Brain-to-brain mechanisms underlying pain empathy and social modulation of pain in the patient-clinician interaction.

Social interactions such as the patient-clinician encounter can influence pain, but the underlying dynamic interbrain processes are unclear. Here, we investigated the dynamic brain processes supporting social modulation of pain by assessing simultaneous brain activity (fMRI hyperscanning) from chronic pain patients and clinicians during video-based live interaction. Patients received painful and nonpainful pressure stimuli either with a supportive clinician present (Dyadic) or in isolation (Solo). In half of the dyads, clinicians performed a clinical consultation and intake with the patient prior to hyperscanning (Clinical Interaction), which increased self-reported therapeutic alliance. For the other half, patient-clinician hyperscanning was completed without prior clinical interaction (No Interaction). Patients reported lower pain intensity in the Dyadic, relative to the Solo, condition. In Clinical Interaction dyads relative to No Interaction, patients evaluated their clinicians as better able to understand their pain, and clinicians were more accurate when estimating patients' pain levels. In Clinical Interaction dyads, compared to No Interaction, patients showed stronger activation of the dorsolateral and ventrolateral prefrontal cortex (dlPFC and vlPFC) and primary (S1) and secondary (S2) somatosensory areas (Dyadic-Solo contrast), and clinicians showed increased dynamic dlPFC concordance with patients' S2 activity during pain. Furthermore, the strength of S2-dlPFC concordance was positively correlated with self-reported therapeutic alliance. These findings support that empathy and supportive care can reduce pain intensity and shed light on the brain processes underpinning social modulation of pain in patient-clinician interactions. Our findings further suggest that clinicians' dlPFC concordance with patients' somatosensory processing during pain can be boosted by increasing therapeutic alliance.

The association between changes in clinical pain severity and IL-6 reactivity among patients undergoing total knee Arthroplasty: The moderating role of change in insomnia.

Knee osteoarthritis (KOA) is linked to an enhanced release of interleukin-6 (IL-6). Increased levels of IL-6 are associated with greater pain and insomnia. While total knee arthroplasty (TKA) typically results in the reduction of pain, for a subgroup of patients, pain does not improve. Understanding patients' propensity to upregulate IL-6 may provide insight into variation in the clinical success of TKA for improving pain, and insomnia may play an important modulatory role. We investigated the association between pre- and post-surgical changes in clinical pain and IL-6 reactivity, and whether change in insomnia moderated this association. Patients (n = 39) with KOA came in-person before and 3-months after TKA. At both visits, patients completed validated measures of clinical pain and insomnia, as well as underwent quantitative sensory testing (QST). Blood samples were collected to analyze IL-expression both before and after QST procedures to assess changes in IL-6 in response to QST (IL-6 reactivity). Patients were categorized into two groups based on change in clinical pain from pre- to post-surgery: 1) pain decreased > 2 points (pain improved) and 2) pain did not decrease > 2 points (pain did not improve). Based on this definition, 49 % of patients had improved pain at 3-months. Among patients with improved pain, IL-6 reactivity significantly decreased from pre- to post-surgery, whereas there was no significant change in IL-6 reactivity among those whose pain did not improve. There was also a significant interaction between pain status and change in insomnia, such that among patients whose insomnia decreased over time, improved pain was significantly associated with a reduction in IL-6 reactivity. However, among patients whose insomnia increased over time, pain status and change in IL-6 reactivity were not significantly associated. Our findings suggest that the resolution of clinical pain after TKA may be associated with discernible alterations in pro-inflammatory responses that can be measured under controlled laboratory conditions, and this association may be moderated by perioperative changes in insomnia. Randomized controlled trials which carefully characterize the phenotypic features of patients are needed to understand how and for whom behavioral interventions may be beneficial in modulating inflammation, pain, and insomnia.

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.

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).

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.

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.

Neuroimmune signatures in chronic low back pain subtypes.

We recently showed that patients with different chronic pain conditions (such as chronic low back pain, fibromyalgia, migraine and Gulf War illness) demonstrated elevated brain and/or spinal cord levels of the glial marker 18-kDa translocator protein (TSPO), which suggests that neuroinflammation might be a pervasive phenomenon observable across multiple aetiologically heterogeneous pain disorders. Interestingly, the spatial distribution of this neuroinflammatory signal appears to exhibit a degree of disease specificity (e.g. with respect to the involvement of the primary somatosensory cortex), suggesting that different pain conditions may exhibit distinct 'neuroinflammatory signatures'. To explore this hypothesis further, we tested whether neuroinflammatory signal can characterize putative aetiological subtypes of chronic low back pain patients based on clinical presentation. Specifically, we explored neuroinflammation in patients whose chronic low back pain either did or did not radiate to the leg (i.e. 'radicular' versus 'axial' back pain). Fifty-four patients with chronic low back pain, 26 with axial back pain [43.7 ± 16.6 years old (mean ± SD)] and 28 with radicular back pain (48.3 ± 13.2 years old), underwent PET/MRI with 11C-PBR28, a second-generation radioligand for TSPO. 11C-PBR28 signal was quantified using standardized uptake values ratio (validated against volume of distribution ratio; n = 23). Functional MRI data were collected simultaneously to the 11C-PBR28 data (i) to functionally localize the primary somatosensory cortex back and leg subregions; and (ii) to perform functional connectivity analyses (in order to investigate possible neurophysiological correlations of the neuroinflammatory signal). PET and functional MRI measures were compared across groups, cross-correlated with one another and with the severity of 'fibromyalgianess' (i.e. the degree of pain centralization, or 'nociplastic pain'). Furthermore, statistical mediation models were used to explore possible causal relationships between these three variables. For the primary somatosensory cortex representation of back/leg, 11C-PBR28 PET signal and functional connectivity to the thalamus were: (i) higher in radicular compared to axial back pain patients; (ii) positively correlated with each other; (iii) positively correlated with fibromyalgianess scores, across groups; and finally (iv) fibromyalgianess mediated the association between 11C-PBR28 PET signal and primary somatosensory cortex-thalamus connectivity across groups. Our findings support the existence of 'neuroinflammatory signatures' that are accompanied by neurophysiological changes and correlate with clinical presentation (in particular, with the degree of nociplastic pain) in chronic pain patients. These signatures may contribute to the subtyping of distinct pain syndromes and also provide information about interindividual variability in neuroimmune brain signals, within diagnostic groups, that could eventually serve as targets for mechanism-based precision medicine approaches.

The mediating effect of social functioning on the relationship between catastrophizing and pain among patients with chronic low back pain.

OBJECTIVE: Pain catastrophizing can be characterized as an interpersonal form of coping used to elicit support or empathy from others. Despite intentions of increasing support, catastrophizing can impair social functioning. While considerable work has addressed the relationship between catastrophizing and pain, limited empirical work has examined this relationship within a social context. First, we examined the role of catastrophizing as a potential contributor to group differences (chronic low back pain [cLBP] vs pain-free controls) in social functioning. Then we conducted a follow-up, exploratory analysis to examine the relationships between catastrophizing, social functioning, and pain within the subgroup of participants with cLBP. METHODS: In this observational study, participants with cLBP (N = 62) and pain-free controls (N = 79) completed validated measures of pain, social functioning, and pain catastrophizing. A mediation analysis was conducted to examine whether catastrophizing mediated group differences (cLBP vs controls) in social functioning. A follow-up, exploratory mediation analysis then tested whether social functioning mediated the association between catastrophizing and pain within the subgroup of cLBP participants. RESULTS: Participants with cLBP reported higher levels of pain, impaired social functioning, and higher catastrophizing compared to pain-free controls. Catastrophizing partially mediated the group difference in impaired social functioning. Additionally, social functioning mediated the association between higher catastrophizing and greater pain within the subgroup of cLBP participants. CONCLUSIONS: We showed that impaired social functioning was driving the relationship between higher pain catastrophizing and worse pain among participants with cLBP. Interventions, such as cognitive behavioral therapy, should address catastrophizing in individuals with cLBP, while simultaneously improving social functioning.

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.

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.

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.

Adapting Brief Behavioral Treatment for Insomnia for Former National Football League Players: A Pilot Study.

OBJECTIVES: Insomnia is highly prevalent among persons with chronic pain. Although cognitive behavioral therapy for insomnia is recommended as first-line treatment for insomnia, it is underutilized. We tested the feasibility of a potentially scalable alternative - Brief Behavioral Therapy for Insomnia (BBTI) for former National Football League (NFL) players, a group with a high prevalence of chronic pain. We assessed changes in sleep, pain, and psychological health. METHODS: Single-arm clinical trial of an adapted telephone-delivered BBTI intervention in 40 former NFL players with insomnia. We collected data on changes in sleep, pain, and psychological health outcomes. RESULTS: Among former players (30% racial/ethnic minorities), BBTI was both acceptable and feasible. BBTI was associated with improvements in sleep disturbance (primary exploratory sleep outcome, mean T-score change -6.2, 95% CI: -7.6, -4.8), sleep-related impairment (mean T-score change -5.7, 95% CI: -7.9, -3.5) and insomnia severity (mean change -5.3, 95% CI: -6.8, -3.5) post-intervention. Improvements were maintained at 2-months. BBTI was also associated with improvements in pain interference and intensity, but not psychological health. CONCLUSION: An adapted telephone-delivered BBTI is acceptable and feasible among retired players with a range of insomnia symptoms and shows promise for improving sleep and pain. These data support the need for future trials assessing BBTI's effect on both sleep and pain outcomes.

Introversion, Extraversion, and Worsening of Chronic Pain Impact during Social Isolation: A Mediation Analysis.

COVID-19 social distancing mandates increased social isolation, resulting in changes in pain severity and interference among individuals with chronic pain. Differences in personality (e.g., introversion/extraversion) may modulate responses to social isolation. We examined the influence of introversion on reported social distancing-related increases in pain interference and assessed for mediators of this relationship. Individuals with chronic pain (n = 150) completed validated questionnaires 4-8 weeks after implementation of social distancing mandates. Introversion/extraversion was measured using a subscale of the Myers-Briggs Type Indicator and changes in pain and psychosocial variables were calculated by comparing participants' recalled and current scores. Association between introversion/extraversion and other variables were assessed using linear regression. A parallel mediation was used to examine mediators of the association between introversion and change in pain interference. Higher introversion was associated with a decrease in pain interference after social distancing (Rho = - .194, p = .017). Parallel mediation analysis revealed that the relationship between introversion/extraversion and change in pain interference was mediated by changes in sleep disturbance and depression, such that higher introversion was associated with less isolation-induced sleep disruption and depression, and thereby less worsening of pain interference. These findings suggest that personality factors such as introversion/extraversion should be considered when personalizing treatment of chronic pain.

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.

Profiles of Risk and Resilience in Chronic Pain: Loneliness, Social Support, Mindfulness, and Optimism Coming out of the First Pandemic Year.

OBJECTIVE: Individuals experience chronic pain differently, not only because of different clinical diagnoses, but also because of differing degrees of influence from biopsychosocial pain modulators. We aimed to cluster patients with chronic pain into distinct subgroups based on psychosocial characteristics and pain intensity, and we subsequently examined group differences in pain-related interference approximately 1 year later. METHODS: In this observational, longitudinal study, patients with chronic pain (n = 94) completed validated assessments of psychosocial characteristics and pain intensity at the beginning of COVID-19-related social distancing (April to June 2020). One year later (May to June 2021), patients completed a follow-up survey with assessments of pain interference, loneliness, social support, mindfulness, and optimism. RESULTS: A cluster analysis, using psychosocial factors and pain intensity, empirically produced three patient groups: 1) psychosocial predominant (PSP), characterized by high psychosocial distress and average pain intensity; 2) pain intensity predominant (PIP), characterized by average psychosocial distress and high pain intensity; and 3) less elevated symptoms (LES), characterized by low psychosocial distress and low pain intensity. At the 1-year follow-up, patients in the PSP and PIP clusters suffered greater pain interference than patients in the LES cluster, while patients in the PSP cluster also reported greater loneliness and lower mindfulness and optimism. CONCLUSIONS: An empirical psychosocial-based clustering of patients identified three distinct groups that differed in pain interference. Patients with high psychosocial modulation of pain at the onset of social distancing (the PSP cluster) suffered not only greater pain interference but also greater loneliness and lower levels of mindfulness and optimism, which suggests some potential behavioral targets for this group in the future.

The Influence of Expectancies on Pain and Function Over Time After Total Knee Arthroplasty.

OBJECTIVE: Expectancies have a well-documented influence on the experience of pain, responses to treatment, and postsurgical outcomes. In individuals with osteoarthritis, several studies have shown that expectations predict increased pain and disability after total knee replacement surgery. Despite the growing recognition of the importance of expectancies in clinical settings, few studies have examined the influence of expectancies throughout postsurgical recovery trajectories. The objective of the present study was to examine the role of presurgical expectancies on pain and function at 6-week, 6-month, and 1-year follow-ups after total knee arthroplasty. DESIGN AND PARTICIPANTS: Data were collected from patients scheduled for total knee arthroplasty 1 week before surgery and then at 6 weeks, 6 months, and 1 year after surgery. Correlational and multivariable regression analyses examined the influence of expectancies on patients' perceptions of pain reduction and functional improvement at each time point. Analyses controlled for age, sex, body mass index, presurgical pain intensity and function, pain catastrophizing, anxiety, and depression. RESULTS: Results revealed that expectancies significantly predicted pain reduction and functional improvement at 1-year follow-up. However, expectancies did not predict outcomes at the 6-week and 6-month follow-ups. Catastrophizing and depressive symptoms emerged as short-term predictors of postsurgical functional limitations at 6-week and 6-month follow-ups, respectively. CONCLUSIONS: The results suggest that targeting high levels of catastrophizing and depressive symptoms could optimize short-term recovery after total knee arthroplasty. However, the results demonstrate that targeting presurgical negative expectancies could prevent prolonged recovery trajectories, characterized by pain and loss of function up to 1 year after total knee arthroplasty.

The Effects of Combined Respiratory-Gated Auricular Vagal Afferent Nerve Stimulation and Mindfulness Meditation for Chronic Low Back Pain: A Pilot Study.

OBJECTIVE: Respiratory-gated Auricular Vagal Afferent Nerve stimulation (RAVANS) is a safe nonpharmacological approach to managing chronic pain. The purpose of the current study was to examine (1) the feasibility and acceptability of RAVANS, combined with mindful meditation (MM) for chronic low back pain (CLBP), (2) the potential synergy of MM+RAVANS on improving pain, and (3) possible moderators of the influence of MM+RAVANS on pain. DESIGN: Pilot feasibility and acceptability study. SETTING: Pain management center at large academic medical center. SUBJECTS: Nineteen adults with CLBP and previous MM training. METHODS: Participants attended two sessions during which they completed quantitative sensory testing (QST), rated pain severity, and completed a MM+stimulation session. Participants received RAVANS during one visit and sham stimulation during the other, randomized in order. Following intervention, participants repeated QST. RESULTS: MM+RAVANS was well tolerated, acceptable, and feasible to provide relief for CLBP. Both MM+stimulation sessions resulted in improved back pain severity, punctate pain ratings, and pressure pain threshold. Individuals with greater negative affect showed greater back pain improvement from MM+RAVANS while those with greater mindfulness showed greater back pain improvement from MM+sham. CONCLUSIONS: Results suggest that for CLBP patients with prior MM training, the analgesic effects of MM may have overshadowed effects of RAVANS given the brief single session MM+RAVANS intervention. However, those with greater negative affect may benefit from combined MM+RAVANS.