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Abstract Background Reverse total shoulder arthroplasty (RTSA) is commonly performed to reduce pain and restore shoulder function in patients with severe shoulder conditions. While most patients experience significant pain relief and functional improvement following surgery, a subset of patients continue to report persistent pain even two years postoperatively. The aim of this study was to identify both modifiable and non-modifiable preoperative factors that contribute to the risk of persistent postsurgical pain after RTSA. By understanding these factors, clinicians can better anticipate which patients are at higher risk and develop tailored preoperative and postoperative pain management strategies to improve overall outcomes. Methods In this retrospective cohort study, 703 patients with complete data undergoing primary RTSA performed between 2011 and 2022 were analyzed. Persistent postsurgical pain was defined as a pain score ≥ 3 on a numeric rating scale. Multivariable regression models were used to identify patient-related and disease-related predictors of persistent postsurgical pain. Results The cohort comprised 445 women (63%) and 258 men (37%) with a mean age of 74 ± 8 years at the time of surgery. Persistent postsurgical pain was reported by 18% of patients. Preoperative pain scores averaged 6.0 ± 2.5 on the NRS scale, which decreased to 1.2 ± 1.8 postoperatively. Key predictors included higher preoperative pain levels (β = 0.10, p

Chronic pain syndromes affect over one-third of the US adult population and often lead to significant disability and a reduced quality of life. Despite their high prevalence, causal links between chronic pain syndromes and anatomic abnormalities are often not apparent. Most current chronic pain treatments provide modest, if any, relief. Thus, there is a pressing need to understand the causal mechanisms implicated in chronic pain as a means to develop more targeted interventions for improvement in clinical outcomes and reduction in morbidity and financial burden. In the present manuscript, we summarize the current literature on treatment for chronic pain, and hypothesize that non-specific chronic back pain (without a clear organic etiology, such as tumors, infections or fractures) is of psychophysiologic origin. Based on this hypothesis, we developed Psychophysiologic Symptom Relief Therapy (PSRT), a novel pain reduction intervention for understanding and treating chronic pain. In this manuscript, we provide the rationale for PSRT, which we have tested in a pilot trial with a subsequent larger randomized trial underway. In the proposed trial, we will evaluate whether non-specific chronic back pain can be treated by addressing the underlying stressors and psychological underpinnings without specific physical interventions.

Abstract Background Mastectomies are commonly performed and strongly associated with chronic postsurgical pain (CPSP), more specifically termed postmastectomy pain syndrome (PMPS), with 25–60% of patients reporting pain 3 months after surgery. PMPS interferes with function, recovery, and compliance with adjuvant therapy. Importantly, it is associated with chronic opioid use, as a recent study showed that 1 in 10 patients continue to use opioids at least 3 months after curative surgery. The majority of PMPS patients are women, and, over the past 10 years, women have outpaced men in the rate of growth in opioid dependence. Standard perioperative multimodal analgesia is only modestly effective in prevention of CPSP. Thus, interventions to reduce CPSP and PMPS are urgently needed. Ketamine is well known to improve pain and reduce opioid use in the acute postoperative period. Additionally, ketamine has been shown to control mood in studies of anxiety and depression. By targeting acute pain and improving mood in the perioperative period, ketamine may be able to prevent the development of CPSP. Methods Ketamine analgesia for long-lasting pain relief after surgery (KALPAS) is a phase 3, multicenter, randomized, placebo-controlled, double-blind trial to study the effectiveness of ketamine in reducing PMPS. The study compares continuous perioperative ketamine infusion vs single-dose ketamine in the postanesthesia care unit vs placebo for reducing PMPS. Participants are followed for 1 year after surgery. The primary outcome is pain at the surgical site at 3 months after the index surgery as assessed with the Brief Pain Inventory-short form pain severity subscale. Discussion This project is part of the NIH Helping to End Addiction Long-term (HEAL) Initiative, a nationwide effort to address the opioid public health crisis. This study can substantially impact perioperative pain management and can contribute significantly to combatting the opioid epidemic. Trial registration ClinicalTrials.gov NCT05037123. Registered on September 8, 2021.

Abstract. Introduction:. Patients with fibromyalgia show impaired cognitive performance compared with healthy, pain-free controls. Sleep disturbance, anxiety, and depression are highly prevalent among patients with fibromyalgia, and each is associated with impaired cognitive performance. Yet, limited work has explored whether psychosocial factors contribute to group differences in cognitive performance. Objectives:. This secondary data analysis investigated differences in cognitive performance between patients with fibromyalgia and healthy controls, and whether psychosocial factors accounted for these differences. Methods:. Adults with fibromyalgia (N = 24) and healthy, pain-free controls (N = 26) completed 2 cognitive tasks and the Patient-Reported Outcomes Measurement Information System sleep disturbance, anxiety, and depression short forms. Independent samples t tests were used to test for differences in cognitive performance between patients with fibromyalgia and healthy controls. Pearson correlations were conducted to examine associations between psychosocial factors and cognitive performance. Psychosocial factors significantly related to cognitive performance were explored as potential mediators of group differences in cognitive performance. Results:. Patients with fibromyalgia demonstrated poorer accuracy for divided attention compared with healthy controls, and sleep disturbance mediated this group difference. On the attentional switching task, healthy controls showed a greater switch-cost for accuracy compared with patients with fibromyalgia, but there was no group difference in reaction time. Anxiety and depression were not related to cognitive performance. Conclusion:. We found that patients with fibromyalgia reported greater sleep disturbance and, in turn, had poorer accuracy on the divided attention task. Sleep disturbance is modifiable with behavioral interventions, such as cognitive behavioral therapy, and may be a target for improving sleep quality and cognitive performance among patients with fibromyalgia.

IntroductionPain catastrophizing, a measure of an individual's negative emotional and cognitive appraisals of pain, has been included as a key treatment target in many psychological interventions for pain. However, the neural correlates of pain catastrophizing have been understudied. Prior neuroimaging evidence suggests that adults with pain show altered reward processing throughout the mesocorticolimbic reward circuitry.MethodsIn this study, we tested the association between Pain Catastrophizing Scale (PCS) scores and neural activation to the Monetary Incentive Delay (MID) reward neuroimaging task in 94 adults reporting a range of pain, insomnia, and mood symptoms.ResultsResults indicated that PCS score but not pain intensity was significantly associated with blunted activation in the caudate and putamen in response to feedback of successful vs. unsuccessful trials on the MID task. Mediation analyses indicated that PCS score fully mediated the relationship between depression symptoms and reward activation.DiscussionThese findings provide evidence that pain catastrophizing is independently associated with altered striatal function apart from depression symptoms and pain intensity. Thus, in individuals experiencing pain and/or co- morbid conditions, reward dysfunction is directly related to pain catastrophizing.

Abstract 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.

Objective The aim of this study was to assess the feasibility and potential effectiveness of an 8-week virtual EMG biofeedback intervention for patients with CLBP. Methods Patients with CLBP completed validated baseline and post-intervention assessments of pain intensity and interference (Brief Pain Inventory), back pain-related disability (Oswestry Disability Index), anxiety and depression (Hospital Anxiety and Depression Scale). Participants underwent a series of Quantitative Sensory Testing (QST) procedures assessing responses to mechanical stimuli during two separate visits (baseline and post-intervention). In addition, we assessed, using surface EMG, the muscle tension in the trapezius, latissimus, and low back muscles at each session. Patients were randomized into the EMG biofeedback intervention or usual care group. Factorial analysis of variance including the interaction between treatment group and time was used to analyze the changes in pain intensity (primary outcome), pain interference, disability (secondary outcomes), anxiety, and depression (secondary outcomes). Results Compared to the treatment as usual comparison group, patients in the EMG biofeedback group reported lower pain intensity after completing the intervention (mean group difference 0.9, 95% CI −1.07, −0.32; p ≤0.01). Compared to baseline, participants in the EMG biofeedback group demonstrated statistically significant reductions in pain interference (mean difference 1.3, 95% CI 0.42, 2.1; p ≤0.01), disability (mean difference 4.32, 95% CI 1.2, 7.3; p ≤0.01), and significant increases in low back pain thresholds (mean difference 0.5, 95% CI −0.87, −0.05; p ≤0.01), assessed by QST. However, no significant group by time effects were observed for secondary outcomes: pain interference, disability, and low back pain thresholds. In addition, significant changes were observed in muscle tension for the trapezius, latissimus, and low back muscles in the EMG biofeedback group ( p

Abstract Patient–clinician concordance in behavior and brain activity has been proposed as a potential key mediator of mutual empathy and clinical rapport in the therapeutic encounter. However, the specific elements of patient–clinician communication that may support brain-to-brain concordance and therapeutic alliance are unknown. Here, we investigated how pain-related, directional facial communication between patients and clinicians is associated with brain-to-brain concordance. Patient–clinician dyads interacted in a pain-treatment context, during synchronous assessment of brain activity (fMRI hyperscanning) and online video transfer, enabling face-to-face social interaction. In-scanner videos were used for automated individual facial action unit (AU) time-series extraction. First, an interpretable machine-learning classifier of patients’ facial expressions, from an independent fMRI experiment, significantly distinguished moderately painful leg pressure from innocuous pressure stimuli. Next, we estimated neural-network causality of patient-to-clinician directional information flow of facial expressions during clinician-initiated treatment of patients’ evoked pain. We identified a leader–follower relationship in which patients predominantly led the facial communication while clinicians responded to patients’ expressions. Finally, analyses of dynamic brain-to-brain concordance showed that patients’ mid/posterior insular concordance with the clinicians’ anterior insula cortex, a region identified in previously published data from this study1, was associated with therapeutic alliance, and self-reported and objective (patient-to-clinician-directed causal influence) markers of negative-affect expressivity. These results suggest a role of patient-clinician concordance of the insula, a social-mirroring and salience-processing brain node, in mediating directional dynamics of pain-directed facial communication during therapeutic encounters.

Abstract Objective Chronic pain can have detrimental effects on quality of life and a profound impact on one’s identity. The Pictorial Representation of Illness- and Self-Measure (PRISM), is a visual tool designed to measure the self-illness separation (SIS) that represents the degree of schema-enmeshment (i.e., the degree to which the self-schema and the illness-schema come to overlap). Our aim was to investigate the relationship between schema-enmeshment and pain-related outcomes in patients with fibromyalgia. Methods In this cross-sectional study, 114 patients with fibromyalgia completed self-report assessments of pain catastrophizing, pain severity and interference, impact of symptoms, anxiety, and depression. SIS was assessed using an iPad version of PRISM. Mediation analyses evaluated the mediating role of schema-enmeshment on the association between pain catastrophizing and fibromyalgia impact. Results A higher degree of schema-enmeshment was associated with greater pain catastrophizing, pain severity and interference, impact of symptoms, and depression. Moreover, a mediation analysis revealed that schema-enmeshment significantly mediated the association between pain catastrophizing and fibromyalgia impact (p

Thalamocortical dysrhythmia is a key pathology of chronic pain. Here, the authors propose an analytical pipeline to study dynamic fMRI brain networks and demonstrate that chronic low back pain pathophysiology and clinical pain intensity are associated with distinct thalamocortical network dynamics.

Optimization of pain assessment and treatment is an active area of research in healthcare. The purpose of this research is to create an objective pain intensity estimation system based on multimodal sensing signals through experimental studies. Twenty eight healthy subjects were recruited at Northeastern University. Nine physiological modalities were utilized in this research, namely facial expressions (FE), electroencephalography (EEG), eye movement (EM), skin conductance (SC), and blood volume pulse (BVP), electromyography (EMG), respiration rate (RR), skin temperature (ST), blood pressure (BP). Statistical analysis and machine learning algorithms were deployed to analyze the physiological data. FE, EEG, SC, BVP, and BP proved to be able to detect different pain states from healthy subjects. Multi-modalities proved to be promising in detecting different levels of painful states. A decision-level multi-modal fusion also proved to be efficient and accurate in classifying painful states.

Introduction:. Both positive (burning, stabbing, and allodynia) and negative (numbness) neuropathic symptoms may arise after surgery but likely contribute differently to patients' postoperative pain experience. Numbness has been identified as divergent from positive neuropathic symptoms and therefore excluded from some neuropathic assessment tools (Neuropathic Pain Scale for PostSurgical patients [NeuPPS]). Objectives:. In this prospective longitudinal study of patients undergoing breast surgery, we aimed to delineate the time course of numbness and its coincidence with NeuPPS and to contrast the association of surgical, psychosocial, and psychophysical predictors with the development of negative vs positive neuropathic symptoms. Methods:. Patients reported surgical area sensory disturbances at 2 weeks and 3, 6, and 12 months postoperatively. Association of baseline demographic, surgical, psychosocial, and psychophysical factors with NeuPPS and numbness across time was investigated using generalized estimating equation linear and logistic regression. Results:. Numbness was consistently reported by 65% of patients; positive neuropathic symptoms were less common, often decreasing over time. Neuropathic Pain scale for PostSurgical patients and numbness co-occurred in half of patients and were both associated with greater clinical pain severity and impact, younger age, axillary surgery, and psychosocial factors. More extensive surgery and chemotherapy were only associated with numbness. Conversely, other chronic pain, lower physical activity, perioperative opioid use, negative affect, and lower baseline pressure pain threshold and tolerance were only associated with NeuPPS. Patients reporting numbness alone did not endorse substantial clinical pain. Conclusions:. Differentiation of predictors, prevalence, and time course of numbness vs NeuPPS in breast surgical patients revealed important distinctions, suggesting that their independent assessment is worthwhile in future studies of postsurgical pain.

Abstract Background Knee osteoarthritis (OA) is among the most common and disabling persistent pain conditions, with increasing prevalence in the developed world, and affects women to a greater degree than men. In the USA, the growth of knee OA has been paralleled by an increase in rates of total knee arthroplasty (TKA), a surgical treatment option for late-stage knee OA. While TKA outcomes are generally good, postoperative trajectories of pain vary widely, with some patients reporting a complete absence of pain, but with a significant minority reporting worsening pain. Biopsychosocial factors, including anxiety and depression, are known to contribute importantly to the experience of joint pain, with women reporting a higher degree of negative affective symptoms. Methods This study investigated sex differences in TKA outcomes in age-matched groups of men and women at two academic medical centers. Pain and physical function were assessed in 100 patients (50 men and 50 women) during the perioperative period (preoperative visit—6 weeks postsurgical). The association of preoperative negative affect (anxiety and depression scores) to postoperative pain and function was evaluated, with specific attention to sex differences in this relationship. Results Overall, women reported more baseline pain-related physical dysfunction (although not higher baseline pain scores), as well as higher acute postoperative pain scores during the 2 weeks following TKA than their male counterparts. By 6 weeks postoperatively, sex differences in reported pain were no longer evident. Interestingly, although women reported higher preoperative levels of emotional distress than men, preoperative anxiety and depression scores were better predictors of severe postoperative pain among men than women, throughout the postoperative test period. Conclusions This study underlines the importance of considering sex and psychosocial factors, as well as their interaction, in understanding postsurgical pain trajectories.

Abstract. There is tremendous interpatient variability in the response to analgesic therapy (even for efficacious treatments), which can be the source of great frustration in clinical practice. This has led to calls for “precision medicine” or personalized pain therapeutics (ie, empirically based algorithms that determine the optimal treatments, or treatment combinations, for individual patients) that would presumably improve both the clinical care of patients with pain and the success rates for putative analgesic drugs in phase 2 and 3 clinical trials. However, before implementing this approach, the characteristics of individual patients or subgroups of patients that increase or decrease the response to a specific treatment need to be identified. The challenge is to identify the measurable phenotypic characteristics of patients that are most predictive of individual variation in analgesic treatment outcomes, and the measurement tools that are best suited to evaluate these characteristics. In this article, we present evidence on the most promising of these phenotypic characteristics for use in future research, including psychosocial factors, symptom characteristics, sleep patterns, responses to noxious stimulation, endogenous pain-modulatory processes, and response to pharmacologic challenge. We provide evidence-based recommendations for core phenotyping domains and recommend measures of each domain.

Chronic low back pain (cLBP) is a prevalent disorder. A growing body of evidence linking the pathology of the reward network to chronic pain suggests that pain sensitization may contribute to cLBP chronification via disruptions of mesocortical and mesolimbic circuits in the reward system. Resting-state (RS) functional magnetic resonance imaging (fMRI) data was acquired from 90 patients with cLBP and 74 matched pain-free controls (HCs) at baseline and after a manipulation for back pain intensification. The ventral tegmental area (VTA) was chosen as a seed region to perform RS functional connectivity (FC) analysis. Baseline rsFC of both the mesocortical (between the VTA and bilateral rostral anterior cingulate cortex (rACC)/and medial prefrontal cortex (mPFC)) and mesolimbic (between the VTA and bilateral hippocampus/parahippocampus) pathways was reduced in patients with cLBP (vs. HCs). In addition, patients exhibiting higher back pain intensity (compared to the relatively lower back pain intensity condition) also showed increases in both mesocortical and mesolimbic connectivity, implicating these pathways in pain downregulation in cLBP. Mediation analysis further isolated the mesolimbic (VTA-hippocampus/parahippocampus) dysconnectivity as a neural mechanism mediating the association between mechanical pain sensitivity (indexed by P40 pressure) and cLBP severity. In sum, the current study demonstrates deficient mesocorticolimbic connectivity in cLBP, with mesolimbic dysconnectivity potentially mediating the contribution of pain sensitization to pain chronification. These reward network dysfunctions and purportedly, dopaminergic dysregulations, may help us to identify key brain targets of neuromodulation in the treatment of cLBP.

Abstract. Introduction:. Fibromyalgia (FM) is a condition marked by widespread chronic pain and an array of somatic and psychological symptoms. The primary objective of this study was to explore daily associations between physical activity and pain intensity among a sample of women with FM and the potential moderation of this association by pain catastrophizing. Methods:. Women with FM (N = 107) completed questionnaires assessing pain, FM symptoms, and psychological measures and were then asked to report their levels of daily pain catastrophizing, physical activity, and pain intensity once per day for a period of 1 week using daily electronic diary-based tracking. In addition, objective measures of physical activity were collected using an activity tracker (Fitbit Flex), which measured step counts. Daily self-report physical activity was used as the independent variable and pain intensity (Brief Pain Inventory) was the outcome, whereas daily pain catastrophizing was tested in the model as the potential moderator. Results:. Moderation analyses demonstrated associations between physical activity and pain intensity, which were moderated by patient's level of catastrophizing (B = 0.003, SE = 0.001, P < 0.05), with patients scoring higher in daily catastrophizing showing a relatively stronger link between higher day-to-day physical activity and increased daily FM pain. Significant associations were observed between pain catastrophizing, pain intensity, and Fitbit Flex step count (P < 0.05). Conclusions:. Our findings suggest that increases in daily physical activity is associated with more self-reported pain intensity in women with FM pain, particularly among those with higher levels of pain catastrophizing.

Prior studies have shown that patients suffering from chronic Low Back Pain (cLBP) have impaired somatosensory processing including reduced tactile acuity, i.e. reduced ability to resolve fine spatial details with the perception of touch. The central mechanism(s) underlying reduced tactile acuity are unknown but may include changes in specific brain circuitries (e.g. neuroplasticity in the primary somatosensory cortex, S1). Furthermore, little is known about the linkage between changes in tactile acuity and the amelioration of cLBP by somatically-directed therapeutic interventions, such as acupuncture. In this longitudinal neuroimaging study, we evaluated healthy control adults (HC, N ​= ​50) and a large sample of cLBP patients (N ​= ​102) with structural brain imaging (T1-weighted MRI for Voxel-Based Morphometry, VBM; Diffusion Tensor Imaging, DTI) and tactile acuity testing using two-point discrimination threshold (2PDT) over the lower back (site of pain) and finger (control) locations. Patients were evaluated at baseline and following a 4-week course of acupuncture, with patients randomized to either verum acupuncture, two different forms of sham acupuncture (designed with or without somatosensory afference), or no-intervention usual care control. At baseline, cLBP patients demonstrated reduced acuity (greater 2PDT, P ​= ​0.01) over the low back, but not finger (P ​= ​0.29) locations compared to HC, suggesting that chronic pain affects tactile acuity specifically at body regions encoding the experience of clinical pain. At baseline, Gray Matter Volume (GMV) was elevated and Fractional Anisotropy (FA) was reduced, respectively, in the S1-back region of cLBP patients compared to controls (P ​

Background: Chronic pain and mood disorders share common neuroanatomical substrates involving disruption of the reward system. Although increase in negative affect (NA) and decrease in positive affect (PA) are well-known factors complicating the clinical presentation of chronic pain patients, our understanding of the mechanisms underlying the interaction between pain and PA/NA remains limited. Here, we used a validated task probing behavioral and neural responses to monetary rewards and losses in conjunction with functional magnetic resonance imaging (fMRI) to test the hypothesis that dysfunction of the striatum, a key mesolimbic structure involved in the encoding of motivational salience, relates to mood alterations comorbid with chronic pain. Methods: Twenty-eight chronic musculoskeletal pain patients (chronic low back pain, n=15; fibromyalgia, n=13) and 18 healthy controls underwent fMRI while performing the Monetary Incentive Delay (MID) task. Behavioral and neural responses were compared across groups and correlated against measures of depression (Beck Depression Inventory) and hedonic capacity (Snaith-Hamilton Pleasure Scale). Results: Compared to controls, patients demonstrated higher anhedonia and depression scores, and a dampening of striatal activation and incentive-related behavioral facilitation (reduction in reaction times) during reward and loss trials of the MID task (ps ​

Background: Fibromyalgia (FM) is characterized by widespread pain, sleep disturbance, negative affect, and stress and is notably difficult to treat. Individuals with FM have lower physical activity and endorse fears that exercise may worsen pain. Gentle daily yoga practice may allow a gradual increase in activity and positively impact many of these FM symptoms. This qualitative study investigated the impact of participation in a pilot trial of group and daily individual home yoga intervention on women with FM. Materials and Methods: Fifteen individuals participated in telephone interviews after participating in the yoga intervention, which included semi-structured questions to elicit insights and impressions of their experience. Responses were systematically coded and themes identified. Results: Five themes were identified: (1) physical/body perceptual changes, (2) practices affecting pain, (3) emotional changes, (4) practice motivators and barriers, and (5) group effect. Participants not only reported reductions in FM symptoms, including pain and stress, but also a positive impact on mood, sleep, and self-confidence. Conclusions: Participants enumerated both physical and psychological impact of starting yoga practice. Specific helpful poses and practices and important barriers were identified. Group practice and social connection with others with other FM patients was an important benefit to participants.

Abstract. Introduction:. Chronic pain patients frequently report having sleep disturbances and many tend to stay up during the night and then sleep into the day. Objectives:. This study was designed to compare a heterogeneous group of persons with chronic pain who reported typically going to bed between the hours of 9 pm and midnight with those who go to bed at other hours of the day and night. Methods:. Two hundred seventy-nine participants were divided between those who reported going to bed between the hours of 9 pm and midnight (N = 205) and those who reported having atypical bedtimes (N = 74) based on pre–post questionnaire data and average pain assessments from a smartphone pain application (app). Results:. Those individuals in the atypical bedtime group reported waking up more frequently and getting fewer hours sleep (P < 0.05). These individuals also reported significantly higher pain scores, activity interference, and taking more prescription opioid medication compared with those who had typical bedtimes (P < 0.05). Based on average 3-month daily assessments, those subjects with an atypical bedtime consistently reported more sleep disturbances, pain, activity interference, negative mood, and general worsening conditions over time, and elevated pain catastrophizing, pain-related disability, emotional distress scores, and more prescription medication for pain at 3-month follow-up (P < 0.01). Conclusion:. These results support the importance of providers asking patients with pain about what time they typically go to bed at night to gain a greater understanding of their lifestyle habits. Future studies are needed to further determine the importance of maintaining a typical bedtime among patients with chronic pain.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Chronic low back pain (cLBP) is associated with widespread functional and structural changes in the brain. This study aims to investigate the resting state functional connectivity (rsFC) changes of visual networks in cLBP patients and the feasibility of distinguishing cLBP patients from healthy controls using machine learning methods. cLBP (n = 90) and control individuals (n = 74) were enrolled and underwent resting-state BOLD fMRI scans. Primary, dorsal, and ventral visual networks derived from independent component analysis were used as regions of interest to compare resting state functional connectivity changes between the cLBP patients and healthy controls. We then applied a support vector machine classifier to distinguish the cLBP patients and control individuals. These results were further verified in a new cohort of subjects. We found that the functional connectivity between the primary visual network and the somatosensory/motor areas were significantly enhanced in cLBP patients. The rsFC between the primary visual network and S1 was negatively associated with duration of cLBP. In addition, we found that the rsFC of the visual network could achieve a classification accuracy of 79.3% in distinguishing cLBP patients from HCs, and these results were further validated in an independent cohort of subjects (accuracy = 66.7%). Our results demonstrate significant changes in the rsFC of the visual networks in cLBP patients. We speculate these alterations may represent an adaptation/self-adjustment mechanism and cross-model interaction between the visual, somatosensory, motor, attention, and salient networks in response to cLBP. Elucidating the role of the visual networks in cLBP may shed light on the pathophysiology and development of the disorder. Keywords: Chronic low back pain, Vision system, fMRI, Cross-modal perception, Attention, Resting state functional connectivity

Despite the high prevalence and socioeconomic impact of chronic low back pain (cLBP), treatments for cLBP are often unsatisfactory, and effectiveness varies widely across patients. Recent neuroimaging studies have demonstrated abnormal resting-state functional connectivity (rsFC) of the default mode, salience, central executive, and sensorimotor networks in chronic pain patients, but their role as predictors of treatment responsiveness has not yet been explored. In this study, we used machine learning approaches to test if pre-treatment rsFC can predict responses to both real and sham acupuncture treatments in cLBP patients. Fifty cLBP patients participated in 4 weeks of either real (N = 24, age = 39.0 ± 12.6, 16 females) or sham acupuncture (N = 26, age = 40.0 ± 13.7, 15 females) treatment in a single-blinded trial, and a resting-state fMRI scan prior to treatment was used in data analysis. Both real and sham acupuncture can produce significant pain reduction, with those receiving real treatment experiencing greater pain relief than those receiving sham treatment. We found that pre-treatment rsFC could predict symptom changes with up to 34% and 29% variances for real and sham treatment, respectively, and the rsFC characteristics that were significantly predictive for real and sham treatment differed. These results suggest a potential way to predict treatment responses and may facilitate the development of treatment plans that optimize time, cost, and available resources. Keywords: Chronic low back pain, Acupuncture, Resting-state functional connectivity, Machine learning analysis, Treatment responses

The objective of this study was to examine the association between facets of trait mindfulness, pain catastrophizing, and pain severity in a sample of patients with fibromyalgia. Patients with fibromyalgia completed validated baseline and diary assessments of clinical pain, mindfulness, and pain catastrophizing. Multilevel modeling analyses indicated that the daily association between catastrophizing and pain intensity was moderated by certain mindfulness facets. Our findings suggest that various aspects of mindfulness may interact differently with pain and catastrophizing, which may have implications for the design and testing of interventions targeting mindfulness and catastrophizing in fibromyalgia patients.

Abstract. Background:. Epidemiological studies in patients with neuropathic pain demonstrate a strong association with psychiatric conditions such as anxiety; however, the precipitating pathology between these symptoms remains unclear. To investigate this, we studied the effects of lifelong stress on levels of neuropathic pain–like behavior and conversely, the effects of chronic neuropathic injury on anxiety-like status in male and female mice. In addition, we assayed this link in painful and painless diabetic peripheral neuropathy patients. Methods:. Male and female mice were subject to ongoing life-stress or control living conditions. Baseline sensitivity and anxiety tests were measured followed by spared nerve injury (SNI) to the sciatic nerve. Subsequent sensory testing occurred until 3 weeks after SNI followed by anxiety tests between 4 and 6 weeks after SNI. Results:. Levels of tactile or cold allodynia did not differ between adult mice subject to lifelong chronic stress, relative to nonstressed controls, for at least 3 weeks after SNI. By contrast, longer-term neuropathic mice of both sexes displayed pronounced anxiety-like behavior, regardless of exposure to stress. If sex differences were present, females usually exhibited more pronounced anxiety-like behavior. These ongoing anxiety behaviors were corroborated with plasma corticosterone levels in distinct animal groups. In addition, data from patients with painful and nonpainful diabetic neuropathy showed a clear relationship between ongoing pain and anxiety, with females generally more affected than males. Discussion:. Taken together, these data demonstrate a strong link between chronic neuropathic pain and chronic anxiety, with the driver of this comorbidity being neuropathic pain as opposed to on-going stress.

Altered brain morphometry has been widely acknowledged in chronic pain, and recent studies have implicated altered network dynamics, as opposed to properties of individual brain regions, in supporting persistent pain. Structural covariance analysis determines the inter-regional association in morphological metrics, such as gray matter volume, and such structural associations may be altered in chronic pain. In this study, voxel-based morphometry structural covariance networks were compared between fibromyalgia patients (N = 42) and age- and sex-matched pain-free adults (N = 63). We investigated network topology using spectral partitioning, which can delineate local network submodules with consistent structural covariance. We also explored white matter connectivity between regions comprising these submodules and evaluated the association between probabilistic white matter tractography and pain-relevant clinical metrics. Our structural covariance network analysis noted more connections within the cerebellum for fibromyalgia patients, and more connections in the frontal lobe for healthy controls. For fibromyalgia patients, spectral partitioning identified a distinct submodule with cerebellar connections to medial prefrontal and temporal and right inferior parietal lobes, whose gray matter volume was associated with the severity of depression in these patients. Volume for a submodule encompassing lateral orbitofrontal, inferior frontal, postcentral, lateral temporal, and insular cortices was correlated with evoked pain sensitivity. Additionally, the number of white matter fibers between specific submodule regions was also associated with measures of evoked pain sensitivity and clinical pain interference. Hence, altered gray and white matter morphometry in cerebellar and frontal cortical regions may contribute to, or result from, pain-relevant dysfunction in chronic pain patients.

Abstract. Background:. There is increasing concern among primary care practitioners about the use of opioids for chronic pain, including their adverse effects, but little attention has been given to how reports of side effects from prescription medication can contribute to outcomes among patients with chronic pain. The aim of this study was to investigate the impact of frequently reported side effects on mood, disability, and opioid misuse in patients with chronic pain prescribed opioids within primary care. Methods:. Two hundred (N = 200) patients with chronic pain taking opioids for pain were recruited into the study. All patients completed baseline measures and a monthly side effects checklist once a month for 6 months. Patients were divided evenly based on a median split of the number of endorsed side effects over 6 months. The subjects repeated the baseline measures at the end of the study period. Results:. Over time, reports of medication side effects tended to decrease, but differences in frequency of reported side effects from baseline to follow-up (6-month time) were not significant, and the order of the frequency of the reported side effects remained similar. Patients who reported significant medication-related adverse effects reported significantly greater activity interference, negative affect, and catastrophizing compared with those with fewer side effects (P < 0.01). In addition, those patients with pain who reported more side effects showed significantly higher scores on opioid misuse risk (P < 0.001). Discussion:. This study demonstrates the important role of monitoring medication-related side effects among patients with chronic pain who are prescribed opioid medication for pain within primary care.