Statistical modeling of acute and chronic pain patient-reported outcomes obtained from ecological momentary assessment.

ABSTRACT: Ecological momentary assessment (EMA) allows for the collection of participant-reported outcomes (PROs), including pain, in the normal environment at high resolution and with reduced recall bias. Ecological momentary assessment is an important component in studies of pain, providing detailed information about the frequency, intensity, and degree of interference of individuals' pain. However, there is no universally agreed on standard for summarizing pain measures from repeated PRO assessment using EMA into a single, clinically meaningful measure of pain. Here, we quantify the accuracy of summaries (eg, mean and median) of pain outcomes obtained from EMA and the effect of thresholding these summaries to obtain binary clinical end points of chronic pain status (yes/no). Data applications and simulations indicate that binarizing empirical estimators (eg, sample mean, random intercept linear mixed model) can perform well. However, linear mixed-effect modeling estimators that account for the nonlinear relationship between average and variability of pain scores perform better for quantifying the true average pain and reduce estimation error by up to 50%, with larger improvements for individuals with more variable pain scores. We also show that binarizing pain scores (eg, <3 and ≥3) can lead to a substantial loss of statistical power (40%-50%). Thus, when examining pain outcomes using EMA, the use of linear mixed models using the entire scale (0-10) is superior to splitting the outcomes into 2 groups (<3 and ≥3) providing greater statistical power and sensitivity.

Methods for pragmatic randomized clinical trials of pain therapies: IMMPACT statement.

ABSTRACT: Pragmatic, randomized, controlled trials hold the potential to directly inform clinical decision making and health policy regarding the treatment of people experiencing pain. Pragmatic trials are designed to replicate or are embedded within routine clinical care and are increasingly valued to bridge the gap between trial research and clinical practice, especially in multidimensional conditions, such as pain and in nonpharmacological intervention research. To maximize the potential of pragmatic trials in pain research, the careful consideration of each methodological decision is required. Trials aligned with routine practice pose several challenges, such as determining and enrolling appropriate study participants, deciding on the appropriate level of flexibility in treatment delivery, integrating information on concomitant treatments and adherence, and choosing comparator conditions and outcome measures. Ensuring data quality in real-world clinical settings is another challenging goal. Furthermore, current trials in the field would benefit from analysis methods that allow for a differentiated understanding of effects across patient subgroups and improved reporting of methods and context, which is required to assess the generalizability of findings. At the same time, a range of novel methodological approaches provide opportunities for enhanced efficiency and relevance of pragmatic trials to stakeholders and clinical decision making. In this study, best-practice considerations for these and other concerns in pragmatic trials of pain treatments are offered and a number of promising solutions discussed. The basis of these recommendations was an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) meeting organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks.

Qualitative findings from a randomized trial of mindfulness-based and cognitive-behavioral group therapy for opioid-treated chronic low back pain.

This article reports qualitative outcomes from a randomized controlled trial comparing eight weeks of cognitive-behavioral group therapy for chronic pain (CBT-CP) and mindfulness-based group therapy (MBT) in individuals with chronic low back pain (CLBP). Approximately 10 months post-treatment, 108 participants completed structured qualitative interviews to express how the study treatment affected their life or health. Responses were qualitatively analyzed to generate a set of themes and subthemes, with between-groups comparisons to evaluate differences (if any) in treatment-response between MBT and CBT-CP. A majority of participants (n = 88, 81.5%) across both groups reflected positively on the study intervention and outcomes, identifying benefits in pain management (31.5%), meditation and mindfulness skills (25.9%), and relaxation skills (22.2%). Perceived benefits varied widely, suggesting no one intervention may be ideal for CLBP. Future research should examine tailoring interventions to target diverse clinical presentations to achieve optimal outcomes.

Pain Catastrophizing Moderates the Relationship Between Pain Sensitivity and Clinical Pain in Adolescents With Functional Abdominal Pain.

Pain catastrophizing has been linked to amplified pain sensitivity assessed using quantitative sensory testing (QST) in adults; pediatric data are limited, particularly in youth with functional abdominal pain (FAP). With increasing use of QST to evaluate somatosensory function and predict pain outcomes, we examined the associations between QST and clinical pain in adolescents with FAP and tested the moderating effects of pain catastrophizing. Seventy-seven adolescents (mean age 16.6 years, 85.7% female, 72.7% White, 90.8% non-Hispanic) who fulfilled diagnostic criteria for FAP completed QST assessment (pressure pain threshold and tolerance, heat pain threshold, conditioned pain modulation) and measures of abdominal pain intensity, pain interference, and pain catastrophizing. Adjusting for age and sex, only higher heat pain threshold was associated with higher abdominal pain intensity (Beta per 1-standard deviation = .54, P = .026). Contrary to hypothesis, for youth with higher pain catastrophizing, higher pressure pain tolerance was associated with greater abdominal pain intensity, but associations were not significant for youth with lower catastrophizing (P = .049). Similarly, for those with higher pain catastrophizing (in contrast to lower pain catastrophizing), higher pressure pain thresholds and tolerance were associated with higher pain interference (P = .039, .004, respectively). Results highlight the need to investigate the influence of pain catastrophizing on QST. PERSPECTIVE: This study demonstrated unexpected findings of pain catastrophizing moderating the relationships between pressure pain threshold and tolerance, and clinical pain in adolescents with FAP. This raised questions regarding our understanding of psychological contributions to QST findings in pediatric populations with chronic pain.

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.

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).

Patient engagement in designing, conducting, and disseminating clinical pain research: IMMPACT recommended considerations.

ABSTRACT: In the traditional clinical research model, patients are typically involved only as participants. However, there has been a shift in recent years highlighting the value and contributions that patients bring as members of the research team, across the clinical research lifecycle. It is becoming increasingly evident that to develop research that is both meaningful to people who have the targeted condition and is feasible, there are important benefits of involving patients in the planning, conduct, and dissemination of research from its earliest stages. In fact, research funders and regulatory agencies are now explicitly encouraging, and sometimes requiring, that patients are engaged as partners in research. Although this approach has become commonplace in some fields of clinical research, it remains the exception in clinical pain research. As such, the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials convened a meeting with patient partners and international representatives from academia, patient advocacy groups, government regulatory agencies, research funding organizations, academic journals, and the biopharmaceutical industry to develop consensus recommendations for advancing patient engagement in all stages of clinical pain research in an effective and purposeful manner. This article summarizes the results of this meeting and offers considerations for meaningful and authentic engagement of patient partners in clinical pain research, including recommendations for representation, timing, continuous engagement, measurement, reporting, and research dissemination.

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.

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.

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.

sEMG Biofeedback for Episodic Migraines: A Pilot Randomized Clinical Trial.

The aim of this study was to assess the feasibility and potential effectiveness of a 6-week virtual sEMG biofeedback intervention for patients with episodic migraines. Patients with episodic migraines were randomized to treatment with a novel surface EMG (sEMG) at-home biofeedback device or a treatment as usual control group; they completed validated baseline and post-intervention assessments of migraine related disability (migraine-specific quality of life, anxiety and depression). Participants also underwent a series of Quantitative Sensory Testing (QST) procedures referring to several different tests that quantitatively assess responses to mechanical stimuli during two separate visits (baseline and post intervention). No adverse events were reported during the study. Compared to the treatment as usual comparison group, patients in the sEMG biofeedback group reported lower migraine disability (p < 0.05). Compared to baseline, participants in the sEMG biofeedback group demonstrated statistically significant reductions in anxiety (p < 0.01), and significant increases in quality of life (p < 0.001), and significant decreases in temporal summation (p < 0.05) assessed by QST. No significant changes were observed in any of the outcomes in the control comparison group (p > 0.05). No significant changes were observed in migraine frequency in either of the two groups (p > 0.05). In addition, mediation analyses revealed that changes in migraine related quality of life mediated group effects on changes in migraine disability. Virtual sEMG biofeedback shows promise as a potential therapy for reducing disability, anxiety and depression and improving quality of life in individuals with episodic migraines. These results demonstrate the feasibility of a digital intervention for migraines and set the basis for conducting a future, larger scale randomized controlled trial to confirm these preliminary findings.

[ 11 C]-PBR28 positron emission tomography signal as an imaging marker of joint inflammation in knee osteoarthritis.

ABSTRACT: Although inflammation is known to play a role in knee osteoarthritis (KOA), inflammation-specific imaging is not routinely performed. In this article, we evaluate the role of joint inflammation, measured using [ 11 C]-PBR28, a radioligand for the inflammatory marker 18-kDa translocator protein (TSPO), in KOA. Twenty-one KOA patients and 11 healthy controls (HC) underwent positron emission tomography/magnetic resonance imaging (PET/MRI) knee imaging with the TSPO ligand [ 11 C]-PBR28. Standardized uptake values were extracted from regions-of-interest (ROIs) semiautomatically segmented from MRI data, and compared across groups (HC, KOA) and subgroups (unilateral/bilateral KOA symptoms), across knees (most vs least painful), and against clinical variables (eg, pain and Kellgren-Lawrence [KL] grades). Overall, KOA patients demonstrated elevated [ 11 C]-PBR28 binding across all knee ROIs, compared with HC (all P 's < 0.005). Specifically, PET signal was significantly elevated in both knees in patients with bilateral KOA symptoms (both P 's < 0.01), and in the symptomatic knee ( P < 0.05), but not the asymptomatic knee ( P = 0.95) of patients with unilateral KOA symptoms. Positron emission tomography signal was higher in the most vs least painful knee ( P < 0.001), and the difference in pain ratings across knees was proportional to the difference in PET signal ( r = 0.74, P < 0.001). Kellgren-Lawrence grades neither correlated with PET signal (left knee r = 0.32, P = 0.19; right knee r = 0.18, P = 0.45) nor pain ( r = 0.39, P = 0.07). The current results support further exploration of [ 11 C]-PBR28 PET signal as an imaging marker candidate for KOA and a link between joint inflammation and osteoarthritis-related pain severity.

Mindfulness-based Interventions for Chronic Low Back Pain: A Systematic Review and Meta-analysis.

OBJECTIVE: This systematic review aimed to compile existing evidence examining the effects of mindfulness-based interventions (MBIs) for chronic low back pain (CLBP). CLBP leads to millions of disabled individuals in the United States each year. Current pharmacologic treatments are only modestly effective and may present long-term safety issues. MBIs, which have an excellent safety profile, have been shown in prior studies to be effective in treating CLBP yet remained underutilized. DESIGN: Ovid/Medline, PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs), pilot RCTs, and single-arm studies that explored the effectiveness of MBIs in CLBP. METHODS: Separate searches were conducted to identify trials that evaluated MBIs in reducing pain intensity in individuals with CLBP. A meta-analysis was then performed using R v3.2.2, Metafor package v 1.9-7. RESULTS: Eighteen studies used validated patient-reported pain outcome measures and were therefore included in the meta-analysis. The MBIs included mindfulness meditation, mindfulness-based stress reduction, mindfulness-based cognitive therapy, mindfulness-oriented recovery enhancement, acceptance and commitment therapy, dialectical behavioral therapy, meditation-cognitive behavioral therapy, mindfulness-based care for chronic pain, self-compassion course, and loving-kindness course. Pain intensity scores were reported using a numerical rating scale (0 to 10) or an equivalent scale. The meta-analysis revealed that MBIs have a beneficial effect on pain intensity with a large-sized effect in adults with CLBP. CONCLUSIONS: MBIs seem to be beneficial in reducing pain intensity. Although these results were informative, findings should be carefully interpreted due to the limited data the high variability in study methodologies, small sample sizes, inclusion of studies with high risk of bias, and reliance on pre-post treatment differences with no attention to maintenance of effects. More large-scale RCTs are needed to provide reliable effect size estimates for MBIs in persons with CLBP.

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.

Thalamic neurometabolite alterations in chronic low back pain: a common phenomenon across musculoskeletal pain conditions?

ABSTRACT: Recently, we showed that patients with knee osteoarthritis (KOA) demonstrate alterations in the thalamic concentrations of several metabolites compared with healthy controls: higher myo-inositol (mIns), lower N-acetylaspartate (NAA), and lower choline (Cho). Here, we evaluated whether these metabolite alterations are specific to KOA or could also be observed in patients with a different musculoskeletal condition, such as chronic low back pain (cLBP). Thirty-six patients with cLBP and 20 healthy controls were scanned using 1 H-magnetic resonance spectroscopy (MRS) and a PRESS (Point RESolved Spectroscopy) sequence with voxel placement in the left thalamus. Compared with healthy controls, patients with cLBP demonstrated lower absolute concentrations of NAA ( P = 0.0005) and Cho ( P < 0.05) and higher absolute concentrations of mIns ( P = 0.01) when controlling for age, as predicted by our previous work in KOA. In contrast to our KOA study, mIns levels in this population did not significantly correlate with pain measures (eg, pain severity or duration). However, exploratory analyses revealed that NAA levels in patients were negatively correlated with the severity of sleep disturbance ( P < 0.01), which was higher in patients compared with healthy controls ( P < 0.001). Additionally, also in patients, both Cho and mIns levels were positively correlated with age ( P < 0.01 and P < 0.05, respectively). Altogether, these results suggest that thalamic metabolite changes may be common across etiologically different musculoskeletal chronic pain conditions, including cLBP and KOA, and may relate to symptoms often comorbid with chronic pain, such as sleep disturbance. The functional and clinical significance of these brain changes remains to be fully understood.

Change in Pain During Physical Activity Following Total Knee Arthroplasty: Associations With Improved Physical Function and Decreased Situational Pain Catastrophizing.

Background and Objectives: Knee osteoarthritis is one of the primary causes of chronic pain among older adults and because of the aging population, the number of total knee arthroplasties (TKAs) performed is exponentially increasing. While pain reduction is a goal of TKA, movement-evoked pain is rarely assessed pre- and post-TKA. We characterized the distributions of change in pain, function, and situational catastrophizing in patients from presurgery to 3 months postsurgery and explored associations among these pre-post changes. Research Design and Methods: This prospective study longitudinally assessed movement-evoked pain, function, and situational catastrophizing in patients with knee osteoarthritis (N = 92) using in-person performance-based tests (6-min walk test [6MWT], stair-climb test [SCT]) prior to and 3 months after TKA. Patients also completed the Western Ontario McMaster Universities Scales (WOMAC) pain and function subscales, and Pain Catastrophizing Scale, presurgery and 3- and 6-months postsurgery. Results: Movement-evoked pain and function on performance tests significantly improved from pre- to post-TKA. Improved SCT function was associated with reduced SCT pain and catastrophizing. Similarly, reduced pain during the SCT was associated with reduced catastrophizing during the SCT. However, 6MWT function was not associated with 6MWT pain or catastrophizing; yet reduced pain during the 6MWT was associated with reduced catastrophizing during the 6MWT. Reduced movement-evoked pain during both performance tests was consistently associated with improved WOMAC function and pain, whereas improved function on performance tests was inconsistently associated with WOMAC function and pain. Notably, greater movement-evoked pain on both performance tests at 3-month post-TKA was associated with worse WOMAC function and pain at 6 months, whereas better function on performance tests at 3 months was associated with better WOMAC function, but not related to WOMAC pain at 6 months. Discussion and Implications: Findings highlight the importance of situation-specific and in vivo assessments of pain and catastrophizing during physical activity.