Sykdommen Myagisk Encefalopati (ME) er ganske så sikkert den eneste tilstanden hvor pasienten ikke KAN trene seg friskere, ikke KAN oppnå økt kondis, ikke KAN svi av overvekt. Det er lettere å forklare eller tenke seg til om du selv trener. Normalt sier en at du skal ha en treningspuls på 220 minus alder, sånn cirka, ved max treningseffekt. Om du er på spinning roper instruktøren vel litt ofte om anaerobisk terskel (AT). Det er når muskelcellene dine går tom for djuus og organellen som er ansvarlig for produksjon av ATP i mitokondriene ikke får nok oksygen (som forøvrig er den eneste funksjonen til oksygen). Når muskelceller når AT produseres melkesyre istedet. (bare det tar fire ganger mer energi å bryte de ned).
Når max treningspuls til en som er rammet med ME er ett sted mellom 90 til 120 før AT inntreffer avhengig av faktoren tid og intensitet, står utfordringene om ett funksjonelt liv i kø!
Dette kjernesymptomet til sykdommen ME karakterieseres av akkurat det; mangel på produsert energi og det blir ikke bedre av at kroppen i tillegg har en selvmotsigende lav evne til restitusjon.
Forsker Katarina Lien sier blant annet dette i forskningsprotokollen «Nytten av gjentatt sykkelbelastning hos pasienter med ME/CFS»: Begrepet Post Exertional Malaise (PEM) brukes om den aktivitetsutløste forverringen og sykdomsfølelsen som ser ut til å skille ME/CFS fra andre kroniske utmattelsestilstander.
Årsaken til PEM er ukjent, og selv lett aktivitet kan føre til utmattelse og symptomforverring med forlenget restitusjonstid >24 timer. Det er vist at pasienter med ME/CFS har en endret genekspresjon etter 25 minutter med moderat fysisk aktivitet sammenliknet med friske, inaktive individer, med økt ekspresjon av sensoriske, adrenerge og immunologiske gener.
Denne endringen skjer umiddelbart, vedvarer i minst 2 døgn, og korrelerer med pasientens egenrapporterte symptomforverring (Light et al. 2009).
Ergospirometri måler fysisk prestasjonsevne, aerob kapasitet, ved hjelp av gradvis økende belastning på tredemølle eller sykkel til det maksimale av hva testpersonen kan klare.
Samtidig overvåkes hjertefrekvens, tidevolum, oksygenforbruk og CO2 produksjon. Ut fra dette beregnes VO2max, anaerob terskel, maksimalpuls, maksimal arbeidskapasitet og arbeidskapasitet ved anaerob terskel. Ergospirometri er en validert og mye brukt metode for å evaluere funksjonsnivået ved en rekke kroniske sykdommer. Funnene er objektive, reproduserbare og kan også gi informasjon om hvilke mekanismer som kan ligge til grunn for en eventuell begrensning.
Ergospirometri som mulig metode i diagnostikk av ME/CFS
De senere årene er det gjort flere studier der man anvender ergospirometri for å demonstrere den aktivitetsutløste forverringen (PEM) som ses ved ME/CFS. PEM ledsages av en markant reduksjon i maksimal arbeidskapasitet fra en dag til den neste. Dette er ikke kjent ved andre sykdommer og er dermed muligens en diagnostisk markør for ME/CFS. Pasienter med ME/CFS som testes med 24 timers mellomrom har en signifikant reduksjon i VO2max og anaerob terskel. Til sammenlikning har måling av VO2max hos friske og andre pasientgrupper en svært høy grad av reproduserbarhet over dager og måneder
Det har i lang tid vært etisk utfordrende at en gruppe pasienter opplever at de ikke tas på alvor og at det til stadighet synses rundt både årsak, diagnostisering og hva som er egnet behandling.
Pasienter med ME/CFS har blitt fortalt at de bare må ta seg sammen, slutte å være late, slutte å klage, og ønske å bli friske. De møter stadig utfordringer i forhold til skole, utdanning, arbeid, offentlige etater, samt mangel på helsetilbud og hjelpetiltak.
Mange oppfatter fremdeles ME/CFS som en psykosomatisk tilstand fremfor en sykdom med grunnlag i biologiske forandringer, dette gjelder både helsearbeidere og legfolk. Som følge av dette har ME/CFS pasienter i stor grad blitt overlatt til seg selv og det er ikke uvanlig at de har brukt store summer på privat og/eller alternativ behandling med manglende dokumentert effekt.
Vi kjenner til både leger og NAV-kontor som har krevd at pasienter deltar på, og selv betaler 15.000 kroner for, kurs i såkalt «Lightning Process». Dette er en udokumentert behandlingsform som har ført til betydelig og langvarig forverring hos flere. Det er heller ikke uvanlig med henvisning til kognitiv atferdsterapi, noe pasientene selv kan oppleve som en urimelig psykologisering av somatiske plager. Pasienter har også blitt tvunget til arbeidsutprøving med langvarig forverring som resultat.
Hva skjer når ME-pasienter trener eller har for høy aktivitet (kognitivt, såvel som fysisk)?
Nedenfor finner du en samling av publikasjoner som motbeviser den såkalte påstanden du ofte hører om at det er [dokumentert og evidensbasert kunnskap at kognitiv terapi, LP og treningsterapi ala GET er det som gjør ME-pasienter friske]. Denne påstanden har blitt systematisk indoktrinert siden slutten av 80-tallet ved bruk av brudd på en rekke etiske prinispper i forskningsmetode. Dette speiles seg i dag ved feks: oversiktsanalyser, bruk av sitater fra enkeltstudier, samt at forskningsråd og helsestyre i ulike land ikke tar ansvar for det som er synlig under «Flawed Science/research». Eksempler at at deltakere ble bedt å ignorere symptomer i forkant, «drop-ut» blir betegnet som latskap og motivasjonssvikt, samt trusler mot (og for noen er det en realitet) innleggelse i psykriatri og overtakelse av formynderansvar, samt andre ytelser.
Andre blogginnlegg som kan være relevant og nyttig lesning:
Relevante forskningspublikasjoner om ME og Trening
Phys Ther. 2013 Nov;93(11):1484-92. doi: 10.2522/ptj.20110368. Epub 2013 Jun 27.
Reduced functional capacity and postexertion fatigue after physical activity are hallmark symptoms of chronic fatigue syndrome (CFS) and may even qualify for biomarker status. That these symptoms are often delayed may explain the equivocal results for clinical cardiopulmonary exercise testing in people with CFS. Test reproducibility in people who are healthy is well documented. Test reproducibility may not be achievable in people with CFS because of delayed symptoms.
The objective of this study was to determine the discriminative validity of objective measurements obtained during cardiopulmonary exercise testing to distinguish participants with CFS from participants who did not have a disability but were sedentary.
A prospective cohort study was conducted.
Gas exchange data, workloads, and related physiological parameters were compared in 51 participants with CFS and 10 control participants, all women, for 2 maximal exercise tests separated by 24 hours.
Multivariate analysis showed no significant differences between control participants and participants with CFS for test 1. However, for test 2, participants with CFS achieved significantly lower values for oxygen consumption and workload at peak exercise and at the ventilatory or anaerobic threshold. Follow-up classification analysis differentiated between groups with an overall accuracy of 95.1%.
Only individuals with CFS who were able to undergo exercise testing were included in this study. Individuals who were unable to meet the criteria for maximal effort during both tests, were unable to complete the 2-day protocol, or displayed overt cardiovascular abnormalities were excluded from the analysis.
The lack of any significant differences between groups for the first exercise test would appear to support a deconditioning hypothesis for CFS symptoms. However, the results from the second test indicated the presence of CFS-related postexertion fatigue. It might be concluded that a single exercise test is insufficient to reliably demonstrate functional impairment in people with CFS. A second test might be necessary to document the atypical recovery response and protracted fatigue possibly unique to CFS, which can severely limit productivity in the home and workplace.
Disabil Rehabil. 2011;33(25-26):2596-604. doi: 10.3109/09638288.2011.582925. Epub 2011 Jun 20.
To determine the validity and reliability of Short Form 36 Version 2 (SF36v2) in sub-groups of individuals with fatigue.
Thirty subjects participated in this study, including n = 16 subjects who met case definition criteria for chronic fatigue syndrome (CFS) and n = 14 non-disabled sedentary matched control subjects. SF36v2 and Multidimensional Fatigue Inventory (MFI-20) were administered before two maximal cardiopulmonary exercise tests (CPETs) administered 24 h apart and an open-ended recovery questionnaire was administered 7 days after CPET challenge. The main outcome measures were self-reported time to recover to pre-challenge functional and symptom status, frequency of post-exertional symptoms and SF36v2 sub-scale scores.
Individuals with CFS demonstrated significantly lower SF36v2 and MFI-20 sub-scale scores prior to CPET. Between-group differences remained significant post-CPET, however, there were no significant group by test interaction effects. Subjects with CFS reported significantly more total symptoms (p < 0.001), as well as reports of fatigue (p < 0.001), neuroendocrine (p < 0.001), immune (p < 0.01), pain (p < 0.01) and sleep disturbance (p < 0.01) symptoms than control subjects as a result of CPET. Many symptom counts demonstrated significant relationships with SF36v2 sub-scale scores (p < 0.05). SF36v2 and MFI-20 sub-scale scores demonstrated significant correlations (p < 0.05). Various SF36v2 sub-scale scores demonstrated significant predictive validity to identify subjects who recovered from CPET challenge within 1 day and 7 days (p < 0.05). Potential floor effects were observed for both questionnaires for individuals with CFS.
Various sub-scales of SF36v2 demonstrated adequate reliability and validity for clinical and research applications. Adequacy of sensitivity to change of SF36v2 as a result of a fatiguing stressor should be the subject of additional study.
Disabil Rehabil. 2011;33(19-20):1768-75. doi: 10.3109/09638288.2010.546936. Epub 2011 Jan 6.
To determine the diagnostic accuracy for single symptoms and clusters of symptoms to distinguish between individuals with and without chronic fatigue syndrome (CFS).
A cohort study was conducted in an exercise physiology laboratory in an academic setting. Thirty subjects participated in this study (n = 16 individuals with CFS; n = 14 non-disabled sedentary matched control subjects). An open-ended symptom questionnaire was administered 1 week following the second of two maximal cardiopulmonary exercise tests administered 24 h apart.
Receiver operating characteristics (ROC) curve analysis was significant for failure to recover within 1 day (area under the curve = 0.864, 95% confidence interval [CI]: 0.706-1.00, p = 0.001) but not within 7 days. Clinimetric properties of failure to recover within 1 day to predict membership in the CFS cohort were sensitivity 0.80, specificity 0.93, positive predictive value 0.92, negative predictive value 0.81, positive likelihood ratio 11.4, and negative likelihood ratio 0.22. Fatigue demonstrated high sensitivity and modest specificity to distinguish between cohorts, while neuroendocrine dysfunction, immune dysfunction, pain, and sleep disturbance demonstrated high specificity and modest sensitivity. ROC analysis suggested cut-point of three associated symptoms (0.871, 95% CI: 0.717-1.00, p < 0.001). A significant binary logistic regression model (p < 0.001) revealed immune abnormalities, sleep disturbance and pain accurately classified 92% of individuals with CFS and 88% of control subjects.
A cluster of associated symptoms distinguishes between individuals with and without CFS. Fewer associated symptoms may be necessary to establish a diagnosis of CFS than currently described.
Phys Ther. 2010 Apr;90(4):602-14. doi: 10.2522/ptj.20090047. Epub 2010 Feb 25.
Fatigue is one of the most common reasons why people consult health care providers. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is one cause of clinically debilitating fatigue. The underdiagnosis of CFS/ME, along with the spectrum of symptoms that represent multiple reasons for entry into physical therapy settings, places physical therapists in a unique position to identify this health condition and direct its appropriate management. The diagnosis and clinical correlates of CFS/ME are becoming better understood, although the optimal clinical management of this condition remains controversial. The 4 aims of this perspective article are: (1) to summarize the diagnosis of CFS/ME with the goal of promoting the optimal recognition of this condition by physical therapists; (2) to discuss aerobic system and cognitive deficits that may lead to the clinical presentation of CFS/ME; (3) to review the evidence for graded exercise with the goal of addressing limitations in body structures and functions, activity, and participation in people with CFS/ME; and (4) to present a conceptual model for the clinical management of CFS/ME by physical therapists.
J Womens Health (Larchmt). 2010 Feb;19(2):239-44. doi: 10.1089/jwh.2009.1507.
Postexertional malaise (PEM) is a defining characteristic of chronic fatigue syndrome (CFS) that remains a source of some controversy. The purpose of this study was to explore the effects of an exercise challenge on CFS symptoms from a patient perspective.
This study included 25 female CFS patients and 23 age-matched sedentary controls. All participants underwent a maximal cardiopulmonary exercise test. Subjects completed a health and well-being survey (SF-36) 7 days postexercise. Subjects also provided, approximately 7 days after testing, written answers to open-ended questions pertaining to physical and cognitive responses to the test and length of recovery. SF-36 data were compared using multivariate analyses. Written questionnaire responses were used to determine recovery time as well as number and type of symptoms experienced.
Written questionnaires revealed that within 24 hours of the test, 85% of controls indicated full recovery, in contrast to 0 CFS patients. The remaining 15% of controls recovered within 48 hours of the test. In contrast, only 1 CFS patient recovered within 48 hours. Symptoms reported after the exercise test included fatigue, light-headedness, muscular/joint pain, cognitive dysfunction, headache, nausea, physical weakness, trembling/instability, insomnia, and sore throat/glands. A significant multivariate effect for the SF-36 responses (p < 0.001) indicated lower functioning among the CFS patients, which was most pronounced for items measuring physiological function.
The results of this study suggest that PEM is both a real and an incapacitating condition for women with CFS and that their responses to exercise are distinctively different from those of sedentary controls.
In Vivo. 2005 Mar-Apr;19(2):387-90.
Hyperactivition of an unwanted cellular cascade by the immune-related protein RNase L has been linked to reduced exercise capacity in persons with chronic fatigue syndrome (CFS). This investigation compares exercise capacities of CFS patients with deregulation of the RNase L pathway and CFS patients with normal regulation, while controlling for potentially confounding gender effects. Thirty-five male and seventy-one female CFS patients performed graded exercise tests to voluntary exhaustion. Measures of peak VO2, peak heart rate, body mass index, perceived exertion, and respiratory quotient were entered into a two-way factorial analysis with gender and immune status as independent variables. A significant multivariate main effect was found for immune status (p < 0.01), with no gender effect or interaction. Follow-up analyses identified VO2(peak) as contributing most to the difference. These results implicate abnormal immune activity in the pathology of exercise intolerance in CFS and are consistent with a channelopathy involving oxidative stress and nitric oxide-related toxicity.
Immunologic aspects of chronic fatigue syndrome. Report on a Research Symposium convened by The CFIDS Association of America and co-sponsored by the US Centers for Disease Control and Prevention and the National Institutes of Health.
Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800,000 Americans of all ages, races, socioeconomic groups and genders. The etiology and pathophysiology of CFS are unknown, yet studies have suggested an involvement of the immune system.
A symposium was organized in October 2001 to explore the possibility of an association between immune dysfunction and CFS, with special emphasis on the interactions between immune dysfunction and other abnormalities noted in the neuroendocrine and autonomic nervous systems of individuals with CFS.
This paper represents the consensus of the panel of experts who participated in this meeting. Data suggest that persons with CFS manifest changes in immune responses that fall outside normative ranges, but current research does not provide definitive evidence on whether these immune abnormalities are a cause or result of the illness. It has become clear that CFS cannot be understood based on single measurements of immune, endocrine, cardiovascular, or autonomic nervous system dysfunction. This panel encourages a new emphasis on multidisciplinary research into CFS.
Med Sci Sports Exerc. 2003 Jun;35(6):908-13.
The purpose of this study was to examine physiological responses of persons with chronic fatigue syndrome (CFS) to a graded exercise test.
Cardiopulmonary exercise tests were performed on 189 patients diagnosed with CFS. Based on values for peak oxygen consumption, patients were assigned to one of four impairment categories (none, mild, moderate, and severe), using American Medical Association (AMA) guidelines. A one-way MANOVA was used to determine differences between impairment categories for the dependent variables of age, body mass index, percentage of predicted [OV0312]O(2), resting and peak heart rates, resting and peak systolic blood pressure, respiratory quotient (RQ), and rating of perceived exertion.
Significant differences were found between each impairment level for percentage of predicted [OV0312]O(2) and peak heart rate. Peak systolic blood pressure values for the «moderate,» and «severe» groups differed significantly from each other and both other groups. The more impaired groups had lower values. The no impairment group had a significantly higher peak RQ than each of the other impairment levels (all P < 0.001). Peak [OV0312]O(2) values were less than predicted for all groups. Compared with the males, the women achieved actual values for peak [OV0312]O(2) that were closer to their predicted values.
Despite a common diagnosis, the functional capacity of CFS patients varies greatly. Stratifying patients by function allows for a more meaningful interpretation of the responses to exercise and may enable differential diagnosis between subsets of CFS patients.
- Physiological factors limiting exercise performance in CFS. [Med Sci Sports Exerc. 2004]
In Vivo. 2002 Mar-Apr;16(2):107-9.
The elevated RNase L enzyme activity observed in some Chronic Fatigue Syndrome (CFS) patients may be linked to the low exercise tolerance and functional impairment that typify this disease.
The purpose of this investigation was to determine if specific indicators of physical performance can predict abnormal RNase L activity in CFS patients.
Seventy-three CFS patients performed a graded exercise test to voluntary exhaustion. Forty-six patients had elevated RNase L levels. This measure was employed as the dependent variable in a discriminant function analysis, with peak V02, exercise duration and Karnofsky Performance Scores (KPS) serving as the independent variables. All three variables entered the single significant function (p < 0.001).
The elevated RNase L group had a lower peak V02 and duration than the normal group, but a higher KPS. The results suggest that both exercise testing and the RNase L biomarker have potential to aid in the diagnosis of CFS.
PMID:12073768 [PubMed – indexed for MEDLINE]
Exp Physiol. 2014 Feb;99(2):368-80. doi: 10.1113/expphysiol.2013.075812. Epub 2013 Oct 18.
- Exp Physiol. 2014 Apr;99(4):740. White, Andrea T [added].
What is the central question of this study? Can physiological concentrations of metabolite combinations evoke sensations of fatigue and pain when injected into skeletal muscle?
If so, what sensations are evoked? What is the main finding and its importance?
Low concentrations of protons, lactate and ATP evoked sensations related to fatigue. Higher concentrations of these metabolites evoked pain. Single metabolites evoked no sensations. This suggests that the combination of an ASIC receptor and a purinergic P2X receptor is required for signalling fatigue and pain.
The results also suggest that two types of sensory neurons encode metabolites; one detects low concentrations of metabolites and signals sensations of fatigue, whereas the other detects higher levels of metabolites and signals ache and hot.
The perception of fatigue is common in many disease states; however, the mechanisms of sensory muscle fatigue are not understood. In mice, rats and cats, muscle afferents signal metabolite production in skeletal muscle using a complex of ASIC, P2X and TRPV1 receptors.
Endogenous muscle agonists for these receptors are combinations of protons, lactate and ATP. Here we applied physiological concentrations of these agonists to muscle interstitium in human subjects to determine whether this combination could activate sensations and, if so, to determine how the subjects described these sensations.
Ten volunteers received infusions (0.2 ml over 30 s) containing protons, lactate and ATP under the fascia of a thumb muscle, abductor pollicis brevis. Infusion of individual metabolites at maximal amounts evoked no fatigue or pain. Metabolite combinations found in resting muscles (pH 7.4 + 300 nm ATP + 1 mm lactate) also evoked no sensation. The infusion of a metabolite combination found in muscle during moderate endurance exercise (pH 7.3 + 400 nm ATP + 5 mm lactate) produced significant fatigue sensations. Infusion of a metabolite combination associated with vigorous exercise (pH 7.2 + 500 nm ATP + 10 mm lactate) produced stronger sensations of fatigue and some ache.
Higher levels of metabolites (as found with ischaemic exercise) caused more ache but no additional fatigue sensation. Thus, in a dose-dependent manner, intramuscular infusion of combinations of protons, lactate and ATP leads to fatigue sensation and eventually pain, probably through activation of ASIC, P2X and TRPV1 receptors.
This is the first demonstration in humans that metabolites normally produced by exercise act in combination to activate sensory neurons that signal sensations of fatigue and muscle pain.
- No pain, no gain: somatosensation from skeletal muscle. [Exp Physiol. 2014]
- Feedback from group III/IV muscle afferents is not the sensory signal for perception of effort. [Exp Physiol. 2014]
- Reply: To PMID 24142455. [Exp Physiol. 2014]
Psychoneuroendocrinology. 2013 Dec;38(12):2983-95. doi: 10.1016/j.psyneuen.2013.08.008. Epub 2013 Sep 6.
Androgen deprivation therapy (ADT) often worsens fatigue in patients with prostate cancer, producing symptoms similar to chronic fatigue syndrome (CFS). Comparing expression (mRNA) of many fatigue-related genes in patients with ADT-treated prostate cancer versus with CFS versus healthy controls, and correlating mRNA with fatigue severity may clarify the differing pathways underlying fatigue in these conditions.
Quantitative real-time PCR was performed on leukocytes from 30 fatigued, ADT-treated prostate cancer patients (PCF), 39 patients with CFS and 22 controls aged 40-79, together with ratings of fatigue and pain severity. 46 genes from these pathways were included: (1) adrenergic/monoamine/neuropeptides, (2) immune, (3) metabolite-detecting, (4) mitochondrial/energy, (5) transcription factors.
PCF patients showed higher expression than controls or CFS of 2 immune transcription genes (NR3C1 and TLR4), chemokine CXCR4, and mitochondrial gene SOD2. They showed lower expression of 2 vasodilation-related genes (ADRB2 and VIPR2), 2 cytokines (TNF and LTA), and 2 metabolite-detecting receptors (ASIC3 and P2RX7). CFS patients showed higher P2RX7 and lower HSPA2 versus controls and PCF. Correlations with fatigue severity were similar in PCF and CFS for only DBI, the GABA-A receptor modulator (r=-0.50, p<0.005 and r=-0.34, p<0.05). Purinergic P2RY1 was correlated only with PCF fatigue and pain severity (r=+0.43 and +0.59, p=0.025 and p=0.001).
PCF patients differed from controls and CFS in mean expression of 10 genes from all 5 pathways. Correlations with fatigue severity implicated DBI for both patient groups and P2RY1 for PCF only. These pathways may provide new targets for interventions to reduce fatigue.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Chronic fatigue syndrome; Cytokine; Fatigue; GABA-receptor modulator; Gene expression; Prostate cancer; Purinergic; qPCR
J Intern Med. 2012 Jan;271(1):64-81. doi: 10.1111/j.1365-2796.2011.02405.x. Epub 2011 Jul 13.
To determine mRNA expression differences in genes involved in signalling and modulating sensory fatigue, and muscle pain in patients with chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FM) at baseline, and following moderate exercise.
Forty-eight patients with CFS only, or CFS with comorbid FM, 18 patients with FM that did not meet criteria for CFS, and 49 healthy controls underwent moderate exercise (25 min at 70% maximum age-predicted heart rate). Visual-analogue measures of fatigue and pain were taken before, during and after exercise. Blood samples were taken before and 0.5, 8, 24 and 48 h after exercise. Leucocytes were immediately isolated from blood, number coded for blind processing and analyses and flash frozen. Using real-time, quantitative PCR, the amount of mRNA for 13 genes (relative to control genes) involved in sensory, adrenergic and immune functions was compared between groups at baseline and following exercise. Changes in amounts of mRNA were correlated with behavioural measures and functional clinical assessments.
No gene expression changes occurred following exercise in controls. In 71% of patients with CFS, moderate exercise increased most sensory and adrenergic receptor’s and one cytokine gene’s transcription for 48 h. These postexercise increases correlated with behavioural measures of fatigue and pain. In contrast, for the other 29% of patients with CFS, adrenergic α-2A receptor’s transcription was decreased at all time-points after exercise; other genes were not altered. History of orthostatic intolerance was significantly more common in the α-2A decrease subgroup. FM-only patients showed no postexercise alterations in gene expression, but their pre-exercise baseline mRNA for two sensory ion channels and one cytokine were significantly higher than controls.
At least two subgroups of patients with CFS can be identified by gene expression changes following exercise. The larger subgroup showed increases in mRNA for sensory and adrenergic receptors and a cytokine. The smaller subgroup contained most of the patients with CFS with orthostatic intolerance, showed no postexercise increases in any gene and was defined by decreases in mRNA for α-2A. FM-only patients can be identified by baseline increases in three genes. Postexercise increases for four genes meet published criteria as an objective biomarker for CFS and could be useful in guiding treatment selection for different subgroups.
Pain Res Treat. 2012;2012:427869. doi: 10.1155/2012/427869. Epub 2011 Sep 29.
In complex multisymptom disorders like fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS) that are defined primarily by subjective symptoms, genetic and gene expression profiles can provide very useful objective information.
This paper summarizes research on genes that may be linked to increased susceptibility in developing and maintaining these disorders, and research on resting and stressor-evoked changes in leukocyte gene expression, highlighting physiological pathways linked to stress and distress. These include the adrenergic nervous system, the hypothalamic-pituitary-adrenal axis and serotonergic pathways, and exercise responsive metabolite-detecting ion channels.
The findings to date provide some support for both inherited susceptibility and/or physiological dysregulation in all three systems, particularly for catechol-O-methyl transferase (COMT) genes, the glucocorticoid and the related mineralocorticoid receptors (NR3C1, NR3C2), and the purinergic 2X4 (P2X4) ion channel involved as a sensory receptor for muscle pain and fatigue and also in upregulation of spinal microglia in chronic pain models.
Methodological concerns for future research, including potential influences of comorbid clinical depression and antidepressants and other medications, on gene expression are also addressed.
Psychosom Med. 2012 Jan;74(1):46-54. doi: 10.1097/PSY.0b013e31824152ed. Epub 2011 Dec 30.
Chronic fatigue syndrome (CFS) and multiple sclerosis (MS) are characterized by debilitating fatigue, yet evaluation of this symptom is subjective. We examined metabolite-detecting, adrenergic, and immune gene expression (messenger ribonucleic acid [mRNA]) in patients with CFS (n = 22) versus patients with MS (n = 20) versus healthy controls (n = 23) and determined their relationship to fatigue and pain before and after exercise.
Blood samples and fatigue and pain ratings were obtained at baseline and 0.5, 8, 24, and 48 hours after sustained moderate exercise. Leukocyte mRNA of four metabolite-detecting receptors (acid-sensing ion channel 3, purinergic type 2X4 and 2X5 receptors, and transient receptor potential vanilloid type 1) and four adrenergic (α-2a, β-1, and β-2 receptors and catechol-O-methyltransferase) and five immune markers (CD14, toll-like receptor 4 [TLR4], interleukin [IL] 6, IL-10, and lymphotoxin α) was examined using quantitative polymerase chain reaction.
Patients with CFS had greater postexercise increases in fatigue and pain (10-29 points above baseline, p < .001) and greater mRNA increases in purinergic type 2X4 receptor, transient receptor potential vanilloid type 1, CD14, and all adrenergic receptors than controls (mean ± standard error = 1.3 ± 0.14- to 3.4 ± 0.90-fold increase above baseline, p = .04-.005). Patients with CFS with comorbid fibromyalgia (n = 18) also showed greater increases in acid-sensing ion channel 3 and purinergic type 2X5 receptors (p < .05). Patients with MS had greater postexercise increases than controls in β-1 and β-2 adrenergic receptor expressions (1.4 ± 0.27- and 1.3 ± 0.06-fold increases, respectively, p = .02 and p < .001) and greater decreases in TLR4 (p = .02). In MS, IL-10 and TLR4 decreases correlated with higher fatigue scores.
Postexercise mRNA increases in metabolite-detecting receptors were unique to patients with CFS, whereas both patients with MS and patients with CFS showed abnormal increases in adrenergic receptors. Among patients with MS, greater fatigue was correlated with blunted immune marker expression.
J Intern Med. 2011 Oct;270(4):327-38. doi: 10.1111/j.1365-2796.2011.02428.x. Epub 2011 Aug 22.
Carruthers BM1, van de Sande MI, De Meirleir KL, Klimas NG, Broderick G, Mitchell T, Staines D, Powles AC, Speight N, Vallings R, Bateman L, Baumgarten-Austrheim B, Bell DS, Carlo-Stella N, Chia J, Darragh A, Jo D, Lewis D, Light AR, Marshall-Gradisbik S, Mena I, Mikovits JA, Miwa K, Murovska M, Pall ML, Stevens S.
The label ‘chronic fatigue syndrome’ (CFS) has persisted for many years because of the lack of knowledge of the aetiological agents and the disease process.
In view of more recent research and clinical experience that strongly point to widespread inflammation and multisystemic neuropathology, it is more appropriate and correct to use the term ‘myalgic encephalomyelitis’ (ME) because it indicates an underlying pathophysiology.
It is also consistent with the neurological classification of ME in the World Health Organization’s International Classification of Diseases (ICD G93.3). Consequently, an International Consensus Panel consisting of clinicians, researchers, teaching faculty and an independent patient advocate was formed with the purpose of developing criteria based on current knowledge.
Thirteen countries and a wide range of specialties were represented. Collectively, members have approximately 400 years of both clinical and teaching experience, authored hundreds of peer-reviewed publications, diagnosed or treated approximately 50 000 patients with ME, and several members coauthored previous criteria.
The expertise and experience of the panel members as well as PubMed and other medical sources were utilized in a progression of suggestions/drafts/reviews/revisions. The authors, free of any sponsoring organization, achieved 100% consensus through a Delphi-type process. The scope of this paper is limited to criteria of ME and their application.
Accordingly, the criteria reflect the complex symptomatology. Operational notes enhance clarity and specificity by providing guidance in the expression and interpretation of symptoms. Clinical and research application guidelines promote optimal recognition of ME by primary physicians and other healthcare providers, improve the consistency of diagnoses in adult and paediatric patients internationally and facilitate clearer identification of patients for research studies.
© 2011 The Association for the Publication of the Journal of Internal Medicine.
Psychophysiology. 2010 Jul 1;47(4):615-24. doi: 10.1111/j.1469-8986.2010.00978.x. Epub 2010 Mar 4.
Chronic fatigue syndrome (CFS) patients often report symptom flare (SF) for >24 h after moderate exercise (post-ex). We hypothesized that SF is linked to increases in circulating cytokines and CD40 Ligand (CD40L).
In 19 CFS patients and 17 controls, mental and physical fatigue and pain symptom ratings were obtained together with serum for 11 cytokines and CD40L before and at 0.5, 8, 24, and 48 h post-ex.
Before exercise, CFS had lower CD40L (p<.05) but similar cytokines versus controls. In subgroups based on SF at 48 h, high SF patients (n=11) increased in IL-1beta, IL-12, IL-6, IL-8, IL-10, and IL-13 (p<.05) 8 h post-ex. Low SF patients (n=8) showed post-ex decreases in IL-10, IL-13, and CD40L, and controls decreased in IL-10, CD40L, and TNFalpha (p<.05). Thus, in CFS, cytokine activity may vary directly with SF, which may explain prior inconsistent findings.
Translational Pain Research: From Mouse to Man. Boca Raton, FL: CRC Press; 2010. Chapter 11.
Frontiers in Neuroscience.
Muscle fatigue and pain are among the most common complaints at emergency rooms and clinics across the country. Fatigue and pain are often acute, remitting spontaneously or appearing to be attenuated by a variety of drugs and treatment modalities. In spite of these remissions, popular magazines (e.g., Time) estimate that each year Americans spend over $30 billion on herbal remedies and $50 billion on alternative therapies to treat symptoms that include muscle pain and fatigue. These statistics indicate that even acute muscle pain and fatigue are serious health problems that are not adequately addressed by current medical practice.
Occasionally, muscle pain and fatigue take on a chronic nature, leading to syndromes including chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS)—devastating conditions characterized by continuing, debilitating fatigue, which is made worse by even mild exercise in the case of CFS and by chronic widespread pain (CWP) with a particular emphasis in the muscles, which can prevent most or all activities in the case of FMS. Both of these conditions are frequently associated with each other and with a variety of other illnesses, such as temporomandibular disorder (TMD), irritable bowel syndrome (IBS), and multiple chemical sensitivity. These syndromes destroy lives, respond poorly to current treatment strategies, and can lead to exhaustion of the financial resources of afflicted patients. Together, these disorders affect 7 to 20 million people in the United States each year, as reported by various authorities (Reeves et al. 2007).
Clearly, patients with these syndromes deserve a concerted research effort to understand, treat, and eventually cure these illnesses. In contrast to cutaneous pain, which has been thoroughly studied and is comparatively well understood, the molecular mechanisms for muscle pain are still unknown. Even more enigmatic is the symptom of debilitating fatigue.
Mosso, in his compendious volume on the subject a century ago, remarked that all cultures seem to have just one word for fatigue (Mosso 1904). Yet fatigue describes many conditions, including failure of muscle fibers to shorten normally, deficient motor command signals, feelings of tiredness, heaviness, pressure, and weakness from muscles, and a feeling of mental fatigue that impedes concentration and performance of conceptual tasks. The subject of most physiological investigations of fatigue has been voluntary muscle contraction. Decreased function causing failure of voluntary muscle contraction can occur at all levels of the neuromuscular system, including the motor cortex, signaling to motoneurons, motoneuron signals to the muscle, excitation-contraction coupling in the muscle, and actin-myosin filament interactions. However, the most common failure is a decrease in the motor command signal from the motor cortex (see recent reports and reviews by Bellinger et al. 2008; Gibson et al. 2003; Noakes et al. 2005; St Clair and Noakes 2004). A recent review suggests that failures in voluntary muscle contraction are most often caused by a central comparator that integrates homeostatic inputs from many physiological systems and shuts down motor commands when energy resources are threatened (Noakes 2007). One of the homeostatic inputs is suggested to “originate from a difference between subconscious representations of baseline physiological homeostatic state and the state of physiological activity induced by physical activity, which creates a second order representation which is perceived by consciousnessproducing structures as the sensation of fatigue” (Gibson et al. 2003, page 174).
We suggest that there is a simpler sensation of fatigue that is triggered by inputs from specific receptors that are sensitive to metabolites produced by muscle contraction. We further propose that this elementary sensation is transduced, conducted, and perceived within a unique sensory system with properties analogous to other sensory modalities such as pain. We call it the “sensation of muscle fatigue.”
Copyright © 2010 by Taylor and Francis Group, LLC.
- 11.1. INTRODUCTION
- 11.2. DO SKELETAL MUSCLES HAVE TWO UNIQUE TYPES OF SENSORY RECEPTORS THAT DETECT METABOLITES: ONE TYPE NOCICEPTIVE (CAPABLE OF SIGNALING PAIN), THE OTHER ERGORECEPTIVE (CAPABLE OF DETECTING MUSCLE WORK)?
- 11.3. MOLECULAR RECEPTORS THAT ARE ACTIVATED BY METABOLITES PRODUCED BY MUSCLE CONTRACTION
- 11.4. THE NEED FOR TRANSLATIONAL BRIDGES TO FIBROMYALGIA AND CHRONIC FATIGUE SYNDROME
- 11.5. ARE THESE MOLECULAR RECEPTORS RESPONSIBLE FOR SENSORY MUSCLE FATIGUE AND MUSCLE PAIN?
- 11.6. TRANSLATION FROM MOUSE TO HUMAN
- 11.7. MOLECULAR RECEPTORS INVOLVED IN CHRONIC FATIGUE SYNDROME
- 11.8. DYSREGULATED MRNAS MAY ALSO EXPLAIN COMMON CO-MORBIDITIES OF CFS
- 11.9. CAN ACUTE FATIGUE LEAD TO CHRONIC FATIGUE?
- 11.10. COMMON CAUSES OF ACUTE FATIGUE MIGHT CAUSE UP-REGULATION OF THE mRNA FOR THE MOLECULAR RECEPTORS SUGGESTED TO MEDIATE SENSORY MUSCLE FATIGUE AND PAIN
- 11.11. MENTAL FATIGUE
- 11.12. SYMPATHETIC DYSREGULATION CONTRIBUTES TO ENHANCED SENSORY FATIGUE
- 11.13. ADRENERGIC RECEPTORS ON SENSORY NEURONS?
- 11.14. BACK TO THE MOUSE TO FIGURE OUT HOW ADRENERGIC RECEPTORS COULD INCREASE MUSCLE PAIN AND FATIGUE
- 11.15. FUTURE RESEARCH DIRECTIONS
J Pain. 2009 Oct;10(10):1099-112. doi: 10.1016/j.jpain.2009.06.003. Epub 2009 Jul 31.
Chronic fatigue syndrome (CFS) is characterized by debilitating fatigue, often accompanied by widespread muscle pain that meets criteria for fibromyalgia syndrome (FMS). Symptoms become markedly worse after exercise.
Previous studies implicated dysregulation of the sympathetic nervous system (SNS), and immune system (IS) in CFS and FMS.
We recently demonstrated that acid sensing ion channel (probably ASIC3), purinergic type 2X receptors (probably P2X4 and P2X5) and the transient receptor potential vanilloid type 1 (TRPV1) are molecular receptors in mouse sensory neurons detecting metabolites that cause acute muscle pain and possibly muscle fatigue. These molecular receptors are found on human leukocytes along with SNS and IS genes.
Real-time, quantitative PCR showed that 19 CFS patients had lower expression of beta-2 adrenergic receptors but otherwise did not differ from 16 control subjects before exercise. After a sustained moderate exercise test, CFS patients showed greater increases than control subjects in gene expression for metabolite detecting receptors ASIC3, P2X4, and P2X5, for SNS receptors alpha-2A, beta-1, beta-2, and COMT and IS genes for IL10 and TLR4 lasting from 0.5 to 48 hours (P < .05). These increases were also seen in the CFS subgroup with comorbid FMS and were highly correlated with symptoms of physical fatigue, mental fatigue, and pain.
These new findings suggest dysregulation of metabolite detecting receptors as well as SNS and IS in CFS and CFS-FMS.
Muscle fatigue and pain are major symptoms of CFS. After moderate exercise, CFS and CFS-FMS patients show enhanced gene expression for receptors detecting muscle metabolites and for SNS and IS, which correlate with these symptoms. These findings suggest possible new causes, points for intervention, and objective biomarkers for these disorders.
Exerc Immunol Rev. 2014;20:94-116.
Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review.
An increasing number of studies have examined how the immune system of patients with Chronic Fatigue Syndrome (CFS), or myalgic encephalomyelitis, responds to exercise.
The objective of the present study was to systematically review the scientific literature addressing exercise-induced immunological changes in CFS patients compared to healthy control subjects.
A systematic literature search was conducted in the PubMed and Web of science databases using different keyword combinations. We included 23 case control studies that examined whether CFS patients, compared to healthy sedentary controls, have a different immune response to exercise.
The included articles were evaluated on their methodological quality. Compared to the normal response of the immune system to exercise as seen in healthy subjects, patients with CFS have a more pronounced response in the complement system (i.e. C4a split product levels), oxidative stress system (i.e. enhanced oxidative stress combined with a delayed and reduced anti-oxidant response), and an alteration in the immune cells’ gene expression profile (increases in post-exercise interleukin-10 and toll-like receptor 4 gene expression), but not in circulating pro- or anti-inflammatory cytokines.
Many of these immune changes relate to post-exertional malaise in CFS, a major characteristic of the illness. The literature review provides level B evidence for an altered immune response to exercise in patients with CFS.
Free full text http://www.ncbi.nlm.nih.gov/pubmed/24974723
Dette var en rekke forskningsstudier og publikasjoner som ignoreres eller bortforklares i forskningslittereatur som omhandler ME og trening, ME og aktivitet, ME og kognitiv behandlingsterapi med eksponeringsøvelser, ME og faktorer som fysisk påvirker immunsystem, hormonsystem og nervessytem.
Der eksisterer forklaringer som at dine tanker og følelser har så stor kontroll over kroppens systemer, at det gjør deg syk. Selv om du er bevisst dine tanker og følelser, så er det de ubevisste tanker og følelser som styrer de biokjemiske prosessene, genene dine og det minste lille protein. Du har observert og lært det (innlært adferd).
Tror virkelig folk at tanker og følelser gjør deg syk – sykere enn stadum fire kreft (funksjonsnivå til minst 25 % – 60% av ME-pasientene)?
Kortlenke til dette blogginnlegget er: http://wp.me/p1wvHk-1tz