Enhanced motor network engagement during reward gain anticipation in fibromyalgia.

Reward motivation is essential in shaping human behavior and cognition. Both reward motivation and reward brain circuits are altered in chronic pain conditions, including fibromyalgia. In this study of fibromyalgia patients, we used a data-driven independent component analysis (ICA) approach to investigate how brain networks contribute to altered reward processing. From females with fibromyalgia (N = 24) and female healthy controls (N = 24), we acquired fMRI data while participants performed a monetary incentive delay (MID) reward task. After analyzing the task-based fMRI data using ICA to identify networks, we analyzed 3 networks of interest: motor network (left), value-driven attention network, and basal ganglia network. Then, we evaluated correlation coefficients between each network timecourse versus a task-based timecourse which modeled gain anticipation. Compared to controls, the fibromyalgia cohort demonstrated significantly stronger correlation between the left motor network timecourse and the gain anticipation timecourse, indicating the left motor network was more engaged with gain anticipation in fibromyalgia. In an exploratory analysis, we compared motor network engagement during early versus late phases of gain anticipation. Across cohorts, greater motor network engagement (i.e., stronger correlation between network and gain anticipation) occurred during the late timepoint, which reflected enhanced motor preparation immediately prior to response. Consistent with the main results, patients exhibited greater engagement of the motor network during both early and late phases compared with healthy controls. Visual-attention and basal ganglia networks revealed similar engagement in the task across groups. As indicated by post-hoc analyses, motor network engagement was positively related to anxiety and negatively related to reward responsiveness. In summary, we identified enhanced reward-task related engagement of the motor network in fibromyalgia using a novel data-driven ICA approach. Enhanced motor network engagement in fibromyalgia may relate to impaired reward motivation, heightened anxiety, and possibly to altered motor processing, such as restricted movement or dysregulated motor planning.

Interplay between noxious heat sensitivity and temporal summation magnitude in patients with fibromyalgia and long-term opioid use.

Introduction: In chronic pain conditions such as fibromyalgia (FM), pain amplification within the central nervous system, or "central sensitization," may contribute to the development and maintenance of chronic pain. Chronic pain treatments include opioid therapy, and opioid therapy may maladaptively increase central sensitization, particularly in patients who take opioids long-term. However, it has remained unknown how central sensitization is impacted in patients who use opioids long-term. Methods: To investigate how long-term opioid therapy affects central sensitization, we used the validated measure of temporal summation. The temporal summation measurement consists of applying a series of noxious stimuli to a patient's skin and then calculating changes in the patient's pain rating to each stimulus. Using this measurement, we evaluated temporal summation in study participants with fibromyalgia who take opioids long-term (i.e., greater than 90 days duration; n = 24, opioid-FM). We compared opioid-FM responses to 2 control groups: participants with fibromyalgia who do not take opioids (n = 33, non-opioid FM), and healthy controls (n = 31). For the temporal summation measurement, we applied a series of 10 noxious heat stimuli (sensitivity-adjusted temperatures) to the ventral forearm (2s duration of each stimulus, applied once every 3 s). Additionally, we collected responses to standard pain and cognitive-affective questionnaires to assess pain severity and other factors. Results and discussion: Group differences in sensitivity-adjusted stimulus temperatures were observed, with only the non-opioid FM group requiring significantly lower stimulus temperatures (The opioid-FM group also required lower temperatures, but not significantly different from the control group). However, all 3 groups exhibited similar magnitudes of temporal summation. Across combined FM groups, temporal summation negatively correlated with pain severity (r = -0.31, p = 0.021). Within the opioid-FM group, higher pain sensitivity to heat (i.e., lower sensitivity-adjusted temperatures) showed a trend relationship with higher opioid dosage (r = -0.45, p = 0.036), potentially reflective of opioid-related hyperalgesia. Our findings also indicated that heightened pain severity may skew sensitivity-adjusted temporal summation, thereby limiting its utility for measuring central sensitization. Overall, in participants taking opioids, temporal summation may be influenced by hypersensitivity to heat pain, which appeared to vary with opioid dosage.

Reduced Spinal Cord Gray Matter in Patients with Fibromyalgia Using Opioids Long-term.

Objective: Chronic pain involves alterations in brain gray matter volume (GMV). Moreover, opioid medications are known to reduce GMV in numerous brain regions involved in pain processing. However, no research has evaluated (1) chronic pain-related GMV alterations in the spinal cord or (2) the effect of opioids on spinal cord GMV. Accordingly, this study evaluated spinal cord GMV in health controls and patients with fibromyalgia who were using and not using opioids long-term. Methods: We analyzed average C5 - C7 GMV of the spinal cord dorsal and ventral horns in separate female cohorts of healthy controls (HC, n = 30), fibromyalgia patients not using opioids (FMN, n = 31), and fibromyalgia patients using opioids long-term (FMO, n = 27). To assess the effect of group on average dorsal and ventral horn GMV, we conducted a one-way multivariate analysis of covariance. Results: After controlling for age, we observed a significant effect of group on ventral horn GMV (p = 0.03, η2 = 0.09), and on dorsal horn GMV (p = 0.05, η2 = 0.08). Tukey's posthoc comparisons showed that, compared to HC participants, FMOs had significantly lower ventral (p = 0.01) and dorsal (p = 0.02) GMVs. Among FMOs only, ventral horn GMV was significantly positively associated with pain severity and interference, and both dorsal and ventral GMVs were significantly positively associated with cold pain tolerance. Conclusion: Long-term opioid use may impact sensory processing in fibromyalgia via gray matter changes within the cervical spinal cord.

Altered Functional Networks during Gain Anticipation in Fibromyalgia.

Reward motivation is essential in shaping human behavior and cognition. Previous studies have shown altered reward motivation and reward brain circuitry in chronic pain conditions, including fibromyalgia. Fibromyalgia is a chronic disorder characterized by widespread musculoskeletal pain, fatigue, cognitive problems, and mood-related symptoms. In this study, we analyzed brain reward networks in patients with fibromyalgia by using a data-driven approach with task-based fMRI data. fMRI data from 24 patients with fibromyalgia and 24 healthy controls were acquired while subjects performed a monetary incentive delay (MID) reward task. Functional networks were derived using independent component analysis (ICA) focused on the gain anticipation phase of the reward task. Functional activity in the motor, value-driven attention, and basal ganglia networks was evaluated during gain anticipation in both patient and healthy control groups. Compared to controls, the motor network was more engaged during gain anticipation in patients with fibromyalgia. Our findings suggest that reward motivation may lead to hyperactivity in the motor network, possibly related to altered motor processing, such as restricted movement or dysregulated motor planning in fibromyalgia. As an exploratory analysis, we compared levels of motor network engagement during early and late timepoints of the gain anticipation phase. Both groups showed greater motor network engagement during the late timepoint (i.e., closer to response), which reflected motor preparation prior to target response. Importantly, compared to controls and consistent with the initial findings described above, patients exhibited greater engagement of the motor network during both early and late timepoints. In summary, by using a novel data-driven ICA approach to analyze task-based fMRI data, we identified elevated motor network engagement during gain anticipation in fibromyalgia.

Altered resting-state functional connectivity within corticostriatal and subcortical-striatal circuits in chronic pain.

Brain corticostriatal circuits are important for understanding chronic pain and highly relevant to motivation and cognitive processes. It has been demonstrated that in patients with chronic back pain, altered nucleus accumbens (NAcc)-medial prefrontal cortex (MPFC) circuit fMRI-based activity is predictive of patient outcome. We evaluated the NAcc-MPFC circuit in patients with another chronic pain condition, fibromyalgia, to extend these important findings. First, we compared fMRI-based NAcc-MPFC resting-state functional connectivity in patients with fibromyalgia (N = 32) vs. healthy controls (N = 37). Compared to controls, the NAcc-MPFC circuit's connectivity was significantly reduced in fibromyalgia. In addition, within the fibromyalgia group, NAcc-MPFC connectivity was significantly correlated with trait anxiety. Our expanded connectivity analysis of the NAcc to subcortical brain regions showed reduced connectivity of the right NAcc with mesolimbic circuit regions (putamen, thalamus, and ventral pallidum) in fibromyalgia. Lastly, in an exploratory analysis comparing our fibromyalgia and healthy control cohorts to a separate publicly available dataset from patients with chronic back pain, we identified reduced NAcc-MPFC connectivity across both the patient groups with unique alterations in NAcc-mesolimbic connectivity. Together, expanding upon prior observed alterations in brain corticostriatal circuits, our results provide novel evidence of altered corticostriatal and mesolimbic circuits in chronic pain.

Altered Reward Processing and Sex Differences in Chronic Pain.

Chronic pain and reward processing are understood to be reciprocally related to one another. Previous studies of reward processing in chronic pain patients have reported incongruent findings. While several factors likely contribute to these disparate findings, these previous studies did not stratify their analyses by sex-a factor previously shown to robustly impact reward-related responses. Thus, we examined sex as a factor of interest in level of striatal activation during anticipation of monetary incentives among patients with chronic non-specific back pain and healthy controls (HC). This study utilized functional magnetic resonance imaging during a monetary incentive delay task to evaluate reward and loss responsivity in the striatum among males and females with and without chronic pain (N = 90). Group, sex, and group-by-sex interactions were analyzed via repeated measures analysis of variance. Among HC, males exhibited significantly greater blood oxygen level dependent (BOLD) signal in the striatum during reward anticipation, particularly during large reward trials. By contrast, no significant sex differences were observed among patients. A significant group-by-sex interaction was also observed, revealing diminished BOLD responses among males with chronic pain relative to control males. These results provide novel evidence of sex-specific reductions in anticipatory responses to reward in patients with chronic pain. Altered striatal reward responsivity among males, but not females, suggests that the reward systems of males and females are uniquely disrupted by chronic pain, and highlights the value of including sex as a factor of interest in future studies of reward responsivity in the context of persistent pain.

Unique and joint associations of polygenic risk for major depression and opioid use disorder with endogenous opioid system function.

Major depressive disorder (MDD) and opioid use disorder (OUD) are common, potentially fatal, polygenic disorders that are moderately heritable and often co-occur. We examined the unique and shared associations of polygenic risk scores (PRS) for these disorders with µ-opioid receptor (MOR) concentration and endogenous opioid response during a stressful stimulus. Participants were 144 healthy European-ancestry (EA) subjects (88 females) who underwent MOR quantification scans with [11C]carfentanil and PET and provided DNA for genotyping. MOR non-displaceable binding potential (BPND) was measured in 5 regions of interest (ROIs) related to mood and addiction. We examined associations of PRS both at baseline and following opioid release calculated as the ratio of baseline and stress-challenge scans, first in the entire sample and then separately by sex. MOR availability at baseline was positively associated with MDD PRS in the amygdala and ventral pallidum. MDD and OUD PRS were significantly associated with stress-induced opioid system activation in multiple ROIs, accounting for up to 14.5% and 5.4%, respectively, of the variance in regional activation. The associations were most robust among females, where combined they accounted for up to 25.0% of the variance among the ROIs. We conclude that there is a pathophysiologic link between polygenic risk for MDD and OUD and opioid system activity, as evidenced by PRS with unique and overlapping regional associations with this neurotransmitter system. This link could help to explain the high rate of comorbidity of MDD and OUD and suggests that opioid-modulating interventions could be useful in treating MDD and OUD, both individually and jointly.

Mindfulness-Oriented Recovery Enhancement vs Supportive Group Therapy for Co-occurring Opioid Misuse and Chronic Pain in Primary Care: A Randomized Clinical Trial.

IMPORTANCE: Successful treatment of opioid misuse among people with chronic pain has proven elusive. Guidelines recommend nonopioid therapies, but the efficacy of mindfulness-based interventions for opioid misuse is uncertain. OBJECTIVE: To evaluate the efficacy of Mindfulness-Oriented Recovery Enhancement (MORE) for the reduction of opioid misuse and chronic pain. DESIGN, SETTING, AND PARTICIPANTS: This interviewer-blinded randomized clinical trial enrolled patients from primary care clinics in Utah between January 4, 2016, and January 16, 2020. The study included 250 adults with chronic pain receiving long-term opioid therapy who were misusing opioid medications. INTERVENTIONS: Treatment with MORE (comprising training in mindfulness, reappraisal, and savoring positive experiences) or supportive group psychotherapy (control condition) across 8 weekly 2-hour group sessions. MAIN OUTCOMES AND MEASURES: Primary outcomes were (1) opioid misuse assessed by the Drug Misuse Index (self-report, interview, and urine screen) and (2) pain severity and pain-related functional interference, assessed by subscale scores on the Brief Pain Inventory through 9 months of follow-up. Secondary outcomes were opioid dose, emotional distress, and ecological momentary assessments of opioid craving. The minimum intervention dose was defined as 4 or more completed sessions of MORE or supportive group psychotherapy. RESULTS: Among 250 participants (159 women [63.6%]; mean [SD] age, 51.8 [11.9] years), 129 were randomized to the MORE group and 121 to the supportive psychotherapy group. Overall, 17 participants (6.8%) were Hispanic or Latino, 218 (87.2%) were White, and 15 (6.0%) were of other races and/or ethnicities (2 American Indian, 3 Asian, 1 Black, 2 Pacific Islander, and 7 did not specify). At baseline, the mean duration of pain was 14.7 years (range, 1-60 years), and the mean (SD) morphine-equivalent opioid dose was 101.0 (266.3) mg (IQR, 16.0-90.0 mg). A total of 203 participants (81.2%) received the minimum intervention dose (mean [SD], 5.7 [2.2] sessions); at 9 months, 92 of 250 participants (36.8%) discontinued the study. The overall odds ratio for reduction in opioid misuse through the 9-month follow-up period in the MORE group compared with the supportive psychotherapy group was 2.06 (95% CI, 1.17-3.61; P = .01). At 9 months, 36 of 80 participants (45.0%) in the MORE group were no longer misusing opioids compared with 19 of 78 participants (24.4%) in the supportive psychotherapy group. Mixed models demonstrated that MORE was superior to supportive psychotherapy through 9 months of follow-up for pain severity (between-group effect: 0.49; 95% CI, 0.17-0.81; P = .003) and pain-related functional interference (between-group effect: 1.07; 95% CI, 0.64-1.50; P < .001). Participants in the MORE group reduced their opioid dose to a greater extent than those in the supportive psychotherapy group. The MORE group also had lower emotional distress and opioid craving. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, among adult participants in a primary care setting, the MORE intervention led to sustained improvements in opioid misuse and chronic pain symptoms and reductions in opioid dosing, emotional distress, and opioid craving compared with supportive group psychotherapy. Despite attrition caused by the COVID-19 pandemic and the vulnerability of the sample, MORE appeared to be efficacious for reducing opioid misuse among adults with chronic pain. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02602535.

Risk for opioid misuse in chronic pain patients is associated with endogenous opioid system dysregulation.

µ-Opioid receptors (MOR) are a major target of endogenous and exogenous opioids, including opioid pain medications. The µ-opioid neurotransmitter system is heavily implicated in the pathophysiology of chronic pain and opioid use disorder and, as such, central measures of µ-opioid system functioning are increasingly being considered as putative biomarkers for risk to misuse opioids. To explore the relationship between MOR system function and risk for opioid misuse, 28 subjects with chronic nonspecific back pain completed a clinically validated measure of opioid misuse risk, the Pain Medication Questionnaire (PMQ), and were subsequently separated into high (PMQ > 21) and low (PMQ ≤ 21) opioid misuse risk groups. Chronic pain patients along with 15 control participants underwent two separate [11C]-carfentanil positron emission tomography scans to explore MOR functional measures: one at baseline and one during a sustained pain-stress challenge, with the difference between the two providing an indirect measure of stress-induced endogenous opioid release. We found that chronic pain participants at high risk for opioid misuse displayed higher baseline MOR availability within the right amygdala relative to those at low risk. By contrast, patients at low risk for opioid misuse showed less pain-induced activation of MOR-mediated, endogenous opioid neurotransmission in the nucleus accumbens. This study links human in vivo MOR system functional measures to the development of addictive disorders and provides novel evidence that MORs and µ-opioid system responsivity may underlie risk to misuse opioids among chronic pain patients.

Replication of neural responses to monetary incentives and exploration of reward-influenced network connectivity in fibromyalgia.

Neuroimaging research has begun to implicate alterations of brain reward systems in chronic pain. Previously, using functional magnetic resonance imaging (fMRI) and a monetary incentive delay (MID) task, Martucci et al. (2018) showed that neural responses to reward anticipation and outcome are altered in fibromyalgia. In the present study, we aimed to test the replicability of these altered neural responses to reward in a separate fibromyalgia cohort. In addition, the present study was conducted at a distinct U.S. location but involved a similar study design. For the present study, 20 patients with fibromyalgia and 20 healthy controls participated in MID task fMRI scan procedures and completed clinical/psychological questionnaires. fMRI analyses comparing patient and control groups revealed a consistent trend of main results which were largely similar to the prior reported results. Specifically, in the replication fibromyalgia cohort, medial prefrontal cortex (MPFC) response was reduced during gain anticipation and was increased during no-loss (non-punishment) outcome compared to controls. Also consistent with previous findings, the nucleus accumbens response to gain anticipation did not differ in patients vs. controls. Further, results from similarly-designed behavioral, correlational, and exploratory analyses were complementary to previous findings. Finally, a novel network-based functional connectivity analysis of the MID task fMRI data across patients vs. controls implied enhanced connectivity within the default mode network in participants with fibromyalgia. Together, based on replicating prior univariate results and new network-based functional connectivity analyses of MID task fMRI data, we provide further evidence of altered brain reward responses, particularly in the MPFC response to reward outcomes, in patients with fibromyalgia.

Mindfulness-oriented recovery enhancement reduces opioid misuse risk via analgesic and positive psychological mechanisms: A randomized controlled trial.

OBJECTIVE: Despite the heightened urgency of the current prescription opioid crisis, few psychotherapies have been evaluated for chronic pain patients receiving long-term opioid analgesics. Current psychological pain treatments focus primarily on ameliorating negative affective processes, yet basic science suggests that risk for opioid misuse is linked with a dearth of positive affect. Interventions that modulate positive psychological processes may produce therapeutic benefits among patients with opioid-treated chronic pain. The aim of this study was to conduct a theory-driven mechanistic analysis of proximal outcome data from a Stage 2 randomized controlled trial of Mindfulness-Oriented Recovery Enhancement (MORE), an integrative intervention designed to promote positive psychological health. METHOD: Patients with opioid-treated chronic pain (N = 95; age = 56.8 ± 11.7; 66% female) were randomized to 8 weeks of therapist-led MORE or support group (SG) interventions. A latent positive psychological health variable comprised of positive affect, meaning in life, and self-transcendence measures was examined as a mediator of the effect of MORE on changes in pain severity at posttreatment and opioid misuse risk by 3-month follow-up. RESULTS: Participants in MORE reported significantly greater reductions in pain severity by posttreatment (p = .03) and opioid misuse risk by 3-month follow-up (p = .03) and significantly greater increases in positive psychological health (p < .001) than SG participants. Increases in positive psychological health mediated the effect of MORE on pain severity by posttreatment (p = .048), which in turn predicted decreases in opioid misuse risk by follow-up (p = .02). CONCLUSIONS: Targeting positive psychological mechanisms via MORE and other psychological interventions may reduce opioid misuse risk among chronic pain patients receiving long-term opioid therapy. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Adverse childhood experiences predict autonomic indices of emotion dysregulation and negative emotional cue-elicited craving among female opioid-treated chronic pain patients.

Through autonomic and affective mechanisms, adverse childhood experiences (ACEs) may disrupt the capacity to regulate negative emotions, increasing craving and exacerbating risk for opioid use disorder (OUD) among individuals with chronic pain who are receiving long-term opioid analgesic pharmacotherapy. This study examined associations between ACEs, heart rate variability (HRV) during emotion regulation, and negative emotional cue-elicited craving among a sample of female opioid-treated chronic pain patients at risk for OUD. A sample of women (N = 36, mean age = 51.2 ± 9.5) with chronic pain receiving long-term opioid analgesic pharmacotherapy (mean morphine equivalent daily dose = 87.1 ± 106.9 mg) were recruited from primary care and pain clinics to complete a randomized task in which they viewed and reappraised negative affective stimuli while HRV and craving were assessed. Both ACEs and duration of opioid use significantly predicted blunted HRV during negative emotion regulation and increased negative emotional cue-elicited craving. Analysis of study findings from a multiple-levels-of-analysis approach suggest that exposure to childhood abuse occasions later emotion dysregulation and appetitive responding toward opioids in negative affective contexts among adult women with chronic pain, and thus this vulnerable clinical population should be assessed for OUD risk when initiating a course of extended, high-dose opioids for pain management.

Autonomic and affective mediators of the relationship between mindfulness and opioid craving among chronic pain patients.

Prescription opioid misuse among chronic pain patients is undergirded by self-regulatory deficits, affective distress, and opioid-cue reactivity. Dispositional mindfulness has been associated with enhanced self-regulation, lower distress, and adaptive autonomic responses following drug-cue exposure. We hypothesized that dispositional mindfulness might serve as a protective factor among opioid-treated chronic pain patients. We examined heart-rate variability (HRV) during exposure to opioid cues and depressed mood as mediators of the association between dispositional mindfulness and opioid craving. Data were obtained from a sample of chronic pain patients (N = 115) receiving long-term opioid pharmacotherapy. Participants self-reported opioid craving and depression, and HRV was measured during an opioid-cue dot-probe task. Dispositional mindfulness was significantly positively correlated with HRV, and HRV was significantly inversely associated with opioid craving. Dispositional mindfulness was significantly negatively correlated with depression, and depression was significantly positively correlated with opioid craving. Path analysis revealed significant indirect effects of dispositional mindfulness on craving through both HRV and depression. Dispositional mindfulness may buffer against opioid craving among chronic pain patients prescribed opioids; this buffering effect may be a function of improved autonomic and affective responses. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The Mindful Personality II: Exploring the Metatraits from a Cybernetic Perspective.

Relationships between dispositional mindfulness and the personality metatraits, stability and plasticity, remain unexplored despite continued efforts to more accurately characterize associations between dispositional mindfulness and personality. The metatraits are theorized to constitute basic requirements for biological survival and their expression is believed to be a strong determinant of well-being. As such, this study used path analysis to explore associations between dispositional mindfulness, the metatraits and psychological well-being in a sample of 403 American adults. Results indicate that dispositional mindfulness is principally associated with stability, or the capacity to sustain currently operative schemas and goals. Results further suggest a positive relationship between dispositional mindfulness and plasticity, or the tendency to flexibly adapt to changing circumstances. A more granular investigation of these associations demonstrated that the facets of dispositional mindfulness are differentially related with the metatraits. Ultimately, the metatraits were found to fully mediate the relationship between dispositional mindfulness and psychological well-being.

Dispositional mindfulness and prescription opioid misuse among chronic pain patients: Craving and attention to positive information as mediating mechanisms.

OBJECTIVES: Opioid-treated chronic pain patients may be at risk for prescription opioid misuse due to heightened opioid craving coupled with deficits in attention to naturally rewarding, positive stimuli. Conversely, dispositional mindfulness, which is associated with reduced craving and increased responsiveness to natural rewards, may serve as a protective factor and buffer opioid misuse risk. The current investigation aimed to examine the association between mindfulness and opioid misuse, and to test opioid craving and attention to positive information as mediators of this relationship. METHODS: This cross-sectional analysis examined data obtained from a sample of civilian opioid-treated chronic pain patients in the Southeastern U.S. (Sample 1: N = 115), as well as civilian (Sample 2: N = 141) and military samples in the Intermountain West (Sample 3: N = 44). Pearson correlations and path analyses were employed to test relations among participant self-reports on the Current Opioid Misuse Measure (COMM), the Five Facet Mindfulness Questionnaire (FFMQ), two measures of opioid craving, and the Attention to Positive and Negative Information Scale (APNIS). RESULTS: Across all three samples, dispositional mindfulness was significantly inversely associated with opioid misuse (N = 300, r = -0.36, p < .001). Reduced opioid craving and increased attention to positive information mediated the association between dispositional mindfulness and opioid misuse. DISCUSSION: Dispositional mindfulness may buffer opioid misuse risk by attenuating opioid craving and enhancing attention to naturally rewarding stimuli.

Self-interest may not be entirely in the interest of the self: Association between selflessness, dispositional mindfulness and psychological well-being.

The association between mindfulness and selflessness is firmly grounded in classical Indo-Sino-Tibetan contemplative traditions, but has received limited empirical attention from Western researchers. In Buddhism, the relationship between mindfulness and the self is of central concern to the cultivation of well-being. Mindfulness is believed to encourage insight into the truly insubstantial nature of the self, an understanding that is thought to encourage well-being. The present study explores these relationships, attending to dispositional mindfulness, the self as it exists on a continuum from self-centered to selfless, and psychological well-being. Results indicate a positive relationship between selflessness, dispositional mindfulness, and psychological well-being. It appears that construing the self as interdependent and interconnected with a broader social, natural, and cosmic context is linked with greater psychological well-being and dispositional mindfulness. Path analyses revealed that selflessness mediated the relationship between dispositional mindfulness and psychological well-being.

Biobehavioral Mechanisms of Mindfulness as a Treatment for Chronic Stress: An RDoC Perspective.

Mindfulness-based interventions have been heralded as promising means of alleviating chronic stress. While meta-analyses indicate that mindfulness-based interventions significantly reduce global measures of stress, how mindfulness-based interventions modulate the specific mechanisms underpinning chronic stress as operationalized by the National Institute of Mental Health research domain criteria (RDoC) of sustained threat has not yet been detailed in the literature. To address this knowledge gap, this article aims to (1) review evidence that mindfulness-based interventions ameliorate each of the 10 elements of behavioral dysregulation characterizing sustained threat via an array of mindful counter-regulatory strategies; (2) review evidence that mindfulness-based interventions modify biological domains implicated in sustained threat, such as the hypothalamic-pituitary-adrenal axis, as well as brain circuits involved in attentional function, limbic reactivity, habit behavior, and the default mode network; and (3) integrate these findings into a novel conceptual framework of mindful self-regulation in the face of stress-the Mindfulness-to-Meaning Theory. Taken together, the extant body of scientific evidence suggests that the practice of mindfulness enhances a range biobehavioral factors implicated in adaptive stress coping and induces self-referential plasticity, leading to the ability to find meaning in adversity. These mechanistic findings can inform the treatment development process to optimize the next generation of mindfulness-based interventions for greater therapeutic efficacy.

Randomized Controlled Trial of Brief Mindfulness Training and Hypnotic Suggestion for Acute Pain Relief in the Hospital Setting.

BACKGROUND: Medical management of acute pain among hospital inpatients may be enhanced by mind-body interventions. OBJECTIVE: We hypothesized that a single, scripted session of mindfulness training focused on acceptance of pain or hypnotic suggestion focused on changing pain sensations through imagery would significantly reduce acute pain intensity and unpleasantness compared to a psychoeducation pain coping control. We also hypothesized that mindfulness and suggestion would produce significant improvements in secondary outcomes including relaxation, pleasant body sensations, anxiety, and desire for opioids, compared to the control condition. METHODS: This three-arm, parallel-group randomized controlled trial conducted at a university-based hospital examined the acute effects of 15-min psychosocial interventions (mindfulness, hypnotic suggestion, psychoeducation) on adult inpatients reporting "intolerable pain" or "inadequate pain control." Participants (N = 244) were assigned to one of three intervention conditions: mindfulness (n = 86), suggestion (n = 73), or psychoeducation (n = 85). KEY RESULTS: Participants in the mind-body interventions reported significantly lower baseline-adjusted pain intensity post-intervention than those assigned to psychoeducation (p < 0.001, percentage pain reduction: mindfulness = 23%, suggestion = 29%, education = 9%), and lower baseline-adjusted pain unpleasantness (p < 0.001). Intervention conditions differed significantly with regard to relaxation (p < 0.001), pleasurable body sensations (p = 0.001), and desire for opioids (p = 0.015), but all three interventions were associated with a significant reduction in anxiety (p < 0.001). CONCLUSIONS: Brief, single-session mind-body interventions delivered by hospital social workers led to clinically significant improvements in pain and related outcomes, suggesting that such interventions may be useful adjuncts to medical pain management. TRIAL REGISTRATION: Trial Registry: ClinicalTrials.gov ; registration ID number: NCT02590029 URL: https://clinicaltrials.gov/ct2/show/NCT02590029.