Exploring the effects of fitbit incentive on treatment outcomes in veterans undergoing intensive pain rehabilitation program.

OBJECTIVE: This study compares clinical pain outcomes between patients in a pain treatment program that received a Fitbit, to patients that did not. We also explored: (1) cognitive, emotional, and psychological factors that may have impacted the decision to opt in to receiving a Fitbit; and (2) whether the choice to receive a Fitbit impacted changes in cognitive, emotional, and psychological factors following treatment. METHODS: Among 58 patients in a multidisciplinary pain treatment program at a Veterans Affairs Healthcare System hospital, 31 patients opted to receive a Fitbit as adjunct treatment, while 27 did not. This study utilized patient-reported and practitioner-collected data from the pain treatment program. RESULTS: Compared to the non-Fitbit group, the Fitbit group displayed a significant decrease in average pain intensity, however showed no correlation between Fitbit activity and average pain intensity. Additionally, treatment satisfaction was the only predictor of treatment group, when modeling pre- and post-treatment outcomes changes. CONCLUSION: The implementation of a Fitbit may lead to improved pain intensity. Initial evidence suggests that opting to receive a Fitbit during a pain treatment program indicates treatment engagement leading to greater treatment satisfaction. Future work is needed to verify and expand upon this potential mechanism.

Identification of group differences in predictive anticipatory biasing of pain during uncertainty: preparing for the worst but hoping for the best.

ABSTRACT: Pain anticipation during conditions of uncertainty can unveil intrinsic biases, and understanding these biases can guide pain treatment interventions. This study used machine learning and functional magnetic resonance imaging to predict anticipatory responses in a pain anticipation experiment. One hundred forty-seven participants that included healthy controls (n = 57) and individuals with current and/or past mental health diagnosis (n = 90) received cues indicating upcoming pain stimuli: 2 cues predicted high and low temperatures, while a third cue introduced uncertainty. Accurate differentiation of neural patterns associated with specific anticipatory conditions was observed, involving activation in the anterior short gyrus of the insula and the nucleus accumbens. Three distinct response profiles emerged: subjects with a negative bias towards high pain anticipation, those with a positive bias towards low pain anticipation, and individuals whose predictions during uncertainty were unbiased. These profiles remained stable over one year, were consistent across diagnosed psychopathologies, and correlated with cognitive coping styles and underlying insula anatomy. The findings suggest that individualized and stable pain anticipation occurs in uncertain conditions.

Unsupervised learning for prognostic validity in patients with chronic pain in transdisciplinary pain care.

Chronic pain is not a singular disorder and presents in various forms and phenotypes. Here we show data from a cohort of patients seeking treatment in a transdisciplinary pain clinic. Patients completed a multidimensional patient-reported battery as part of routine initial evaluation at baseline and at each of the four subsequent visits over 1-year follow-up (0, 1, 3, 6, 12 months). The goal of this work was to use unsupervised modeling approach to identify whether patients with chronic pain undergoing transdisciplinary intensive rehabilitation treatment: (1) can be derived based upon self-reported outcome measures at baseline (or before treatment initiation), (2) are clinically validated based on their clinical diagnosis and medication use, and (3) differ in treatment trajectories over 1 year of transdisciplinary treatment. We applied unsupervised clustering on baseline outcomes using nine patient-reported symptoms and examined treatment trajectories. The three-cluster solution was internally validated. Psychiatric diagnosis, chronic back pain-related disability and symptoms severity determined cluster assignment and treatment prognosis. Conversely, clinical pain severity had lesser effect. Furthermore, clusters showed stability over time despite symptoms improvement. The accurate and meaningful subgrouping of the underlying chronic pain phenotypes would greatly enhance treatment and provide personalized and effective pain management.

Pain-related opioidergic and dopaminergic neurotransmission: Dual meta-Analyses of PET radioligand studies.

Molecular mechanisms of the interaction between opioidergic and dopaminergic processing during pain-related experiences in the human brain are still incompletely understood. This is partially due to the invasive nature of the available techniques to visualize and measure metabolic activity. Positron Emission Tomography (PET) radioligand studies using radioactive substances are still the only available modality to date that allows for the investigation of the molecular mechanisms in the human brain. The most commonly studied PET radiotracers are [11C]-carfentanil (CFN) and [11C]- or [18F]-diprenorphine (DPN), which bind to opioid receptors, and [11C]-raclopride (RAC) and [18F]-fallypride (FAL) tracers, which bind to dopamine receptors. The current meta-analysis examines pain-related studies that used aforementioned opioid and dopamine radioligands in an effort to consolidate the available data into the most likely activated regions. Our primary goal was to identify regions of shared opioid/dopamine neurotransmission during pain-related experiences using within-subject approach. Seed-based d Mapping (SDM) analysis of previously published voxel coordinate data showed that opioidergic activations were strongest in the bilateral caudate, thalamus, right putamen, cingulate gyrus, midbrain, inferior frontal gyrus, and left superior temporal gyrus. The dopaminergic studies showed that the bilateral caudate, thalamus, right putamen, cingulate gyrus, and left putamen had the highest activations. We were able to see a clear overlap between opioid and dopamine activations in a majority of the regions during pain-related experiences, though there were some unique areas of dopaminergic activation such as the left putamen. Regions unique to opioidergic activation included the midbrain, inferior frontal gyrus, and left superior temporal gyrus. Here we provide initial evidence for the functional overlap between opioidergic and dopaminergic processing during aversive states in humans.

Learning from addiction: Craving of prescription opioids in chronic pain sufferers.

Prescription opioids are a primary driver of opioid-related deaths. Although craving is a substantial component of OUD, the degree to which craving leads to misuse among chronic pain patients on long-term prescription opioids is unknown. A clear understanding of the factors that lead to misuse in this vulnerable population is needed for the development of safe and effective practices for opioid taper. This narrative review summarizes the relevant literature on the role of craving in addiction and chronic pain through epidemiological and behavioral studies. The first part of this review examines the role of craving in predicting opioid use/misuse in individuals with chronic pain with and without OUD. The second part covers methods on how craving is evaluated experimentally using both subjective and objective measures and provides related findings. The overall goal of this review is to facilitate the development of a population-specific description of craving in those who use opioids to control chronic pain and to describe how it may be mechanistically linked to patterns of opioid (mis)use.

Distal neuropathic pain in HIV is associated with functional connectivity patterns in default mode and salience networks.

HIV-associated distal neuropathic pain (DNP) is one of the most prevalent, disabling, and treatment-resistant complications of HIV, but its biological underpinnings are incompletely understood. While data specific to mechanisms underlying HIV DNP are scarce, functional neuroimaging of chronic pain more broadly implicates the role of altered resting-state functional connectivity within and between salience network (SN) and default mode network (DMN) regions. However, it remains unclear the extent to which HIV DNP is associated with similar alterations in connectivity. The current study aimed to bridge this gap in the literature through examination of resting-state functional connectivity patterns within SN and DMN regions among people with HIV (PWH) with and without DNP. Resting state functional magnetic resonance imaging (rs-fMRI) scans were completed among 62 PWH with HIV-associated peripheral neuropathy, of whom 27 reported current DNP and 35 did not. Using subgrouping group iterative multiple estimation, we compared connectivity patterns in those with current DNP to those without. We observed weaker connectivity between the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) and stronger connectivity between the anterior cingulate cortex (ACC) and thalamus among those reporting DNP. Overall, these findings implicate altered within DMN (i.e., MPFC-PCC) and within SN (i.e., ACC-thalamus) connectivity as potential manifestations of adaptation to pain from neuropathy and/or mechanisms underlying the development/maintenance of DNP. Findings are discussed in the context of differential brain response to pain (i.e., mind wandering, pain aversion, pain facilitation/inhibition) and therapeutic implications.

Understanding Pain and Trauma Symptoms in Veterans From Resting-State Connectivity: Unsupervised Modeling.

Trauma and posttraumatic stress are highly comorbid with chronic pain and are often antecedents to developing chronic pain conditions. Pain and trauma are associated with greater utilization of medical services, greater use of psychiatric medication, and increased total cost of treatment. Despite the high overlap in the clinic, the neural mechanisms of pain and trauma are often studied separately. In this study, resting-state functional magnetic resonance imaging (rs-fMRI) scans were completed among a diagnostically heterogeneous sample of veterans with a range of back pain and trauma symptoms. Using Group Iterative Multiple Model Estimation (GIMME), an effective functional connectivity analysis, we explored an unsupervised model deriving subgroups based on path similarity in a priori defined regions of interest (ROIs) from brain regions implicated in the experience of pain and trauma. Three subgroups were identified by patterns in functional connection and differed significantly on several psychological measures despite similar demographic and diagnostic characteristics. The first subgroup was highly connected overall, was characterized by functional connectivity from the nucleus accumbens (NAc), the anterior cingulate cortex (ACC), and the posterior cingulate cortex (PCC) to the insula and scored low on pain and trauma symptoms. The second subgroup did not significantly differ from the first subgroup on pain and trauma measures but was characterized by functional connectivity from the ACC and NAc to the thalamus and from ACC to PCC. The third subgroup was characterized by functional connectivity from the thalamus and PCC to NAc and scored high on pain and trauma symptoms. Our results suggest that, despite demographic and diagnostic similarities, there may be neurobiologically dissociable biotypes with different mechanisms for managing pain and trauma. These findings may have implications for the determination of appropriate biotype-specific interventions that target these neurological systems.

Craving of prescription opioids among veterans with chronic pain.

ABSTRACT: The United States faces a crisis because of the high prevalence of chronic pain, concurrent opioid use disorder, and overdose deaths. Prescription opioids remain a primary driver of opioid-related deaths. Craving is a core symptom of addiction, yet the degree to which craving plays a role in prescription opioid use among patients with chronic pain is unknown. Understanding the degree to which craving should be considered in patients with chronic pain is critical for developing effective interventions for supporting patients through opioid tapering. The current work combines data collected from (1) 2152 veterans screened for eligibility at a pain specialty care clinic at the San Francisco VA Health Care System and (2) medical records obtained from the VA Corporate Data Warehouse. We found that prescription opioid craving among veterans with chronic pain was low, with 66.4% of the sample reporting no craving and 33.6% reporting craving. We also found that craving had a small association with morphine equivalent daily dose and pain severity but was more strongly associated with depression. Craving of prescription opioids among veterans with chronic pain is complex. Findings are discussed in relation to chronic pain symptoms, psychiatric comorbidities, and demographics.

Age-dependent brain morphometry in Major Depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a complex disorder that affects nearly 264 million people worldwide. Structural brain abnormalities in multiple neuroanatomical networks have been implicated in the etiology of MDD, but the degree to which MDD affects brain structure during early to late adulthood is unclear. METHODS: We examined morphometry of brain regions commonly implicated in MDD, including the amygdala, hippocampus, anterior cingulate gyrus, lateral orbitofrontal gyrus, subgenual cortex, and insular cortex subregions, from early to late adulthood. Harmonized measures for gray matter (GM) volume and cortical thickness of each region were estimated cross-sectionally for 305 healthy controls (CTLs) and 247 individuals with MDD (MDDs), collated from four research cohorts. We modeled the nonlinear associations of age with GM volume and cortical thickness using generalized additive modeling and tested for age-dependent group differences. RESULTS: Overall, all investigated regions exhibited smaller GM volume and thinner cortical measures with increasing age. Compared to age matched CTLs, MDDs had thicker cortices and greater GM volume from early adulthood until early middle age (average 35 years), but thinner cortices and smaller GM volume during and after middle age in the lateral orbital gyrus and all insular subregions. Deviations of the MDD and CTL models for both GM volume and cortical thickness in these regions started as early as age 18. CONCLUSIONS: The analyses revealed that brain morphometry differences between MDDs and CTLs are dependent on age and brain region. The significant age-by-group interactions in the lateral orbital frontal gyrus and insular subregions make these regions potential targets for future longitudinal studies of MDD.

Association of painful human immunodeficiency virus distal sensory polyneuropathy with aberrant expectation of pain relief: functional magnetic resonance imaging evidence.

Mechanisms underlying chronic neuropathic pain associated with HIV-associated distal sensory polyneuropathy are poorly understood, yet 40% of those with distal neuropathy (or 20% of all people with HIV) suffer from this debilitating condition. Central pain processing mechanisms are thought to contribute to the development of HIV neuropathic pain, yet studies investigating central mechanisms for HIV neuropathic pain are few. Considering the motivational nature of pain, we aimed to examine the degree to which expectation of pain onset and expectation of pain offset are altered in sixty-one male patients with HIV-related distal sensory polyneuropathy with (N = 30) and without (N = 31) chronic neuropathic pain. By contrasting painful (foot) and non-painful (hand) sites between those with and without neuropathic pain, we could identify unique neural structures that showed altered activation during expectation of pain offset or relief. Our results showed no evidence for peripheral mechanisms evidenced by lack of significant between group differences in thermo-sensation, subjective pain response or epidermal nerve fibre density. Likewise, we found no significant differences between groups in subjective or brain mechanisms underlying the expectation of pain onset. Conversely, we found significant interaction within right anterior insula during expectation of pain offset in our study in that individuals in the pain group compared to the no-pain group exhibited increased anterior insula activation on the painful compared to the non-painful site. Our findings are consistent with abnormal processing of expectation of pain offset or abnormal pain relief-related mechanisms potentially due to increased emotional distress regarding the experience of chronic endogenous pain.

The Resurrection of Interdisciplinary Pain Rehabilitation: Outcomes Across a Veterans Affairs Collaborative.

OBJECTIVE: Despite empirical support for interdisciplinary pain rehabilitation programs improving functioning and quality of life, access to this treatment approach has decreased dramatically over the last 20 years within the United States but has grown significantly in the Department of Veterans Affairs (VA). Between 2009 and 2019, VA pain rehabilitation programs accredited by the Commission on Accreditation of Rehabilitation Facilities increased 10-fold in the VA, expanding from two to 20. The aim of this collaborative observational evaluation was to examine patient outcomes across a subset of six programs at five sites. METHODS: Outcomes were assessed using agreed-upon measures of patient-reported pain intensity, pain interference across various domains, pain catastrophizing, and sleep. RESULTS: A total of 931 patients enrolled in the selected VA interdisciplinary pain programs, with 84.1% of participants completing the full course of treatment. Overall, all programs showed significant improvements from pretreatment to posttreatment in nearly all patient-reported outcomes. The effect sizes ranged from medium to large. Notably, the results demonstrate that positive outcomes were typical despite differences in structure and resources across programs. CONCLUSIONS: The adverse impacts of opioid use have highlighted the importance of chronic pain treatment approaches that emphasize team-based care focused on functional improvements. This study represents the first and largest analysis of outcomes across chronic pain rehabilitation programs and demonstrates the need for increased access to similar comprehensive approaches to pain management across the health care system. Further, it suggests that a variety of structures may be effective, encouraging flexibility in adopting this interdisciplinary approach.

Onset hyperalgesia and offset analgesia: Transient increases or decreases of noxious thermal stimulus intensity robustly modulate subsequent perceived pain intensity.

Reported pain intensity depends not only on stimulus intensity but also on previously experienced pain. A painfully hot temperature applied to the skin evokes a lower subjective pain intensity if immediately preceded by a higher temperature, a phenomenon called offset analgesia. Previous work indicated that prior pain experience can also increase subsequent perceived pain intensity. Therefore, we examined whether a given noxious stimulus is experienced as more intense when it is preceded by an increase from a lower temperature. Using healthy volunteer subjects, we observed a disproportionate increase in pain intensity at a given stimulus intensity when this intensity is preceded by a rise from a lower intensity. This disproportionate increase is similar in magnitude to that of offset analgesia. We call this effect onset hyperalgesia. Control stimuli, in which a noxious temperature is held constant, demonstrate that onset hyperalgesia is distinct from receptor or central sensitization. The absolute magnitudes of offset analgesia and onset hyperalgesia correlate with each other but not with the noxious stimulus temperature. Finally, the magnitude of both offset analgesia and onset hyperalgesia depends on preceding temperature changes. Overall, this study demonstrates that the perceptual effect of a noxious thermal stimulus is influenced in a bidirectional manner depending upon both the intensity and direction of change of the immediately preceding thermal stimulus.

Multimodal canonical correlation reveals converging neural circuitry across trauma-related disorders of affect and cognition.

Trauma-related disorders of affect and cognition (TRACs) are associated with a high degree of diagnostic comorbidity, which may suggest that these disorders share a set of underlying neural mechanisms. TRACs are characterized by aberrations in functional and structural circuits subserving verbal memory and affective anticipation. Yet, it remains unknown how the neural circuitry underlying these multiple mechanisms contribute to TRACs. Here, in a sample of 47 combat Veterans, we measured affective anticipation using functional magnetic resonance imaging (fMRI), verbal memory with fluorodeoxyglucose positron emission tomography (FDG-PET), and grey matter volume with structural magnetic resonance imaging (sMRI). Using a voxel-based multimodal canonical correlation analysis (mCCA), the set of neural measures were statistically integrated, or fused, with a set of TRAC symptom measures including mild traumatic brain injury (mTBI), posttraumatic stress, and depression severity. The first canonical correlation pair revealed neural convergence in clusters encompassing the middle frontal gyrus and supplemental motor area, regions implicated in top-down cognitive control and affect regulation. These results highlight the potential of leveraging multivariate neuroimaging analysis for linking neurobiological mechanisms associated with TRACs, paving the way for transdiagnostic biomarkers and targets for treatment.

Fear as a translational mechanism in the psychopathology of anorexia nervosa.

Anorexia nervosa (AN) is an often chronic and potentially lethal psychiatric disorder, for which the precise etiology remains elusive. While current treatment outcomes are modest at best, it is thought that the identification of translational mechanisms driving the psychopathology of AN will assist in the development and optimization of novel treatments. AN is a disorder characterized by fear and avoidance, hypervigilant scrutiny of one's body, and an unnatural fear of weight gain. Moreover, a suite of anxious traits and regimentation of behavior are atypically common well in advance of the onset of restrictive eating in those with AN. Here we consider the promise of shedding light on causal mechanisms of AN by interrogating the role of fear-related learning, deficits in discriminating safety cues, and extinction of acquired fear. We offer a translational rationale for this line of inquiry, and discuss the clinical implications of considering fear as a translational mechanism in the psychopathology of AN.

An exploratory examination of reappraisal success in depressed adolescents: Preliminary evidence of functional differences in cognitive control brain regions.

BACKGROUND: Most neuroimaging studies of adolescent depression employ tasks not designed to engage brain regions necessary for the cognitive control of emotion, which is central to many behavioral therapies for depression. Depressed adults demonstrate less effective activation of these regions and greater amygdala activation during cognitive reappraisal; we examined whether depressed adolescents show similar patterns of brain activation. METHODS: We collected functional magnetic resonance imaging (fMRI) data during cognitive reappraisal in 41 adolescents with major depressive disorder (MDD) and 34 matched controls (ages 13-17). We examined group differences in (1) activations associated with reappraisal and reappraisal success (i.e., negative affect reduction during reappraisal) using whole brain and amygdala region-of-interest analyses, and (2) functional connectivity of regions from the group-by-reappraisal success interaction. RESULTS: We found no significant group differences in whole brain or amygdala analyses during reappraisal. In the group-by-reappraisal success interaction, activations in the left dorsomedial prefrontal cortex (dmPFC) and left dorsolateral PFC (dlPFC) were associated with reappraisal success in healthy controls but not depressed adolescents. Depressed adolescents demonstrated reduced connectivity between the left dmPFC and the anterior insula/inferior frontal gyri bilaterally (AI/IFG) and between left dlPFC and left AI/IFG. LIMITATIONS: Our results should be considered exploratory given our less conservative statistical threshold in the group-by-reappraisal interaction. CONCLUSIONS: We find preliminary evidence that depressed adolescents engage cognitive control regions less efficiently than healthy controls, suggesting delayed maturation of regulatory prefrontal cortex regions; more research is needed to determine whether cognitive therapies improve functioning of these regions in depressed youth.

An Interdisciplinary Pain Rehabilitation Program for Veterans with Chronic Pain: Description and Initial Evaluation of Outcomes.

Objective: Chronic pain conditions are prominent among Veterans. To leverage the biopsychosocial model of pain and comprehensively serve Veterans with chronic pain, the San Francisco Veterans Affairs Healthcare System has implemented the interdisciplinary pain rehabilitation program (IPRP). This study aims to (1) understand initial changes in treatment outcomes following IPRP, (2) investigate relationships between psychological factors and pain outcomes, and (3) explore whether changes in psychological factors predict changes in pain outcomes. Methods: A retrospective study evaluated relationships between clinical pain outcomes (pain intensity, pain disability, and opioid use) and psychological factors (depressive symptoms, catastrophizing, and "acceptable" level of pain) and changes in these outcomes following treatment. Multiple regression analysis explored whether changes in psychological variables significantly predicted changes in pain disability. Results: Catastrophizing and depressive symptoms were positively related to pain disability, while "acceptable" level of pain was idiosyncratically related to pain intensity. Pain disability and psychological variables showed significant changes in their expected directions. Regression analysis indicated that only changes in depressive symptoms significantly predicted changes in pain disability. Conclusion: Our results are consistent with evidence-based clinical practice guidelines for the management of chronic pain in Veterans. Further investigation of interdisciplinary treatment programs in Veterans is warranted.

Anorexia nervosa, neuroimaging research, and the contextual salience of food cues: The food approach-avoidance conundrum.

Anorexia nervosa (AN) is characterized by an avoidance and marked apprehension around food intake, yet paradoxically, those with AN often display approach behaviors to food, engaging in food shopping or preparation activities which are described as rewarding. This approach-avoidance conundrum is of much importance as neuroimaging studies continue to probe mechanisms relating to core AN psychopathology. This Idea Worth Researching discusses the notion that neuroimaging studies relying on food cue presentation paradigms may be methodologically flawed without specifying the contextual salience of the food cues presented in paradigms. The appraisal of food cues may diverge as a function of one's intent-to-eat, and thus, neuroimaging studies not specifying the contextual salience of food cues (i.e., intent-to-eat or not) may confound two distinctly different processes.