatively and at 1 year postoperatively. Pain outcomes between participants who did and did not begin adjuvant AI therapy were compared using Wilcoxon Signed-Ranks and generalized estimating equation linear regression analyses. RESULTS: Clinical pain and pain sensitivity were comparable between AI (n=49) and no-AI (n=106) groups preoperatively. After adjusting for body mass index, AI therapy was associated with a greater increase in the number of painful nonsurgical body sites (significant time by treatment interaction, P =0.024). Pain location was most frequent in knees (28%), lower back (26%), and ankles/feet (17%). Quantitative sensory testing revealed a significant decrease in pain sensitivity (increased pressure pain threshold) in the no-AI group over time, but not in the AI group. CONCLUSIONS: AI therapy was associated with increased diffuse joint-related pain and greater post-treatment pain sensitivity, potentially implicating central sensitization as a contributing pain mechanism of aromatase inhibitor-associated musculoskeletal syndrome worthy of future investigation.

Early postoperative psychological distress as a mediator of subsequent persistent postsurgical pain outcomes among younger breast cancer patients.

PURPOSE: Younger age is a risk factor for worse pain outcomes following breast cancer surgery, yet little is known about how younger women's psychological state may contribute to their pain experience. Using prospectively collected longitudinal data from a surgical cohort, we examined whether early postoperative psychological distress at 2 weeks mediated the association between younger age and subsequent worse pain-related functioning 3 months after surgery. METHODS: Patients (N = 159) were recruited before breast cancer surgery into this longitudinal cohort study. Age at time of surgery, psychological distress (anxiety, depression, and sleep disturbance) assessed 2 weeks postoperatively, and impact of surgical pain on cognitive/emotional functioning and physical functioning assessed 3 months postoperatively were used for analysis. RESULTS: Younger age was associated with greater depression, anxiety, and sleep disturbance 2 weeks postoperatively. Younger age was also associated with greater ratings of pain impacting cognitive/emotional functioning and physical functioning 3 months postoperatively. The association between younger age and worse cognitive/emotional impact of pain was mediated by greater anxiety and sleep disturbance. Similarly, the association between younger age and worse physical impact of pain was mediated by greater sleep disturbance. CONCLUSION: The degree of anxiety and sleep disturbance that occur early after breast surgery may contribute to greater chronic pain-related functional disability among younger patients. Anxiety and sleep disturbance are modifiable with behavioral interventions, making them potential perioperative targets to improve long-term outcomes in young breast cancer survivors.

Increased pain catastrophizing longitudinally predicts worsened pain severity and interference in patients with chronic pain and cancer: A collaborative health outcomes information registry study (CHOIR).

OBJECTIVE: Little is known about how changes in psychosocial factors impact changes in pain outcomes among patients with cancer and chronic pain. This longitudinal cohort study of cancer patients investigated the relationships between changes in psychosocial factors and changes in pain severity and interference over time. METHODS: Data from patients with cancer and chronic pain (n = 316) treated at a tertiary pain clinic were prospectively collected. At their baseline visit (Time 1), patients provided demographic and clinical information, and completed validated psychosocial and pain assessments. Psychosocial and pain assessments were repeated at a follow-up visit (Time 2), on average 4.9 months later. Change scores (Time 2-Time 1) were computed for psychosocial and pain variables. Multivariable hierarchical linear regressions assessed the associations between changes in psychosocial factors with changes in pain outcomes over time. RESULTS: Participants were an average age of 59 years, were 61% female, and 69% White. Overall, a decrease in pain severity (p ≤ 0.001), but not pain interference, was observed among the group over time. In multivariable analyses, increased pain catastrophizing was significantly associated with increased pain severity over time (ß = 0.24, p ≤ 0.001). Similarly, increased pain catastrophizing (ß = 0.21, p ≤ 0.001) and increased depression (ß = 0.20, p ≤ 0.003) were significantly associated with increased pain interference over time. Demographic and clinical characteristics were not significantly related to changes in pain outcomes. CONCLUSIONS: Increased pain catastrophizing was uniquely associated with increased chronic pain severity and interference. Our findings indicate that cancer patients with chronic pain would likely benefit from the incorporation of nonpharmacological interventions, simultaneously addressing pain and psychological symptoms.