A preliminary examination of the effects of childhood abuse and resilience on pain and physical functioning in patients with knee osteoarthritis.

OBJECTIVES: We examined associations of a self-reported history of childhood abuse with pain and physical functioning in patients with knee osteoarthritis (KOA) awaiting total knee arthroplasty (TKA). We also explored the potential moderating effects of positive childhood experiences (PCEs), an index of resilience, on these associations. METHODS: Prior to TKA, participants with KOA awaiting surgery (N = 239) completed self-report measures of adverse childhood experiences (ACEs), PCEs, pain, and physical functioning. We evaluated associations of pain and physical functioning (Brief Pain Inventory [BPI] and Western Ontario and McMaster University of Osteoarthritis Index [WOMAC]) based on the experience of ACEs (childhood abuse), with PCEs (childhood happiness and supportive parental care) as potential moderators. RESULTS: Greater exposure to childhood abuse was positively correlated with BPI pain interference as well as WOMAC pain and functioning scores. Additionally, childhood happiness and supportive parental care moderated the positive associations of childhood abuse with pain and physical functioning; though, surprisingly, the adverse effects of childhood abuse on these outcomes were more pronounced among participants with high levels of childhood happiness and supportive parental care. CONCLUSION: Overall, results show an association between a self-reported history of childhood abuse and pain and functioning in patients with KOA awaiting TKA. However, PCEs did not protect against the negative consequences of childhood abuse in our cohort. Further research is needed to validate these associations and gain a more comprehensive understanding of the complex interplay between childhood abuse and PCEs and their potential influences on pain experiences in adults with chronic pain conditions, including KOA.

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.

Elevated pain sensitivity is associated with reduced rapid eye movement (REM) sleep in females with comorbid temporomandibular disorder and insomnia.

OBJECTIVE: Patients with chronic pain disorders, including Temporomandibular Disorders (TMDs) endorse high levels of sleep disturbances, frequently reporting reduced sleep quality. Despite this, little is known about the effect that daytime pain has on the microstructure and macro-architecture of sleep. Therefore, we aimed to examine the extent to which daytime pain sensitivity, measured using quantitative sensory testing (QST), is associated with objective sleep parameters the following night, including sleep architecture and power spectral density, in women with TMD. METHODS: 144 females with myalgia and arthralgia by examination using the Diagnostic criteria for TMD completed a comprehensive QST battery consisting of General Pain Sensitivity, Central Sensitization Index, and Masseter Pressure Pain Threshold assessments. Polysomnography was collected the same night to measure sleep architecture and calculate relative power in delta, theta, alpha, sigma, and beta power bands. RESULTS: Central Sensitization (B = -3.069, P = .009), General Pain Sensitivity Indices (B = -3.069, P = .007), and Masseter Pain Pressure Threshold (B = 0.030, P = .008) were significantly associated with lower REM% both before and after controlling for covariates. Pain sensitivity measures were not significantly associated with relative power in any of the spectral bands nor with any other sleep architectural stages. CONCLUSIONS: Our findings demonstrate that higher generalized pain sensitivity, masseter pain pressure threshold, as well as central sensitization were associated with a lower percentage of REM in participants with myofascial pain and arthralgia of the masticatory system. These findings provide an important step toward understanding the mechanistic underpinnings of how chronic pain interacts with sleep physiology.

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.

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.

Depressive and Insomnia Symptoms Sequentially Mediate the Association Between Racism-Based Discrimination in Healthcare Settings and Clinical Pain Among Adults With Sickle Cell Disease.

Racism-based discrimination in healthcare settings has been associated with clinical pain in adults living with sickle cell disease; however, no studies have examined depressive and insomnia symptoms as mechanisms that may drive this relationship. This secondary data analysis examined associations between depressive and insomnia symptoms, racism-based discrimination, and clinical pain. Seventy-one adults with sickle cell disease (70% female, Mage = 38.79) provided baseline reports of racism-based discrimination, depressive symptoms, insomnia symptoms, and pain (severity, interference, catastrophizing), and they completed daily diaries of pain severity and interference over 3 months. In a sequential mediation model, baseline depressive (1st) and insomnia symptoms (2nd) significantly mediated the association between racism-based discrimination and baseline pain interference, average daily diary pain severity, and average daily diary pain interference. Although the mediation model with baseline pain severity as the outcome was significant, the total and direct effects were not. Results indicate that discrimination in healthcare settings contributes to depression, which may act on pain through sleep disturbance. Findings support the need for systemic and structural changes to eliminate discrimination in healthcare settings and behavioral mood and sleep interventions to reduce the impact of discrimination on clinical pain. PERSPECTIVE: The relationship between discrimination in healthcare settings and pain in adults with sickle cell disease may be driven by depression and sleep disturbance, modifiable risk factors and potential treatment targets. Results suggest that systemic, structural, and institutional changes must be implemented to promote better patient care and health outcomes.

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.

Meditation Practice, Mindfulness, and Pain-Related Outcomes in Mindfulness-Based Treatment for Episodic Migraine.

Objectives: Mindfulness-based interventions (MBIs) have emerged as promising prophylactic episodic migraine treatments. The present study investigated biopsychosocial predictors and outcomes associated with formal, daily-life meditation practice in migraine patients undergoing MBI, and whether augmented mindfulness mechanistically underlies change. Methods: Secondary analyses of clinical trial data comparing a 12-week enhanced mindfulness-based stress reduction course (MBSR + ; n = 50) to stress management for headache (SMH; n = 48) were conducted. Results: Pre-treatment mesocorticolimbic system functioning (i.e., greater resting state ventromedial prefrontal cortex-right nucleus accumbens [vmPFC-rNAC] functional connectivity) predicted greater meditation practice duration over MBSR + (r = 0.58, p = 0.001), as well as the change in headache frequency from pre- to post-treatment (B = -12.60, p = 0.02) such that MBSR + participants with greater vmPFC-rNAC connectivity showed greater reductions in headache frequency. MBSR + participants who meditated more showed greater increases in mindfulness (B = 0.52, p = 0.02) and reductions in the helplessness facet of pain catastrophizing (B = -0.13, p = 0.01), but not headache frequency, severity, or impact. Augmented mindfulness mediated reductions in headache impact resulting from MBSR + , but not headache frequency. Conclusions: Mesocorticolimbic system function is implicated in motivated behavior, and thus, motivation-enhancing interventions might be delivered alongside mindfulness-based training to enhance meditation practice engagement. Formal, daily-life meditation practice duration appears to benefit pain-related cognitions, but not clinical pain, while mindfulness emerges as a mechanism of MBIs on headache impact, but not frequency. Further research is needed to investigate the day-to-day effects of formal, daily-life meditation practice on pain, and continue to characterize the specific mechanisms of MBIs on headache outcomes. Preregistration: This study is not preregistered.

Intensive Mindfulness Meditation Reduces Frequency and Burden of Migraine: An Unblinded Single-Arm Trial.

Objectives: Preventing migraine headaches and improving the quality of life for patients with migraine remains a challenge. We hypothesized intensive meditation training would reduce the disease burden of migraine. Method: An unblinded trial was analyzed as a single cohort exposed to a silent 10-day Vipassana meditation retreat that included 100 hr of sitting meditation. Participants with chronic or episodic migraine were enrolled and followed for 1 year. The primary outcome was a change in mean monthly migraine days at 12 months from baseline. Secondary outcomes included headache frequency and intensity, acute medication use, work days missed, home meditation, sleep quality, general health, quality of life, migraine impact, positive and negative affect, perceived stress, mindfulness, and pain catastrophizing. Results: Three hundred people were screened and 58 (19%) agreed to participate and enrolled in the intensive meditation training. Forty-six participants with chronic migraine (≥ 15 headaches/month of which ≥ 8 were migraines) and 12 with episodic migraine (< 15 and ≥ 4 migraines/month) attended and 45 (78%) completed the retreat. At 12 months, the average migraine frequency was reduced by 2.7 days (from 16.6 at baseline) per 28 days (95%CI - 4.3, - 1.3) and headaches by 3.4 (20.1 at baseline) per 28 days (- 4.9, - 1.9). Fifty percent responder rate was 29% for migraine. Acute medication use dropped by an average of 2.2 days (- 3.9, - 0.5) per 28 days, and participants reported 2.3 fewer days (- 4.0, - 0.5) on which they reduced their activity due to migraines. The most striking and promising effects were in several secondary outcomes, including migraine-specific quality of life, pain catastrophizing, and perceived stress. The significant improvements observed immediately following the intervention were sustained at 12 months follow-up. Conclusions: Training in Vipassana meditation via a 10-day retreat may reduce the frequency and burden of migraine. Preregistration: ClinicalTrials.gov: NCT00663585.

Is Mindfulness Associated With Lower Pain Reactivity and Connectivity of the Default Mode Network? A Replication and Extension Study in Healthy and Episodic Migraine Participants.

Formal training in mindfulness-based practices promotes reduced experimental and clinical pain, which may be driven by reduced emotional pain reactivity and undergirded by alterations in the default mode network, implicated in mind-wandering and self-referential processing. Recent results published in this journal suggest that mindfulness, defined here as the day-to-day tendency to maintain a non-reactive mental state in the absence of training, associates with lower pain reactivity, greater heat-pain thresholds, and resting-state default mode network functional connectivity in healthy adults in a similar manner to trained mindfulness. The extent to which these findings extend to chronic pain samples and replicate in healthy samples is unknown. Using data from healthy adults (n = 36) and episodic migraine patients (n = 98) and replicating previously published methods, we observed no significant association between mindfulness and heat-pain threshold, pain intensity or unpleasantness, or pain catastrophizing in healthy controls, or between mindfulness and headache frequency, severity, impactor pain catastrophizing in patients. There was no association between default mode network connectivity and mindfulness in either sample when probed via seed-based functional connectivity analyses. In post-hoc whole brain exploratory analyses, a meta-analytically derived default mode network node (ie, posterior cingulate cortex) showed connectivity with regions unassociated with pain processing as a function of mindfulness, such that healthy adults higher in mindfulness showed greater functional connectivity between the posterior cingulate cortex-and cerebellum. Collectively, these findings suggest that the relationship between mindfulness and default mode network functional connectivity may be nuanced or non-robust, and encourage further investigation of how mindfulness relates to pain. PERSPECTIVE: This study found few significant associations between dispositional mindfulness and pain, pain reactivity and default mode connectivity in healthy adults and migraine patients. The relationship between mindfulness and default mode network connectivity may be nuanced or non-robust.

Three Dimensions of Association Link Migraine Symptoms and Functional Connectivity.

Migraine is a heterogeneous disorder with variable symptoms and responsiveness to therapy. Because of previous analytic shortcomings, variance in migraine symptoms has been inconsistently related to brain function. In the current analysis, we used data from two sites (n = 143, male and female humans), and performed canonical correlation analysis, relating resting-state functional connectivity (RSFC) with a broad range of migraine symptoms, ranging from headache characteristics to sleep abnormalities. This identified three dimensions of covariance between symptoms and RSFC. The first dimension related to headache intensity, headache frequency, pain catastrophizing, affect, sleep disturbances, and somatic abnormalities, and was associated with frontoparietal and dorsal attention network connectivity, both of which are major cognitive networks. Additionally, RSFC scores from this dimension, both the baseline value and the change from baseline to postintervention, were associated with responsiveness to mind-body therapy. The second dimension was related to an inverse association between pain and anxiety, and to default mode network connectivity. The final dimension was related to pain catastrophizing, and salience, sensorimotor, and default mode network connectivity. In addition to performing canonical correlation analysis, we evaluated the current clustering of migraine patients into episodic and chronic subtypes, and found no evidence to support this clustering. However, when using RSFC scores from the three significant dimensions, we identified a novel clustering of migraine patients into four biotypes with unique functional connectivity patterns. These findings provide new insight into individual variability in migraine, and could serve as the foundation for novel therapies that take advantage of migraine heterogeneity.SIGNIFICANCE STATEMENT Using a large multisite dataset of migraine patients, we identified three dimensions of multivariate association between symptoms and functional connectivity. This analysis revealed neural networks that relate to all measured symptoms, but also to specific symptom ensembles, such as patient propensity to catastrophize painful events. Using these three dimensions, we found four biotypes of migraine informed by clinical and neural variation together. Such findings pave the way for precision medicine therapy for migraine.

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.

Association of affective state with the assimilation of daily pain expectancy and pain experience.

ABSTRACT: Expectancies for pain and pain relief are central to experimental models of placebo analgesia and nocebo hyperalgesia and are a promising target for clinical intervention in patients with chronic pain. Affective states may play an important role in modulating the degree to which expectancies influence pain, broadening the opportunities for intervention targets. However, findings to date have been mixed and mostly limited to laboratory designs. Few studies have examined the interplay of naturally occurring affective states, pain expectancies, and pain experiences in the course of daily life with chronic pain. In this study, patients with temporomandibular disorder reported their daily pain expectancies and affective states each morning and their daily pain experience each evening, over a 2-week period. Multilevel modeling analyses revealed the association of morning pain expectancies with subsequent pain experiences was moderated by morning positive affective state ( B = 0.04, SE = 0.02, t = 2.00, P = 0.046) such that the congruent assimilation of a low pain expectancy with a low pain experience was starkest when morning positive affect was higher than usual. Relatedly, higher morning positive affect predicted greater odds of experiencing a match between pain expectancies and pain experience when the expectation was for low, but not high, pain levels (odds ratio = 1.19, confidence interval: 1.01-1.41, P = 0.03). Negative affect, in contrast, did not significantly influence the assimilation of high pain expectancies with high pain experiences. These findings extend previous experimental studies by showing that the association of daily pain expectancies with pain experience varies as a function of affective state.

Multimodal prediction of pain and functional outcomes 6 months following total knee replacement: a prospective cohort study.

BACKGROUND: Knee osteoarthritis (OA) is among the most common and disabling persistent pain conditions, with increasing prevalence and impact around the globe. In the U.S., the rising prevalence of knee OA has been paralleled by an increase in annual rates of total knee arthroplasty (TKA), a surgical treatment option for late-stage knee OA. While TKA outcomes are generally good, post-operative trajectories of pain and functional status vary substantially; a significant minority of patients report ongoing pain and impaired function following TKA. A number of studies have identified sets of biopsychosocial risk factors for poor post-TKA outcomes (e.g., comorbidities, negative affect, sensory sensitivity), but few prospective studies have systematically evaluated the unique and combined influence of a broad array of factors. METHODS: This multi-site longitudinal cohort study investigated predictors of 6-month pain and functional outcomes following TKA. A wide spectrum of relevant biopsychosocial predictors was assessed preoperatively by medical history, patient-reported questionnaire, functional testing, and quantitative sensory testing in 248 patients undergoing TKA, and subsequently examined for their predictive capacity. RESULTS: The majority of patients had mild or no pain at 6 months, and minimal pain-related impairment, but approximately 30% reported pain intensity ratings of 3/10 or higher. Reporting greater pain severity and dysfunction at 6 months post-TKA was predicted by higher preoperative levels of negative affect, prior pain history, opioid use, and disrupted sleep. Interestingly, lower levels of resilience-related "positive" psychosocial characteristics (i.e., lower agreeableness, lower social support) were among the strongest, most consistent predictors of poor outcomes in multivariable linear regression models. Maladaptive profiles of pain modulation (e.g., elevated temporal summation of pain), while not robust unique predictors, interacted with psychosocial risk factors such that the TKA patients with the most pain and dysfunction exhibited lower resilience and enhanced temporal summation of pain. CONCLUSIONS: This study underscores the importance of considering psychosocial (particularly positively-oriented resilience variables) and sensory profiles, as well as their interaction, in understanding post-surgical pain trajectories.

Migraine disability, pain catastrophizing, and headache severity are associated with evoked pain and targeted by mind-body therapy.

ABSTRACT: Meta-analysis suggests that migraine patients are no more sensitive to experimentally evoked pain than healthy control subjects. At the same time, studies have linked some migraine symptoms to quantitative sensory testing (QST) profiles. Unfortunately, previous studies associating migraine symptoms and QST have important methodological shortcomings, stemming from small sample sizes, and frequent use of univariate statistics for multivariate research questions. In the current study, we seek to address these limitations by using a large sample of episodic migraine patients (n = 103) and a multivariate analysis that associates pain ratings from many thermal intensities simultaneously with 12 clinical measures ranging from headache frequency to sleep abnormalities. We identified a single dimension of association between thermal QST and migraine symptoms that relates to pain ratings for all stimulus intensities and a subset of migraine symptoms relating to disability (Headache Impact Test 6 and Brief Pain Inventory interference), catastrophizing (Pain Catastrophizing Scale), and pain severity (average headache pain, Brief Pain Inventory severity, and Short-Form McGill Pain Questionnaire 2). Headache frequency, allodynia, affect, and sleep disturbances were unrelated to this dimension. Consistent with previous research, we did not observe any difference in QST ratings between migraine patients and healthy control subjects. Additionally, we found that the linear combination of symptoms related to QST was modified by the mind-body therapy enhanced mindfulness-based stress reduction (MBSR+). These results suggest that QST has a selective relationship with pain symptoms even in the absence of between-subjects differences between chronic pain patients and healthy control subjects.

Sleep, Positive Affect, and Circulating Interleukin-6 in Women With Temporomandibular Joint Disorder.

OBJECTIVE: Systemic inflammation is commonly observed in idiopathic chronic pain conditions, including temporomandibular joint disorder (TMD). Trait positive affect (PA) is associated with lower inflammation in healthy controls, but those effects may be threatened by poor sleep. The associations between PA with proinflammatory cytokine activity and potential moderation by sleep in chronic pain are not known. We thus investigated the association between PA and circulating interleukin-6 (IL-6) and moderation of that association by sleep in a sample of women with TMD and sleep difficulties. METHODS: Participants (n = 110) completed the insomnia severity index and provided blood samples at five intervals throughout an evoked pain testing session. They then completed a 14-day diary assessing sleep and affect, along with wrist actigraphy. RESULTS: There was not a significant main effect of PA on resting or pain-evoked IL-6 (b = 0.04, p = .33). Diary total sleep time (b = -0.002, p = .008), sleep efficiency (b = -0.01, p = .005), sleep onset latency (b = 0.006, p = .010), and wake after sleep onset (b = 0.003, p = .033) interacted with PA to predict IL-6, such that PA inversely predicted IL-6 at higher levels of total sleep time and sleep efficiency and at lower levels of sleep onset latency and wake after sleep onset. Surprisingly, when sleep was poor, PA predicted greater IL-6. CONCLUSIONS: The potential salutary effects of PA on resting IL-6 erode when sleep is poor, underscoring the importance of considering sleep in conceptual and intervention models of TMD.

Insomnia with objective short sleep duration in women with temporomandibular joint disorder: quantitative sensory testing, inflammation and clinical pain profiles.

OBJECTIVES/BACKGROUND: Temporomandibular joint disorder (TMD) is a disabling facial pain syndrome with a high prevalence of insomnia that primarily affects women. Insomnia with objective short sleep duration (ISSD) is an emerging phenotype linked to cardiometabolic morbidity and increased mortality. The present report examines the association of ISSD on clinical and laboratory pain and systemic inflammation in TMD. METHODS: We collected baseline data from 128 women with TMD and insomnia as part of a clinical trial evaluating psychological interventions for sleep and pain. Participants completed self-report questionnaires, one-night polysomnography, a two-week actigraphy assessment, quantitative sensory testing (QST) to assess cold pain tolerance, pain sensitivity and central sensitization and circulating Interleukin-6 levels were measured to assess systemic inflammation. RESULTS: 24.2% (n = 31) of the sample met criteria for ISSD [polysomnography (sleep duration <6 h)]. Compared to those with insomnia and normal sleep duration, ISSD were older (40.4 vs. 34.9,p < 0.05) and a greater proportion self-identified as Black (48.4% vs 11.3%,p < 0.001). Multivariate regressions revealed that ISSD endorsed higher self-report pain severity and functional limitation of the jaw. ISSD also demonstrated increased generalized pain sensitivity, enhanced central sensitization, cold pressor tolerance and higher resting interleukin-6 levels. CONCLUSIONS: This is the first study to characterize the ISSD phenotype in a chronic pain sample and expand the scope of its negative health outcomes to chronic pain. ISSD may be an important chronic pain phenotype associated with a more severe clinical and laboratory pain profile, and future studies should focus on implications for treatment response and disease trajectory. CLINICAL TRIAL: ClinicalTrials.gov Identifier: NCT01794624.

Enhanced mindfulness-based stress reduction in episodic migraine-effects on sleep quality, anxiety, stress, and depression: a secondary analysis of a randomized clinical trial.

ABSTRACT: Patients with migraine suffer from high morbidity related to the repeated headache attacks, characteristic of the disorder, poor sleep, and a high prevalence of comorbid psychosocial disorders. Current pharmacological therapies do not address these aspects of migraine, but nonpharmacological treatments such as mindfulness-based stress reduction (MBSR) have been shown to improve both pain and psychological well-being. In this secondary analysis, we examined the change over time in sleep quality and psychosocial outcomes from the magnetic resonance imaging outcomes for mindfulness meditation clinical trial and assessed how these mediated treatment response (50% reduction in headache frequency postintervention). We also examined the relationship between baseline values and treatment response. The trial (primary outcomes previously reported) included 98 patients with episodic migraine randomized to either enhanced MBSR (MBSR+) or stress management for headache. They completed psychosocial questionnaires and headache diaries at baseline (preintervention), midintervention (10 weeks after baseline), and postintervention (20 weeks after baseline). There was a significant improvement in sleep quality from baseline to postintervention (P = 0.0025) in both groups. There were no significant changes from baseline or between groups in anxiety, depression, and stress. There was also no significant association between baseline scores and treatment response. Mediation analysis showed a significant indirect effect of 6% for sleep: In other words, small improvements in sleep may have contributed to the efficacy of MBSR+.Trial registration: NCT02133209.

Pain Expectancy and Positive Affect Mediate the day-to-day Association Between Objectively Measured Sleep and Pain Severity Among Women With Temporomandibular Disorder.

The majority of individuals with temporomandibular disorders (TMD) experience sleep disturbance, which can maintain and exacerbate chronic pain. However, the factors underlying the sleep-pain link have not been fully elucidated, especially beyond the laboratory. Sleep deprivation can induce threat interpretation bias, as well as impairment in positive affective functioning. Using both actigraphy and daily diaries, we examined whether morning pain expectancy and positive affect mediate the association between previous night's sleep disturbance and next-day overall pain severity. Total sleep time (TST) was selected as the primary measure of sleep. The sample included 144 women (mean age = 36 [SD = 11.1]) with TMD who displayed at least subclinical insomnia. Sleep was assessed for 14 days using actigraphy which was validated by concurrent sleep diaries. Daily diary assessments of pain-related experiences and affective states were conducted twice per day (ie, once upon participants' waking and the other prior to going to sleep) for the same 14-day period. Multilevel structural equation modeling revealed that both morning pain expectancy (95% CI: -.0004, -.00003) and positive affect (95% CI: -.0005, -.000001) mediated the association between previous night's TST and next-day's overall pain severity, such that shorter previous night TST was associated with higher next-morning pain expectancy and lower positive affect, which in turn were associated with a greater level of next-day's overall pain severity while controlling for morning pain severity. Reducing exaggerated daily pain expectancy and up-regulating positive affect may be important intervention targets for disengaging the sleep-pain link among individuals with co-occurring TMD and sleep disturbance. PERSPECTIVE: The daily link between previous night sleep duration and next day pain severity is mediated by morning pain expectancy and positive affect among women with temporomandibular disorder and sleep disturbance. Reducing pain expectancy and increasing positive affect may serve an important role in improving self-management of chronic pain.

Differences in gray matter volume in episodic migraine patients with and without prior diagnosis or clinical care: a cross-sectional study.

BACKGROUND: Migraine sufferers face difficulties getting appropriate care and treatment. Migraine is associated with reduced gray matter volume (GMV) in several brain regions, which could be related to various clinical characteristics of the disorder. OBJECTIVES: To examine differences in GMV in migraine patients with and without prior clinical care for migraine and examine differences in migraine clinical variables, psychosocial symptoms and their relationship with GMV. METHODS: We utilized the baseline MRI scan and psychosocial symptom questionnaires from a longitudinal randomized controlled trial. Prior care of migraine was determined by diagnosis by a medical practitioner or prescription of migraine specific medication. RESULTS: 117 patients were included in the study. Patients without prior care (n=23) had reduced GMV in the right dorsal medial prefrontal cortex (dMPFC) relative to patients who had prior care (p=0.034, FWE corrected). Both patient groups had reduced GMV compared to healthy controls (n=36). Patient groups did not differ in headache clinical variables. Regardless of care status, increasing scores on the stress (Perceived Stress Score) and depression questionnaires (Patient Health Questionnaire) were associated with increased GMV in the dMPFC. CONCLUSIONS: Clinical care may impact GMV in migraine patients. Patients may need different treatment options to address this baseline deficit. TRIAL REGISTRATION: NCT02133209.