Heterogeneity of psychophysiological stress responses in fibromyalgia syndrome patients

Dysregulated psychophysiological responses have been observed in patients with fibromyalgia syndrome (FMS), although the results are inconsistent. Surface electromyographic (EMG), systolic and diastolic blood pressure, heart rate (HR), and skin conductance levels (SCLs) were continuously recorded at baseline, and during a series of stress and relaxation tasks in 90 FMS patients and 30 age and sex matched healthy controls (HCs). The patient sample demonstrated lower baseline EMG levels compared to the HCs on all tasks. In contrast, the patients displayed elevated HR and SCL (sympathetic vasomotor and sudomotor indices, respectively) during both stress tasks. A cluster analysis identified four psychophysiological response patterns: 63.3% of HCs showed increased muscle tension and stable cardiovascular responses; 34.8% of FMS patients showed a pattern of increased sympathetic vasomotor reactivity with stable sudomotor and reduced muscular response; 12.2% of FMS patients showed a pattern of increased sympathetic sudomotor reactivity connected with increased sympathetic vasomotor response and reduced muscular response; and, in contrast, 46.7% of FMS patients showed a pattern of parasympathetic vasomotor reactivity and reduced sudomotor as well as muscular response. The identification of low baseline muscle tension in FMS is discrepant with other chronic pain syndromes and suggests that unique psychophysiological features may be associated with FMS. The different psychophysiological response patterns within the patient sample support the heterogeneity of FMS

Psychological pain treatment in fibromyalgia syndrome: efficacy of operant behavioural and cognitive behavioural treatments

The present study focused on the evaluation of the effects of operant behavioural (OBT) and cognitive behavioural (CBT) treatments for fibromyalgia syndrome (FMS). One hundred and twenty-five patients who fulfilled the American College of Rheumatology criteria for FMS were randomly assigned to OBT (n = 43), CBT (n = 42), or an attention-placebo (AP) treatment (n = 40) that consisted of discussions of FMS-related problems. Assessments of physical functioning, pain, affective distress, and cognitive and behavioural variables were performed pre-treatment and post-treatment as well as 6 and 12 months post-treatment. Patients receiving the OBT or CBT reported a significant reduction in pain intensity post-treatment (all Fs > 3.89, all Ps < 0.01). In addition, the CBT group reported statistically significant improvements in cognitive (all Fs > 7.95, all P < 0.01) and affective variables (all Fs > 2.99, all Ps < 0.02), and the OBT group demonstrated statistically significant improvements in physical functioning and behavioural variables (all Fs > 5.99, all Ps < 0.001) compared with AP. The AP group reported no significant improvement but actually deterioration in the outcome variables. The post-treatment effects for the OBT and CBT groups were maintained at both the 6- and 12-month follow-ups. These results suggest that both OBT and CBT are effective in treating patients with FMS with some differences in the outcome measures specifically targeted by the individual treatments compared with an unstructured discussion group. The AP group showed that unstructured discussion of FMS-related problems may be detrimental

An internet survey of 2,596 people with fibromyalgia

BACKGROUND: This study explored the feasibility of using an Internet survey of people with fibromyalgia (FM), with a view to providing information on demographics, sources of information, symptoms, functionality, perceived aggravating factors, perceived triggering events, health care utilization, management strategies, and medication use. METHODS: A survey questionnaire was developed by the National Fibromyalgia Association (NFA) in conjunction with a task force of "experts in the field". The questionnaire underwent several rounds of testing to improve its face validity, content validity, clarity and readability before it was mounted on the internet. The questionnaire consisted of 121 items and is available online at the website of the National Fibromyalgia Association. RESULTS: The questionnaire was completed by 2,569 people. Most were from the United States, with at least one respondent from each of the 50 states. Respondents were predominantly middle-aged Caucasian females, most of whom had FM symptoms for ≥ 4 years. The most common problems were morning stiffness, fatigue, nonrestorative sleep, pain, concentration, and memory. Aggravating factors included: emotional distress, weather changes, insomnia, and strenuous activity. Respondents rated the most effective management modalities as rest, heat, pain medications, antidepressants, and hypnotics. The most commonly used medications were: acetaminophen, ibuprofen, naproxen, cyclobenzaprine, amitriptyline, and aspirin. The medications perceived to be the most effective were: hydrocodone preparations, aprazolam, oxycodone preparations, zolpidem, cyclobenzaprine, and clonazepam. CONCLUSION: This survey provides a snap-shot of FM at the end of 2005, as reported by a self-selected population of people. This descriptive data has a heuristic function, in that it identifies several issues for further research, such as the prescribing habits of FM health care providers, the role of emotional precipitants, the impact of obesity, the significance of low back pain and the nature of FM related stiffness

Predictive value of fear avoidance in developing chronic neck pain disability: consequences for clinical decision making

Objective\ud To improve clinical decision making in posttraumatic neck pain by investigating the additional value of fear-avoidance variables in predicting chronic neck pain disability.\ud \ud Design\ud An inception cohort with baseline assessment 1 week posttrauma and outcome assessment 24 weeks posttrauma. Predictive factors include pain intensity, Neck Disability Index (NDI), catastrophizing, fear of movement (Tampa Scale for Kinesiophobia [TSK]), and avoidance muscle behavior.\ud \ud Setting\ud Hospital emergency department of a general hospital.\ud \ud Participants\ud A consecutive sample of 90 people reporting of pain in neck or head region after a motor vehicle collision. Eighty-two subjects (91.1%) of the sample provided 24-week follow-up on the outcome.\ud \ud Interventions\ud Not applicable.\ud \ud Main outcome measure\ud The NDI assessing physical disability of subjects with neck pain.\ud \ud Results\ud By using a combination of the baseline NDI and TSK, it appears to be possible to predict chronic disability with a probability of 54.3% (95% confidence interval [CI], 35.2%–72.3%) after entering the NDI (cutoff, 15) as a first test, and with a probability of 83.3% (95% CI, 70.3%–91.3%) after entering the TSK (cutoff, 40) in a second test.\ud \ud Conclusions\ud A simple rating of baseline neck pain disability within a week of the trauma, separately or in combination with a test for fear of movement, can be used to predict future outcome. Patients showing fear of movement can be offered an intervention that focuses on reduction of this fear.\ud \u

An examination of the psychometric structure of the Multidimensional Pain Inventory in temporomandibular disorder patients: a confirmatory factor analysis

BACKGROUND: This paper seeks to analyse the psychometric and structural properties of the Multidimensional Pain Inventory (MPI) in a sample of temporomandibular disorder patients. METHODS: The internal consistency of the scales was obtained. Confirmatory Factor Analysis was carried out to test the MPI structure section by section in a sample of 114 temporomandibular disorder patients. RESULTS: Nearly all scales obtained good reliability indexes. The original structure could not be totally confirmed. However, with a few adjustments we obtained a satisfactory structural model of the MPI which was slightly different from the original: certain items and the Self control scale were eliminated; in two cases, two original scales were grouped in one factor, Solicitous and Distracting responses on the one hand, and Social activities and Away from home activities, on the other. CONCLUSION: The MPI has been demonstrated to be a reliable tool for the assessment of pain in temporomandibular disorder patients. Some divergences to be taken into account have been clarified

Pain measurement in rheumatic and musculoskeletal diseases: where to go from here? Report from a Special Interest Group at OMERACT 2018

Objective: Establishing a research agenda on standardizing pain measurement in clinical trials in rheumatic and musculoskeletal diseases (RMDs). Methods: Discussion during a meeting at OMERACT 2018, prepared by a systematic review of existing core outcome sets and a patient online survey. Results: Several key questions were debated: is pain a symptom or a disease? are pain core (sub)domains consistent across RMDs? how to account for pain mechanistic descriptors (e.g. central sensitization) in pain measurement? Conclusion: Characterizing and assessing the spectrum of pain experience across RMDs in a standardized fashion is the future objective of the OMERACT pain working group

International, multidisciplinary Delphi consensus recommendations on non-pharmacological interventions for fibromyalgia

Funding Information: The Republic of Turkey Ministry of National Education for the PhD studentship. Publisher Copyright: © 2022 The Author(s)Objectives: To develop evidence-based expert recommendations for non-pharmacological treatments for pain, fatigue, sleep problems, and depression in fibromyalgia. Methods: An international, multidisciplinary Delphi exercise was conducted. Authors of EULAR and the Canadian Fibromyalgia Guidelines Group, members of the American Pain Society and clinicians with expertise in fibromyalgia were invited. Participants were asked to select non-pharmacological interventions that could be offered for specific fibromyalgia symptoms and to classify them as either core or adjunctive treatments. An evidence summary was provided to aid the decision making. Items receiving >70% votes were accepted, those receiving <30% votes were rejected and those obtaining 30-70% votes were recirculated for up to two additional rounds. Results: Seventeen experts participated (Europe (n = 10), North America (n = 6), and Israel (n = 1)) in the Delphi exercise and completed all three rounds. Aerobic exercise, education, sleep hygiene and cognitive behavioural therapy were recommended as core treatments for all symptoms. Mind-body exercises were recommended as core interventions for pain, fatigue and sleep problems. Mindfulness was voted core treatment for depression, and adjunctive treatment for other symptoms. Other interventions, namely music, relaxation, hot bath, and local heat were voted as adjunctive treatments, varying between symptoms. Conclusions: This study provided evidence-based expert consensus recommendations on non-pharmacological treatments for fibromyalgia that may be used to individualise treatments in clinical practice targeting the diverse symptoms associated with fibromyalgia.publishersversionepub_ahead_of_prin

Designed Inhibitors of Insulin-Degrading Enzyme Regulate the Catabolism and Activity of Insulin

Background: Insulin is a vital peptide hormone that is a central regulator of glucose homeostasis, and impairments in insulin signaling cause diabetes mellitus. In principle, it should be possible to enhance the activity of insulin by inhibiting its catabolism, which is mediated primarily by insulin-degrading enzyme (IDE), a structurally and evolutionarily distinctive zinc-metalloprotease. Despite interest in pharmacological inhibition of IDE as an attractive anti-diabetic approach dating to the 1950s, potent and selective inhibitors of IDE have not yet emerged. Methodology/Principal Findings: We used a rational design approach based on analysis of combinatorial peptide mixtures and focused compound libraries to develop novel peptide hydroxamic acid inhibitors of IDE. The resulting compounds are ∼106 times more potent than existing inhibitors, non-toxic, and surprisingly selective for IDE vis-à-vis conventional zinc-metalloproteases. Crystallographic analysis of an IDE-inhibitor complex reveals a novel mode of inhibition based on stabilization of IDE's “closed,” inactive conformation. We show further that pharmacological inhibition of IDE potentiates insulin signaling by a mechanism involving reduced catabolism of internalized insulin. Conclusions/Significance: The inhibitors we describe are the first to potently and selectively inhibit IDE or indeed any member of this atypical zinc-metalloprotease superfamily. The distinctive structure of IDE's active site, and the mode of action of our inhibitors, suggests that it may be possible to develop inhibitors that cross-react minimally with conventional zinc-metalloproteases. Significantly, our results reveal that insulin signaling is normally regulated by IDE activity not only extracellularly but also within cells, supporting the longstanding view that IDE inhibitors could hold therapeutic value for the treatment of diabetes

Patient engagement in designing, conducting, and disseminating clinical pain research : IMMPACT recommended considerations

The consensus recommendations are based on the views of IMMPACT meeting participants and do not necessarily represent the views of the organizations with which the authors are affiliated. The following individuals made important contributions to the IMMPACT meeting but were not able to participate in the preparation of this article: David Atkins, MD (Department of Veterans Affairs), Rebecca Baker, PhD (National Institutes of Health), Allan Basbaum, PhD (University of California San Francisco), Robyn Bent, RN, MS (Food and Drug Administration), Nathalie Bere, MPH (European Medicines Agency), Alysha Croker, PhD (Health Canada), Stephen Bruehl, PhD (Vanderbilt University), Michael Cobas Meyer, MD, MBS (Eli Lilly), Scott Evans, PhD (George Washington University), Gail Graham (University of Maryland), Jennifer Haythornthwaite, PhD (Johns Hopkins University), Sharon Hertz, MD (Hertz and Fields Consulting), Jonathan Jackson, PhD (Harvard Medical School), Mark Jensen, PhD (University of Washington), Francis Keefe, PhD (Duke University), Karim Khan, MD, PhD, MBA (Canadian Institutes of Health Research), Lynn Laidlaw (University of Aberdeen), Steven Lane (Patient-Centered Outcomes Research Institute), Karen Morales, BS (University of Maryland), David Leventhal, MBA (Pfizer), Jeremy Taylor, OBE (National Institute for Health Research), and Lena Sun, MD (Columbia University). The manuscript has not been submitted, presented, or published elsewhere. Parts of the manuscript have been presented in a topical workshop at IASP World Congress on Pain in Toronto, in 2022.Peer reviewedPublisher PD