Tag: chronic pain

Chronic Overlapping Pain Conditions in people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a sample from the Multi-site Clinical Assessment of ME/CFS (MCAM) study

Abstract:

Background: Chronic overlapping pain conditions (COPCs), pain-related conditions that frequently occur together, may occur in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and could impact illness severity. This study aimed to identify comorbid COPCs in patients with ME/CFS and evaluate their impact on illness severity.

Methods: We used data from 923 participants in the Multi-Site Clinical Assessment of ME/CFS study, conducted in seven U.S. specialty clinics between 2012 and 2020, who completed the baseline assessment (595 ME/CFS and 328 healthy controls (HC)). COPCs included chronic low back pain (cLBP), chronic migraine/headache (cMHA), fibromyalgia (FM), interstitial cystitis/irritable bladder (IC/IB), irritable bowel syndrome (IBS), temporomandibular disorder (TMD). Illness severity was assessed through questionnaires measuring symptoms and functioning. Multivariate analysis of variance and analysis of covariance models were used for analyses. Log-binomial regression analyses were used to compute prevalence of COPCs and prevalence ratios (PR) between groups with 95% confidence intervals. Both unadjusted and adjusted results with age and sex are presented.

Results: 76% of participants with ME/CFS had at least one COPCs compared to 17.4% of HC. Among ME/CFS participants, cMHA was most prevalent (48.1%), followed by FM (45.0%), cLBP (33.1%), and IBS (31.6%). All individual COPCs, except TMD, were significantly more frequent in females than males. The unadjusted PR (ME/CFS compared to HC) was highest for FM [147.74 (95% confidence interval (CI) = 20.83-1047.75], followed by cLBP [39.45 (12.73-122.27)], and IC/IB [13.78 (1.88-101.24)]. The significance and order did not change after age and sex adjustment. The COPC comorbidities of cLBP and FM each had a significant impact on most health measures, particularly in pain attributes (Cohen’s d effect size 0.8 or larger). While the impact of COPC comorbidities on non-pain attributes and quality of life measures was less pronounced than that on pain, statistically significant differences between ME/CFS participants with and without COPCs were still evident.

Conclusions: More than 75% of ME/CFS participants had one or more COPCs. Multiple COPCs further exacerbated illness severity, especially among females with ME/CFS. Assessment and management of COPCs may help improve the health and quality of life for patients with ME/CFS.

Source: Fall EA, Chen Y, Lin JS, Issa A, Brimmer DJ, Bateman L, Lapp CW, Podell RN, Natelson BH, Kogelnik AM, Klimas NG, Peterson DL, Unger ER; MCAM Study Group. Chronic Overlapping Pain Conditions in people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a sample from the Multi-site Clinical Assessment of ME/CFS (MCAM) study. BMC Neurol. 2024 Oct 18;24(1):399. doi: 10.1186/s12883-024-03872-0. PMID: 39425035; PMCID: PMC11488184. https://pmc.ncbi.nlm.nih.gov/articles/PMC11488184/ (Full text)

Widespread Myalgia and Chronic Fatigue: Phagocytes from Macrophagic Myofasciitis Patients Exposed to Aluminum Oxyhydroxide-Adjuvanted Vaccine Exhibit Specific Inflammatory, Autophagic, and Mitochondrial Responses

Abstract:

(1) Background: Macrophagic myofasciitis (MMF) is an inflammatory histopathological lesion demonstrating long-term biopersistence of vaccine-derived aluminum adjuvants within muscular phagocytic cells. Affected patients suffer from widespread myalgia and severe fatigue consistent with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a poorly understood disorder suspected to result from chronic immune stimulation by infectious and inorganic particles.

(2) Methods: In this study we determined the immuno-metabolic properties of MMF phagocytic cells compared to controls, at rest and upon exposure to aluminum oxyhydroxide adjuvant, with or without adsorbed antigens, using protein quantification and an oxygen consumption assay.

(3) Results: MMF and control cells similarly internalized the adjuvant and vaccine but MMF cells specifically expressed Rubicon and Nox2, two molecules unique to the LC3-associated phagocytosis (LAP) machinery, a non-canonical autophagic pathway able to downregulate canonical autophagy. MMF cells exhibited an altered inflammatory secretome, producing more pain-inducing CXC chemokines and less TNF-α than controls, consistent with chronic myalgia and exhaustion of the immune system previously documented in ME/CFS. MMF cells exhibited mitochondrial metabolism dysfunction, with exacerbated reaction to adjuvanted vaccine, contrasting with limited spare respiratory capacity and marked proton leak weakening energy production.

(4) Conclusions: MMF phagocytes seemingly use LAP to handle aluminum oxyhydroxide vaccine particles, secrete pain-inducing molecules, and exhibit exacerbated metabolic reaction to the vaccine with limited capacity to respond to ongoing energetic requests.

Source: Masson JD, Badran G, Gherardi RK, Authier FJ, Crépeaux G. Widespread Myalgia and Chronic Fatigue: Phagocytes from Macrophagic Myofasciitis Patients Exposed to Aluminum Oxyhydroxide-Adjuvanted Vaccine Exhibit Specific Inflammatory, Autophagic, and Mitochondrial Responses. Toxics. 2024 Jul 4;12(7):491. doi: 10.3390/toxics12070491. PMID: 39058143. https://www.mdpi.com/2305-6304/12/7/491 (Full text)

Patients with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain report similar level of sickness behavior as individuals injected with bacterial endotoxin at peak inflammation

Abstract:

Background: Chronic sickness behavior is implicated in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain but the level of subjective sickness behavior in these conditions has not been investigated or compared to other clinical and non-clinical samples, or to the level in experimental inflammation. Furthermore, the relationship between sickness behavior and self-rated health and functioning is not known in patients with ME/CFS and chronic pain. The aim of the present study was to investigate how sickness behavior in patients with chronic conditions differs from that in individuals with experimental acute sickness, primary care patients, the general population and healthy subjects. In addition, we wanted to explore how sickness behavior is related to self-rated health and health-related functioning.

Methods: Sickness behavior was quantified using the sickness questionnaire (SicknessQ). Self-ratings were collected at one time-point in 6 different samples. Levels of sickness behavior in patients with ME/CFS (n ​= ​38) and patients with chronic pain (n ​= ​190) were compared to healthy subjects with lipopolysaccharide(LPS)-induced inflammation (n ​= ​29), primary care patients (n ​= ​163), individuals from the general population (n ​= ​155) and healthy subjects (n ​= ​48), using linear regression. Correlations and moderated regression analyses were used to investigate associations between sickness behavior and self-rated health and health-related functioning in ME/CFS, chronic pain and the general population.

Results: LPS-injected individuals (M ​= ​16.3), patients with ME/CFS (M ​= ​16.1), chronic pain (M ​= ​16.1) and primary care patients (M ​= ​10.7) reported significantly higher SicknessQ scores than individuals from the general population (M ​= ​5.4) and healthy subjects (M ​= ​3.6) all p‘s ​< ​0.001). In turn, LPS-injected individuals, patients with ME/CFS and chronic pain reported significantly higher SicknessQ scores than primary care patients (p’s ​< ​0.01). Higher levels of sickness behavior were associated with poorer self-rated health and health-related functioning (p’s ​< ​0.01), but less so in patients with ME/CFS and chronic pain than in individuals from the general population.

Conclusions: Patients with ME/CFS and chronic pain report similar high levels of sickness behavior; higher than primary care patients, and comparable to levels in experimental inflammation. Further study of sickness behavior in ME/CFS and chronic pain populations is warranted as immune-to-brain interactions and sickness behavior may be of importance for functioning as well as in core pathophysiological processes in subsets of patients.

Source: Jonsjö MA, Åström J, Jones MP, Karshikoff B, Lodin K, Holmström L, Agréus L, Wicksell RK, Axelsson J, Lekander M, Olsson GL, Kemani M, Andreasson A. Patients with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain report similar level of sickness behavior as individuals injected with bacterial endotoxin at peak inflammation. Brain Behav Immun Health. 2019 Dec 17;2:100028. doi: 10.1016/j.bbih.2019.100028. PMID: 38377418; PMCID: PMC8474484. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474484/ (Full text)

DNA Methylation Changes in Blood Cells of Fibromyalgia and Chronic Fatigue Syndrome Patients

Abstract:

Purpose: Fibromyalgia (FM) and Chronic Fatigue Syndrome (CFS) affect 0.4% and 1% of society, respectively, and the prevalence of these pain syndromes is increasing. To date, no strong association between these syndromes and the genetic background of affected individuals has been shown. Therefore, it is plausible that epigenetic changes might play a role in the development of these syndromes.

Patients and Methods: Three previous studies have attempted to elaborate the involvement of genome-wide methylation changes in blood cells in the development of fibromyalgia and chronic fatigue syndrome. These studies included 22 patients with fibromyalgia and 127 patients with CFS, and the results of the studies were largely discrepant. Contradicting results of those studies may be attributed to differences in the omics data analysis approaches used in each study. We reanalyzed the data collected in these studies using an updated and coherent data-analysis framework.

Results: Overall, the methylation changes that we observed overlapped with previous results only to some extent. However, the gene set enrichment analyses based on genes annotated to methylation changes identified in each of the analyzed datasets were surprisingly coherent and uniformly associated with the physiological processes that, when affected, may result in symptoms characteristic of fibromyalgia and chronic fatigue syndrome

Conclusion: Methylomes of the blood cells of patients with FM and CFS in three independent studies have shown methylation changes that appear to be implicated in the pathogenesis of these syndromes.

Source: Przybylowicz PK, Sokolowska KE, Rola H, Wojdacz TK. DNA Methylation Changes in Blood Cells of Fibromyalgia and Chronic Fatigue Syndrome Patients. J Pain Res. 2023;16:4025-4036 https://doi.org/10.2147/JPR.S439412 https://www.dovepress.com/dna-methylation-changes-in-blood-cells-of-fibromyalgia-and-chronic-fat-peer-reviewed-fulltext-article-JPR (Full text)

Interdisciplinary multimodal pain therapy in postviral syndromes and ME/CFS : Features, pitfalls and model concept

Abstract:

in English, German

Background: Multimodal pain therapy usually take place in the context of group therapy lasting several weeks and is based on a generally activating approach. Due to the specificity of stress intolerance with postexertional malaise (PEM) in patients with postviral syndromes, physical as well as psychological overload must be urgently avoided in these cases; however, these aspects can only be insufficiently considered in current medical pain therapy concepts.

Methods: Summary of the current literature and presentation of clinical characteristics as well as presentation of a model project for a multimodal pain therapy in postviral syndromes with PEM.

Model concept: The presented model project describes a day clinic treatment setting for interdisciplinary multimodal pain therapy adapted to the individual resilience with minimization of the risk of strain-induced deterioration of the condition.

Source: Luchting B, Behrends U, Eigner B, Stojanov S, Warlitz C, Haegele M, Neuwirth E, Mihatsch L, Richter HP. Interdisziplinäre multimodale Schmerztherapie bei postviralen Syndromen und ME/CFS : Besonderheiten, Fallstricke und Modellkonzept [Interdisciplinary multimodal pain therapy in postviral syndromes and ME/CFS : Features, pitfalls and model concept]. Schmerz. 2023 Oct 20. German. doi: 10.1007/s00482-023-00761-2. Epub ahead of print. PMID: 37 https://pubmed.ncbi.nlm.nih.gov/37864020/864020.

A population-based investigation into the prevalence of chronic fatigue syndrome in United States military Veterans with chronic pain

Abstract:

Objective: Chronic fatigue syndrome (CFS) is a debilitating illness characterized by persistent fatigue among other symptoms. Pain symptoms are common and included in the diagnostic criteria for CFS but are not required for diagnosis. Despite the association between CFS and pain, few studies have examined CFS in the context of chronic pain (CP) conditions. The current study estimates the period prevalence of comorbid CFS among military Veterans with CP and compares sociodemographic characteristics and CP conditions of Veterans with CP + CFS to those with CP without CFS.

Methods: This study included Veterans Health Administration (VHA) data on 2,261,030 patients with chronic pain in 2018. Sociodemographic characteristics included age, sex, race, ethnicity, and rurality. Descriptive statistics were used to describe the sample and between-group comparisons included independent samples t-tests and chi-square tests of independence. Effect sizes were also examined.

Results: A total of 15,248 (0.67%) of Veterans with CP also had a diagnosis of CFS. Veterans diagnosed with CP + CFS were younger and were more likely to be female, White, non-Hispanic, and rural-dwelling. However, small and weak effect sizes were observed for these differences. The majority of Veterans with CP + CFS had limb/extremity (69.20%) back pain (53.44%), or abdominal/bowel pain (24.11%).

Conclusion: CDC treatment recommendations for CFS include treating pain first, studying CFS in the context of CP is critically important. Veterans diagnosed with CP + CFS appear demographically similar, compared to Veterans with CP without CFS. Examining the utilization of pain-related healthcare services among this group would be a useful next step.

Source: Jenna L. Adamowicz, Emily B. K. Thomas, Brian C. Lund, Mary A. Driscoll, Mark Vander Weg & Katherine Hadlandsmyth (2023) A population-based investigation into the prevalence of chronic fatigue syndrome in United States military Veterans with chronic pain, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2023.2239977

Consistency of inconsistency in long-COVID-19 pain symptoms persistency: A systematic review and meta-analysis

Abstract:

Introduction: Individuals recovering from acute COVID-19 episodes may continue to suffer from various ongoing symptoms, collectively referred to as Long-COVID. Long-term pain symptoms are amongst the most common and clinically significant symptoms to be reported for this post-COVID-19 syndrome.

Objectives: This systematic review and meta-analysis aimed to evaluate the proportions of persisting pain symptoms experienced by individuals past the acute phase of COVID-19 and to identify their associated functional consequences and inflammatory correlates.

Methods: Two online databases were systematically searched from their inception until 31 March 2022. We searched primary research articles in English, which evaluated individuals after laboratory-confirmed COVID-19 acute phase resolution and specifically reported on pain symptoms and their inflammatory and/or functional outcomes.

Results: Of the 611 identified articles, 26 were included, used for data extraction, and assessed for their methodological quality and risk of bias by two independent reviewers. Pain symptoms were grouped under one of six major pain domains, serving as our primary co-outcomes. Proportional meta-analyses of pooled logit-transformed values of single proportions were performed using the random-effects-restricted maximum-likelihood model. An estimated 8%, 6%, 18%, 18%, 17%, and 12% of individuals continued to report the persistence of chest, gastrointestinal, musculoskeletal joint, musculoskeletal muscle, general body, and nervous system-related pain symptoms, respectively, for up to one year after acute phase resolution of COVID-19. Considerable levels of heterogeneity were demonstrated across all results. Functional and quality-of-life impairments and some inflammatory biomarker elevations were associated with the persistence of long-COVID pain symptoms.

Conclusion: This study’s findings suggest that although not well characterized, long-COVID pain symptoms are being experienced by non-negligible proportions of those recovering from acute COVID-19 episodes, thus highlighting the importance of future research efforts to focus on this aspect.

Source: Kerzhner O, Berla E, Har-Even M, Ratmansky M, Goor-Aryeh I. Consistency of inconsistency in long-COVID-19 pain symptoms persistency: A systematic review and meta-analysis. Pain Pract. 2023 Jul 21. doi: 10.1111/papr.13277. Epub ahead of print. PMID: 37475709. https://onlinelibrary.wiley.com/doi/10.1111/papr.13277 (Full study)

Evidence of neuroinflammation in fibromyalgia syndrome: a [18F]DPA-714 positron emission tomography study

Abstract:

This observational study aimed to determine whether individuals with fibromyalgia (FM) exhibit higher levels of neuroinflammation than healthy controls (HCs), as measured with positron emission tomography using [18F]DPA-714, a second-generation radioligand for the translocator protein (TSPO).
Fifteen women with FM and 10 HCs underwent neuroimaging. Distribution volume (VT) was calculated for in 28 regions of interest (ROIs) using Logan graphical analysis and compared between groups using multiple linear regressions. Group (FM vs HC) was the main predictor of interest and TSPO binding status (high- vs mixed-affinity) was added as a covariate. The FM group had higher VT in the right postcentral gyrus (b = 0.477, P = 0.033), right occipital gray matter (GM; b = 0.438, P = 0.039), and the right temporal GM (b = 0.466, P = 0.042). The FM group also had lower VT than HCs in the left isthmus of the cingulate gyrus (b = −0.553, P = 0.014).
In the subgroup of high-affinity binders, the FM group had higher VT in the bilateral precuneus, postcentral gyrus, parietal GM, occipital GM, and supramarginal gyrus. Group differences in the right parietal GM were associated with decreased quality of life, higher pain severity and interference, and cognitive problems.
In support of our hypothesis, we found increased radioligand binding (VT) in the FM group compared with HCs in several brain regions regardless of participants’ TSPO binding status. The ROIs overlapped with prior reports of increased TSPO binding in FM. Overall, increasing evidence supports the hypothesis that FM involves microglia-mediated neuroinflammation in the brain.
Source: Mueller C, Fang YD, Jones C, McConathy JE, Raman F, Lapi SE, Younger JW. Evidence of neuroinflammation in fibromyalgia syndrome: a [18F]DPA-714 positron emission tomography study. Pain. 2023 Jun 15. doi: 10.1097/j.pain.0000000000002927. Epub ahead of print. PMID: 37326674. https://pubmed.ncbi.nlm.nih.gov/37326674/

Musculoskeletal involvement: COVID-19 and post COVID 19

Abstract:

The worldwide pandemic of coronavirus disease 2019 (COVID-19) was known to predominantly affect the lungs, but it was realized that COVID-19 had a large variety of clinical involvement. Cardiovascular, gastrointestinal, neurological, and musculoskeletal systems are involved by direct or indirect mechanisms with various manifestations.

The musculoskeletal involvement can manifest during COVID-19 infection, due to medications used for the treatment of COVID-19, and in the post/long COVID-19 syndrome. The major symptoms are fatigue, myalgia/arthralgia, back pain, low back pain, and chest pain. During the last two years, musculoskeletal involvement increased, but no clear consensus was obtained about the pathogenesis. However, there is valuable data that supports the hypothesis of angiotensinconverting enzyme 2, inflammation, hypoxia, and muscle catabolism. Additionally, medications that were used for treatment also have musculoskeletal adverse effects, such as corticosteroid-induced myopathy and osteoporosis. Therefore, while deciding the drugs, priorities and benefits should be taken into consideration.

Symptoms that begin three months from the onset of the COVID-19 infection, continue for at least two months, and cannot be explained by another diagnosis is accepted as post/long COVID-19 syndrome. Prior symptoms may persist and fluctuate, or new symptoms may manifest. In addition, there must be at least one symptom of infection. Most common musculoskeletal symptoms are myalgia, arthralgia, fatigue, back pain, muscle weakness, sarcopenia, impaired exercise capacity, and physical performance. In addition, the female sex, obesity, elderly patients, hospitalization, prolonged immobility, having mechanical ventilation, not having vaccination, and comorbid disorders can be accepted as clinical predictors for post/long COVID-19 syndrome.

Musculoskeletal pain is also a major problem and tends to be in chronic form. There is no consensus on the mechanism, but inflammation and angiotensin-converting enzyme 2 seem to play an important role. Localized and generalized pain may occur after COVID-19, and general pain is at least as common as localized pain. An accurate diagnosis allows physicians to initiate pain management and proper rehabilitation programs.

Source: Evcik D. Musculoskeletal involvement: COVID-19 and post COVID 19. Turk J Phys Med Rehabil. 2023 Feb 28;69(1):1-7. doi: 10.5606/tftrd.2023.12521. PMID: 37201006; PMCID: PMC10186015.

Fatigue in Children and Adolescents: A Population-Based Longitudinal Study on Fatigue and Chronic Pain

Abstract:

Objective: There are limited data on the prevalence and stability of fatigue in pediatrics, particularly among youth with chronic pain. Little is known about longitudinal effects of fatigue on health outcomes such as sleep quality, psychological distress, Health-Related Quality of Life, and chronic pain.

Methods: A community-based sample of N = 1276 students (9-17 years; 52% female; 30.3% with chronic pain) from 3 schools was screened at 2 measurement points 3 months apart. Prevalence and stability of fatigue were examined. Longitudinal analyses regarding fatigue and health outcomes were run using repeated measures correlations. The impact of change in fatigue on pain progression was analyzed using multilevel linear models.

Results: In the total community sample, 4.4% reported severe fatigue symptoms. The prevalence of severe fatigue was significantly higher in students with chronic pain (11.4%) compared to those without (1.3%). Fatigue symptoms persisted for several months, worsening of symptoms was more common and improvement less common in children with chronic pain. Sleep, psychological distress, and Health-Related Quality of Life were significantly associated with fatigue across both measurement points (rs = |0.16-0.44|), with no significant differences in the strength of correlations between children with and without chronic pain (ps > .05). There was a significant interaction between change in fatigue and courses of pain intensity and functional impairment.

Conclusions: Fatigue is highly prevalent, particularly in youth with chronic pain. The negative association of fatigue with health outcomes, and its impact on the course of pain, require early identification and treatment of those affected to prevent negative long-term consequences.

Source: Sommer A, Grothus S, Claus BB, Stahlschmidt L, Wager J. Fatigue in Children and Adolescents: A Population-Based Longitudinal Study on Fatigue and Chronic Pain. J Pediatr Psychol. 2023 May 10:jsad026. doi: 10.1093/jpepsy/jsad026. Epub ahead of print. PMID: 37164626. https://pubmed.ncbi.nlm.nih.gov/37164626/