sEMG Biofeedback for Episodic Migraines: A Pilot Randomized Clinical Trial.

The aim of this study was to assess the feasibility and potential effectiveness of a 6-week virtual sEMG biofeedback intervention for patients with episodic migraines. Patients with episodic migraines were randomized to treatment with a novel surface EMG (sEMG) at-home biofeedback device or a treatment as usual control group; they completed validated baseline and post-intervention assessments of migraine related disability (migraine-specific quality of life, anxiety and depression). Participants also underwent a series of Quantitative Sensory Testing (QST) procedures referring to several different tests that quantitatively assess responses to mechanical stimuli during two separate visits (baseline and post intervention). No adverse events were reported during the study. Compared to the treatment as usual comparison group, patients in the sEMG biofeedback group reported lower migraine disability (p < 0.05). Compared to baseline, participants in the sEMG biofeedback group demonstrated statistically significant reductions in anxiety (p < 0.01), and significant increases in quality of life (p < 0.001), and significant decreases in temporal summation (p < 0.05) assessed by QST. No significant changes were observed in any of the outcomes in the control comparison group (p > 0.05). No significant changes were observed in migraine frequency in either of the two groups (p > 0.05). In addition, mediation analyses revealed that changes in migraine related quality of life mediated group effects on changes in migraine disability. Virtual sEMG biofeedback shows promise as a potential therapy for reducing disability, anxiety and depression and improving quality of life in individuals with episodic migraines. These results demonstrate the feasibility of a digital intervention for migraines and set the basis for conducting a future, larger scale randomized controlled trial to confirm these preliminary findings.

A Randomized Controlled Neuroimaging Trial of Cognitive Behavioral Therapy for Fibromyalgia Pain.

OBJECTIVE: Fibromyalgia (FM) is characterized by pervasive pain-related symptomatology and high levels of negative affect. Mind-body treatments such as cognitive behavioral therapy (CBT) appear to foster improvement in FM via reductions in pain-related catastrophizing, a set of negative, pain-amplifying cognitive and emotional processes. However, the neural underpinnings of CBT's catastrophizing-reducing effects remain uncertain. This randomized controlled mechanistic trial was designed to assess CBT's effects on pain catastrophizing and its underlying brain circuitry. METHODS: Of 114 enrolled participants, 98 underwent a baseline neuroimaging assessment and were randomized to 8 weeks of individual CBT or a matched FM education control (EDU) condition. RESULTS: Compared with EDU, CBT produced larger decreases in pain catastrophizing post treatment (P < 0.05) and larger reductions in pain interference and symptom impact. Decreases in pain catastrophizing played a significant role in mediating those functional improvements in the CBT group. At baseline, brain functional connectivity between the ventral posterior cingulate cortex (vPCC), a key node of the default mode network (DMN), and somatomotor and salience network regions was increased during catastrophizing thoughts. Following CBT, vPCC connectivity to somatomotor and salience network areas was reduced. CONCLUSION: Our results suggest clinically important and CBT-specific associations between somatosensory/motor- and salience-processing brain regions and the DMN in chronic pain. These patterns of connectivity may contribute to individual differences (and treatment-related changes) in somatic self-awareness. CBT appears to provide clinical benefits at least partially by reducing pain-related catastrophizing and producing adaptive alterations in DMN functional connectivity.

Mindfulness-based Interventions for Chronic Low Back Pain: A Systematic Review and Meta-analysis.

OBJECTIVE: This systematic review aimed to compile existing evidence examining the effects of mindfulness-based interventions (MBIs) for chronic low back pain (CLBP). CLBP leads to millions of disabled individuals in the United States each year. Current pharmacologic treatments are only modestly effective and may present long-term safety issues. MBIs, which have an excellent safety profile, have been shown in prior studies to be effective in treating CLBP yet remained underutilized. DESIGN: Ovid/Medline, PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs), pilot RCTs, and single-arm studies that explored the effectiveness of MBIs in CLBP. METHODS: Separate searches were conducted to identify trials that evaluated MBIs in reducing pain intensity in individuals with CLBP. A meta-analysis was then performed using R v3.2.2, Metafor package v 1.9-7. RESULTS: Eighteen studies used validated patient-reported pain outcome measures and were therefore included in the meta-analysis. The MBIs included mindfulness meditation, mindfulness-based stress reduction, mindfulness-based cognitive therapy, mindfulness-oriented recovery enhancement, acceptance and commitment therapy, dialectical behavioral therapy, meditation-cognitive behavioral therapy, mindfulness-based care for chronic pain, self-compassion course, and loving-kindness course. Pain intensity scores were reported using a numerical rating scale (0 to 10) or an equivalent scale. The meta-analysis revealed that MBIs have a beneficial effect on pain intensity with a large-sized effect in adults with CLBP. CONCLUSIONS: MBIs seem to be beneficial in reducing pain intensity. Although these results were informative, findings should be carefully interpreted due to the limited data the high variability in study methodologies, small sample sizes, inclusion of studies with high risk of bias, and reliance on pre-post treatment differences with no attention to maintenance of effects. More large-scale RCTs are needed to provide reliable effect size estimates for MBIs in persons with CLBP.

Acceptance-Commitment Therapy for Women with Episodic Migraine: A Pilot Randomized Trial.

Objective: The aim of this study was to conduct a pilot, randomized controlled trial (RCT) of acceptance-commitment therapy (ACT) among women with episodic migraine, aged 18-65 years, and living in the United States. Background: Biobehavioral treatments have recently been proposed as possible preventive therapies for migraine management. ACT is a third wave biobehavioral therapy focused on acceptance and development of psychological flexibility and is evidence based for use in other chronic pain conditions. However, its use for reducing migraine frequency and disability has been understudied to date. Methods: The authors performed a pilot RCT evaluating ACT versus enhanced usual care (EUC) among adult women with episodic migraine. ACT consisted of eight virtual weekly sessions (for 8 weeks). Primary aims evaluated feasibility, retention, and protocol adherence. Secondary clinical outcomes included changes in migraine days and Migraine Disability Assessment (MIDAS). Results: We were able to successfully recruit 54 women in 15 months, which surpassed our recruitment goal. However, the completion rates of migraine logs and questionnaires at both outcome assessments were lower than anticipated. Among the 17 individuals randomized to EUC, 12 (71%) completed migraine logs and 12 (71%) completed questionnaires at the end of the intervention. In the postintervention follow-up, 11 (65%) individuals completed logs and 11 (65%) completed questionnaires. We observed slightly larger decreases in migraine days for those assigned to ACT from baseline to the end of the intervention, but these differences did not persist during postintervention follow-up. Both groups reported similar decreases in MIDAS over time. Conclusions: Recruitment for a large-scale trial of ACT is feasible. Challenges with remote data collection as well as participant burden during the COVID-19 pandemic resulted in lower than anticipated completion rates. Future studies should focus on decreasing participant burden and streamlining study procedures. Clinical Trials Registration: NCT05003362.

[Antipsychotic Treatment of Alcohol Withdrawal Syndrome with Focus on Delirium Tremens: a Systematic Review]. / Systematische Übersichtsarbeit Antipsychotische Behandlung des Alkoholentzugssyndroms: Fokus Delirium Tremens.

BACKGROUND: Delirium tremens (DT) is a common complication of alcohol withdrawal. Pharmacological treatment of hospitalized patients with DT is important in addiction medicine but also in other medical disciplines where DT can occur as a complication of hospitalization. Patients suffering from DT require treatment with benzodiazepines (short-acting benzodiazepines for elderly patients to reduce accumulation), and in cases of psychotic symptoms, treatment with antipsychotics. Benzodiazepines are a first-line treatment for DT. A specific guideline for the use of antipsychotics has yet to be developed. This review discusses the current guidelines and literature on the antipsychotic treatment options in DT. AIM: Systematic presentation of relevant antipsychotics for the treatment of DT. METHODS: A systematic literature search was conducted using Scopus and PubMed. The last search was conducted on May 22nd 2022. Original articles and reviews on antipsychotic treatment in alcohol withdrawal and DT were included in this review. Further, international guidelines were also considered. The review was registered using the PROSPERO database (https://www.crd.york.ac.uk/prospero/); CRD42021264611. RESULTS: Haloperidol is mainly recommended for use in the intensive care unit. There is little literature on the use of atypical antipsychotics to treat DT. Treatment with antipsychotics always should be combined with benzodiazepines, and physicians should watch out for complications like neuroleptic malignant syndrome, QTc interval prolongation, extrapyramidal symptoms and withdrawal seizures resulting from lowering the threshold for seizures. CONCLUSION: Antipsychotic treatment should depend on the experience of the physician. Beside haloperidol, no other clear recommendations are available.

Biofeedback EMG alternative therapy for chronic low back pain (the BEAT-pain study).

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<0.001). Conclusions: Virtual EMG biofeedback shows promise as a potential therapy for reducing pain and disability in individuals with chronic nonspecific low back pain.

Electromyography-biofeedback for chronic low back pain: A qualitative cohort study.

BACKGROUND AND AIMS: Surface electromyography-biofeedback (sEMG-BF) may reduce the burden of CLBP by improving physical functioning, sleep, pain catastrophizing, anxiety, and depression. This qualitative study investigated the impact of weekly EMG-BF sessions on adults with CLBP. METHODS: Twenty-six individuals with CLBP participated in telephone interviews after completing an 8-week virtual sEMG-BF intervention. Trained interviewers conducted the 10-to-15-minute semi-structured interviews to understand participants' experience with the intervention. Common themes and subthemes were identified and analyzed using MAXQDA 2022 software. RESULTS: Participants were predominantly middle-aged females (M = 45, range of 19 - 66) who have had exposure to utilizing conventional therapies such as physical therapy, chiropractor, and massage for the treatment of CLBP. This study focused on participants who reported their experience of the main outcome study which included perceived reductions in CLBP symptoms, including pain and stress, and positive effects on self-awareness and sleep. Three overarching themes emerged and were further divided into subthemes: participants' involvement (virtual experience, accessibility of device, and future recommendations) perceived benefits (participants gained awareness, recommendations for future treatment, met expectations, and implementation), and desire for flexibility (obstacles and COVID-19 Impact). No adverse effects were reported by any of the participants within the study. CONCLUSIONS: Both physical and psychological improvements were reported by participants following an sEMG-BF intervention. Specific implementation procedures and critical barriers were identified. In particular, the ability to receive care for CLBP during the COVID-19 pandemic was important to participants.

Acceptance and commitment therapy for episodic migraine: Rationale and design of a pilot randomized controlled trial.

Migraine is a debilitating disorder with limited pharmacological options. Many migraine medications can have intolerable side effects leading patients to seek complementary and integrative health (CIM) approaches for treatment. One option that is growing in popularity and evidence is Acceptance and Commitment Therapy (ACT), a mindfulness-based therapy. The purpose of this paper is to describe how ACT may be an effective modality integrated into the treatment of migraine and to describe the design of a pilot study of ACT for migraine. First, we review the research and the promise of mindfulness therapies for the treatment of migraine. Then, we describe how ACT differs from other mindfulness therapies for migraine and why it can be a promising option for these patients. Finally, we summarize the design of a pilot study designed to determine the feasibility of performing a future fully powered study to determine the effectiveness of ACT on migraine frequency and disability. This pilot study includes unique features, including a remotely-delivered ACT intervention and the measurement of cortisol levels before and after the intervention.

Exploring the Relationship Between Endogenous Pain Modulation, Pain Intensity, and Depression in Patients Using Opioids for Chronic Low Back Pain.

INTRODUCTION: Endogenous pain modulatory processes appear to play an important role in shaping pain-related outcomes, but we know relatively little about the influence of psychosocial factors on those pain modulatory processes. The primary objective of this study was to explore associations between endogenous pain modulation (ie, conditioned pain modulation, CPM; temporal summation, TS), chronic pain, and negative affective factors (ie, depression, anxiety symptoms) in a sample of participants with chronic low back pain (CLBP) treated with long-term daily opioids. METHODS: Adults with opioid-treated CLBP (N=107) completed questionnaires assessing pain, pain symptoms, and psychological measures. CPM and TS were evaluated as predictors of pain intensity ratings (Brief Pain Inventory), with depression scores (Hospital Anxiety and Depression Scale, depression subscale) examined as potential moderators of those associations. RESULTS: Moderation analyses demonstrated associations between CPM and back pain intensity ratings, moderated by depression symptom scores (B=-0.002, SE=0.0008, P<0.01) when controlling for daily opioid dose, with participants with higher depression scores showing a relatively stronger link between lower CPM and increased pain intensity ratings. Significant associations were observed between depression, pain intensity, and CPM-derived outcomes. CONCLUSION: Our findings suggest that reduced pain-inhibitory capacity is associated with elevated self-reported pain intensity in adults with opioid-treated CLBP, particularly among those with higher severity of depression symptoms.

Biofeedback EMG alternative therapy for chronic low back pain: Study protocol of a pilot randomized controlled trial.

BACKGROUND: Chronic pain affects about 100 million U.S. adults, with chronic low back pain (CLBP) cited as the most prevalent type. Although there is evidence that non-pharmacological therapies seem to be effective for treating low back pain, there is limited evidence of the effectiveness of EMG biofeedback with non-specific chronic low back pain (NCLBP). The purpose of this study is, therefore, to determine the efficacy of a portable EMG biofeedback device on pain in individuals with CLBP. METHODS/DESIGN: This study is a prospective, single-center, assessor-blind, two-arm, parallel randomized controlled trial to be conducted at Brigham and Women's Hospital, Boston, MA. Eighty patients with CLBP will be randomized in a 2:1 ratio to receive sEMG-BF (surface EMG biofeedback) or continued care (no intervention). All participants will receive treatment virtually weekly for 8 weeks. The primary outcome will be pain intensity (Brief Pain Inventory). The secondary outcomes will include pain interference (Brief Pain Inventory), disability (The Oswestry Disability Index (ODI)), anxiety and depression (Hospital Anxiety and Depression Scale). All outcomes will be assessed at baseline, immediately post-intervention, and 3 months follow-up. CONCLUSION: To our knowledge, this study will be the first powered randomized controlled trial to compare the effectiveness of a virtual sEMG-BF protocol specifically designed for CLBP. The outcome of the study may provide evidence for the effectiveness of biofeedback using digital therapeutics to relieve pain in individuals with CLBP. TRIAL REGISTRATION: Clinical Trials Registry (http://ClinicalTrials.gov Identifier: NCT04607460). Registered on October 29, 2020.

The impact of COVID-19 pandemic on mental and physical wellbeing in women with fibromyalgia: a longitudinal mixed-methods study.

OBJECTIVE: The COVID-19 pandemic has strongly influenced psychological and physical health worldwide. The aim of this study was to examine the impact of the pandemic on women with fibromyalgia. METHODS: This mixed methods pilot study explored measures of pain severity and interference, as well as pain catastrophizing and level of fibromyalgia impact among women with fibromyalgia before and during the COVID-19 pandemic in the USA. Fibromyalgia patients completed demographic, pain-related, and other validated psychosocial questionnaires prior to the onset of the COVID-19 pandemic, and then were re-assessed with those questionnaires, as well as a pandemic-related questionnaire assessing the impact of the pandemic on the patients' life, during the pandemic. RESULTS: When comparing data reported before the pandemic to data collected 3-6 months into the pandemic, women with fibromyalgia reported a general worsening of their pain and pain-related symptoms. During the pandemic, pain catastrophizing (p ≤ 0.05) and fibromyalgia impact (p ≤ 0.05) increased significantly compared to before the pandemic. The increase in pain catastrophizing scores was highly correlated with the impact of the pandemic on the participants' ability to cope with pain and on their mental health. Qualitative analysis corroborated the significant impact of the pandemic on patients' mental health, with the vast majority reporting a worsening of their mood. Other impacted domains included anxiety, level of activity and sleep. CONCLUSIONS: Collectively, the pandemic appears to have produced a substantive worsening of pain-related symptomatology among women with fibromyalgia, which should be addressed by targeted interventions.

Characteristics of antipsychotic drug-induced hypothermia in psychogeriatric inpatients.

OBJECTIVE: Hypothermia is a potentially lethal adverse reaction to typical and atypical antipsychotic drugs (APD). Among predisposing factors are advanced age and comorbid somatic diseases. The aim of this study was to assess the incidence of hypothermia and quantify risk factors. METHOD: Charts of N = 3002 psychogeriatric inpatients were screened for incidence of hypothermia (body core temperature <35.0°C). The frequency of hypothermia was compared between patients treated with versus without APD and, within the sample of APD-treated patients, for (1) specific APD, (2) sex, (3) main diagnosis, and (4) age. RESULTS: N = 54 cases (2.6%) of hypothermia occurred in APD-treated patients and 12 cases (1.3%) in non-APD-treated patients (p = 0.024). In APD-treated patients, only male sex (p = 0.038) and pipamperone were associated with a higher incidence of hypothermia (p = 0.0017). Whereas the main diagnosis delirium showed a trend to significance, age did not correlate with hypothermia. CONCLUSION: Medication with pipamperone was associated with an increased risk of hypothermia. The advanced age of our sample might as well explain the high incidence of hypothermia within our sample and the failure to detect high age as a risk factor due to a ceiling effect.

Dynamic Functional Brain Connectivity Underlying Temporal Summation of Pain in Fibromyalgia.

OBJECTIVE: Abnormal central pain processing is a leading cause of pain in fibromyalgia (FM) and is perceptually characterized with the psychophysical measure of temporal summation of pain (TSP). TSP is the perception of increasingly greater pain in response to repetitive or tonic noxious stimuli. Previous neuroimaging studies have used static (i.e., summary) measures to examine the functional magnetic resonance imaging (fMRI) correlates of TSP in FM. However, functional brain activity rapidly and dynamically reorganizes over time, and, similarly, TSP is a temporally evolving process. This study was undertaken to demonstrate how a complete understanding of the neural circuitry supporting TSP in FM thus requires a dynamic measure that evolves over time. METHODS: We utilized novel methods for analyzing dynamic functional brain connectivity in patients with FM in order to examine how TSP-associated fluctuations are linked to the dynamic functional reconfiguration of the brain. In 84 FM patients and age- and sex-matched healthy controls, we collected high-temporal-resolution fMRI data during a resting state and during a state in which sustained cuff pressure pain was applied to the leg. RESULTS: FM patients experienced greater TSP than healthy controls (mean ± SD TSP score 17.93 ± 19.24 in FM patients versus 9.47 ± 14.06 in healthy controls; P = 0.028), but TSP scores varied substantially between patients. In the brain, the presence versus absence of TSP in patients with FM was marked by more sustained enmeshment between sensorimotor and salience networks during the pain period. Furthermore, dynamic enmeshment was noted solely in FM patients with high TSP, as interactions with all other brain networks were dampened during the pain period. CONCLUSION: This study elucidates the dynamic brain processes underlying facilitated central pain processing in FM. Our findings will enable future investigation of dynamic symptoms in FM.

The "self" in pain: high levels of schema-enmeshment worsen fibromyalgia impact.

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 < 0.001). CONCLUSIONS: Our results indicate that schema-enmeshment is associated with greater intrusiveness of chronic pain on everyday life, thereby posing significant limitations on the emotional and physical well-being of fibromyalgia patients. Schema-enmeshment also appears to partly account for the deleterious effect of pain catastrophizing on disease impact. The PRISM is a simple tool that may uniquely capture the extent to which chronic pain and illness infiltrates and affects one's self-concept.

Psychophysiologic symptom relief therapy for chronic back pain: a pilot randomized controlled trial.

INTRODUCTION: Chronic back pain is the leading cause of disability in the United States. Based on the hypothesis that nonspecific back pain may be rooted in a psychophysiologic etiology, we propose a new approach to chronic back pain. OBJECTIVES: A pilot study was conducted to assess whether psychophysiologic symptom relief therapy (PSRT) can reduce disability and back pain bothersomeness for patients with chronic back pain. METHODS: This was a three-armed, randomized trial for adults with nonspecific chronic back pain that compared PSRT with usual care and an active comparator (mindfulness-based stress reduction [MBSR]). Psychophysiologic symptom relief therapy-randomized participants received a 12-week (36 hours) course based on the psychophysiological model of pain. All groups were administered validated questionnaires at baseline and at 4, 8, 13, and 26 weeks. The primary outcome was the reduction in pain disability measured by the Roland-Morris Disability Questionnaire. RESULTS: The mean Roland-Morris Disability Questionnaire score for the PSRT group (n = 11) decreased from 9.5 (±4.3 SDs) to 3.3 (±5.1) after 26 weeks which was statistically significant compared with both MBSR (n = 12) (P = 0.04) and usual care (n = 12) (P = 0.03). Pain bothersomeness scores and pain-related anxiety decreased significantly over 26 weeks in PSRT compared with MBSR and usual care (data in manuscript). At 26 weeks, 63.6% of the PSRT arm reported being pain free (0/10 pain) compared with 25.0% and 16.7% in MBSR and usual care arms, respectively. Psychophysiologic symptom relief therapy attendance was 76%, and there was 100% follow-up of all groups. CONCLUSION: Psychophysiologic symptom relief therapy is a feasible and potentially highly beneficial treatment for patients with nonspecific back pain.

Individual variation in diurnal cortisol in patients with knee osteoarthritis: Clinical correlates.

BACKGROUND: The cortisol awakening response (CAR) is a core biomarker of hypothalamic-pituitary-adrenal (HPA) axis regulation. To date, however, studies of HPA-axis function among patients with chronic pain are scarce and show equivocal results. The objectives of this study were to investigate the association between CAR and pain-related outcomes and to investigate potential sex differences in patients with knee osteoarthritis (KOA). METHODS: In this cross-sectional study, KOA patients (N = 96) completed self-report questionnaires assessing pain and psychosocial factors and underwent Quantitative Sensory Testing (QST) to assess pressure pain threshold (PPT). Additionally, salivary cortisol samples (N = 60) were collected to assess HPA-axis function at 6 time points (awakening, 15- and 30-minute post-awakening, 4 PM, 9 PM and bedtime). The CAR was calculated by examining increases in salivary cortisol from awakening to 30 min post awakening and the total post-awakening cortisol concentration by calculating the lower areas under the curve of cortisol with respect to ground (AUCG). RESULTS: Patients with a relatively blunted CAR had significantly higher anxiety levels and lower PPT than patients with relatively normal CAR. Similarly, patients with a relatively reduced AUCG had significantly higher pain interference and anxiety levels compared to patients with relatively normal AUCG. PPT was positively correlated with CAR and AUCG and negatively correlated with pain severity and anxiety. Men with KOA had significantly lower anxiety, higher PPT and higher CAR and AUCG than women with KOA. Mediation analysis results revealed a significant indirect effect of PPT on the relationship between sex and AUCG. CONCLUSIONS: The findings of this study suggest that neuroendocrine factors such as CAR and AUCG may contribute to individual differences in pain-related outcomes in patients with KOA. Additionally, our results show sex differences in the magnitude of morning HPA activation and pain-related outcomes. Finally, our findings are suggestive of a sex-dependent relationship between post-awakening cortisol concentrations and pain perception. Future research should examine these associations across various pain populations.

3D magnetic resonance spectroscopic imaging reveals links between brain metabolites and multidimensional pain features in fibromyalgia.

BACKGROUND: Fibromyalgia is a centralized multidimensional chronic pain syndrome, but its pathophysiology is not fully understood. METHODS: We applied 3D magnetic resonance spectroscopic imaging (MRSI), covering multiple cortical and subcortical brain regions, to investigate the association between neuro-metabolite (e.g. combined glutamate and glutamine, Glx; myo-inositol, mIno; and combined (total) N-acetylaspartate and N-acetylaspartylglutamate, tNAA) levels and multidimensional clinical/behavioural variables (e.g. pain catastrophizing, clinical pain severity and evoked pain sensitivity) in women with fibromyalgia (N = 87). RESULTS: Pain catastrophizing scores were positively correlated with Glx and tNAA levels in insular cortex, and negatively correlated with mIno levels in posterior cingulate cortex (PCC). Clinical pain severity was positively correlated with Glx levels in insula and PCC, and with tNAA levels in anterior midcingulate cortex (aMCC), but negatively correlated with mIno levels in aMCC and thalamus. Evoked pain sensitivity was negatively correlated with levels of tNAA in insular cortex, MCC, PCC and thalamus. CONCLUSIONS: These findings support single voxel placement targeting nociceptive processing areas in prior 1 H-MRS studies, but also highlight other areas not as commonly targeted, such as PCC, as important for chronic pain pathophysiology. Identifying target brain regions linked to multidimensional symptoms of fibromyalgia (e.g. negative cognitive/affective response to pain, clinical pain, evoked pain sensitivity) may aid the development of neuromodulatory and individualized therapies. Furthermore, efficient multi-region sampling with 3D MRSI could reduce the burden of lengthy scan time for clinical research applications of molecular brain-based mechanisms supporting multidimensional aspects of fibromyalgia. SIGNIFICANCE: This large N study linked brain metabolites and pain features in fibromyalgia patients, with a better spatial resolution and brain coverage, to understand a molecular mechanism underlying pain catastrophizing and other aspects of pain transmission. Metabolite levels in self-referential cognitive processing area as well as pain-processing regions were associated with pain outcomes. These results could help the understanding of its pathophysiology and treatment strategies for clinicians.

Modifiable Psychological Factors Affecting Functioning in Fibromyalgia.

OBJECTIVE: To examine the role of several interrelated, potentially modifiable psychological factors (i.e., mindfulness and catastrophizing) in influencing patient-reported functioning. METHODS: In this cross-sectional study, 107 patients with fibromyalgia completed self-report assessments of pain severity, functioning and impact of symptoms, mindfulness, and pain catastrophizing. Linear regression and bootstrapping mediation analyses were performed to assess the relationships between these factors. RESULTS: Pain intensity was significantly and positively associated with pain catastrophizing and impact of fibromyalgia on functioning. Linear regression analyses indicated that pain intensity, catastrophizing, and mindfulness affect functioning in fibromyalgia. Follow-up mediation analysis revealed a significant indirect effect of pain catastrophizing on the relationship between pain intensity and fibromyalgia functioning. CONCLUSION: Individuals with fibromyalgia who have higher levels of pain and catastrophizing, and lower levels of mindfulness, are more likely to experience impaired functioning. Our findings suggest that pain catastrophizing appears to be an especially important variable contributing to reduced functioning in women with fibromyalgia. Therefore, catastrophizing-reducing treatments (e.g., cognitive behavioral therapy) are likely to have direct, beneficial impacts on functioning.

A picture is worth a thousand words: linking fibromyalgia pain widespreadness from digital pain drawings with pain catastrophizing and brain cross-network connectivity.

ABSTRACT: Pain catastrophizing is prominent in chronic pain conditions such as fibromyalgia and has been proposed to contribute to the development of pain widespreadness. However, the brain mechanisms responsible for this association are unknown. We hypothesized that increased resting salience network (SLN) connectivity to nodes of the default mode network (DMN), representing previously reported pain-linked cross-network enmeshment, would be associated with increased pain catastrophizing and widespreadness across body sites. We applied functional magnetic resonance imaging (fMRI) and digital pain drawings (free-hand drawing over a body outline, analyzed using conventional software for multivoxel fMRI analysis) to investigate precisely quantified measures of pain widespreadness and the associations between pain catastrophizing (Pain Catastrophizing Scale), resting brain network connectivity (Dual-regression Independent Component Analysis, 6-minute multiband accelerated fMRI), and pain widespreadness in fibromyalgia patients (N = 79). Fibromyalgia patients reported pain in multiple body areas (most frequently the spinal region, from the lower back to the neck), with moderately high pain widespreadness (mean ± SD: 26.1 ± 24.1% of total body area), and high pain catastrophizing scale scores (27.0 ± 21.9, scale range: 0-52), which were positively correlated (r = 0.26, P = 0.02). A whole-brain regression analysis focused on SLN connectivity indicated that pain widespreadness was also positively associated with SLN connectivity to the posterior cingulate cortex, a key node of the DMN. Moreover, we found that SLN-posterior cingulate cortex connectivity statistically mediated the association between pain catastrophizing and pain widespreadness (P = 0.01). In conclusion, we identified a putative brain mechanism underpinning the association between greater pain catastrophizing and a larger spatial extent of body pain in fibromyalgia, implicating a role for brain SLN-DMN cross-network enmeshment in mediating this association.