Myalgia and Fatigue: Translation from Mouse Sensory Neurons to Fibromyalgia and Chronic Fatigue Syndromes

Excerpt:

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.

 

Source: Light AR, Vierck CJ, Light KC. Myalgia and Fatigue: Translation from Mouse Sensory Neurons to Fibromyalgia and Chronic Fatigue Syndromes. In: Kruger L, Light AR, editors. Translational Pain Research: From Mouse to Man. Boca Raton, FL: CRC Press/Taylor & Francis; 2010. Chapter 11. Frontiers in Neuroscience. https://www.ncbi.nlm.nih.gov/books/NBK57253/ (Full chapter)

 

The financial and psychological impacts on mothers of children with chronic fatigue syndrome (CFS/ME)

Abstract:

BACKGROUND: Paediatric chronic fatigue syndrome or myalgic encephalopathy (CFS/ME) is relatively common and children can be severely affected attending little or no school for extended periods. There are no studies quantifying the financial impact of having a child with CFS/ME and there is little information of the impact on parental mood.

METHODS: Forty mothers of children with CFS/ME from a regional specialist CFS/ME service completed inventories to assess their psychological well-being (Hospital Anxiety and Depression Scale, General Health Questionnaire-12) loss of earnings and increased expenditure. In addition, eight mothers took part in a semi-structured qualitative interview.

RESULTS: Most parents of children with CFS/ME experience loss of monthly income (mean = £247) and increase in monthly expenditure (mean = £206). Twenty-eight (72%) mothers were above the cut-off for the General Health Questionnaire-12 compared with 20% in the healthy population (95% CI 55, 85, P < 0.001) suggesting they probably have a mental health problem. This may be explained by the qualitative interviews where mothers described five areas contributing to poor parental health: lack of understanding from others; marital tension; concern about their child’s distress; concern about the impact on siblings and emotional distress causing physical symptoms.

CONCLUSIONS: The majority of families of children with CFS/ME experience decreased income and increased expenditure with a marked impact on maternal psychological health. Clinicians need to be aware of this to provide appropriate support to families who care for children with CFS/ME.

© 2011 Blackwell Publishing Ltd.

 

Source: Missen A, Hollingworth W, Eaton N, Crawley E. The financial and psychological impacts on mothers of children with chronic fatigue syndrome (CFS/ME). Child Care Health Dev. 2012 Jul;38(4):505-12. doi: 10.1111/j.1365-2214.2011.01298.x. Epub 2011 Sep 1. https://www.ncbi.nlm.nih.gov/pubmed/21880054

 

Small wins matter in advocacy movements: giving voice to patients

Abstract:

In this article, the various players are delineated in a story of a contested illness and patient advocacy, played out within the corridors of federal power. It is suggested that the mistreatment and negative attitudes that health care providers and others have towards those with chronic fatigue syndrome (CFS) is possibly due to the social construction of this illness as being a “Yuppie flu” disease. Institutional factors are identified that created these norms and attributions, as well as the multiple stakeholders and constituent groups invested in exerting pressure on policy makers to effect systemic change. This article also provides examples of how the field of Community Psychology, which is fundamentally committed to/based on listening to and giving voice to patients, is broadly relevant to patient activism communities. This approach focused, over time, on epidemiological studies, the name, the case definition, and ultimately the change in CFS leadership at the Centers for Disease Control and Prevention. Keys to this “small wins” approach were coalition building, use of “oppositional experts” (professionals in the scientific community who support patient advocacy goals) to challenge federal research, and taking advantage of developing events/shifts in power. Ultimately, this approach can result in significant scientific and policy gains, and changes in medical and public perception of an illness.

 

Source: Jason LA. Small wins matter in advocacy movements: giving voice to patients. Am J Community Psychol. 2012 Jun;49(3-4):307-16. doi: 10.1007/s10464-011-9457-7. https://www.ncbi.nlm.nih.gov/pubmed/21858612

 

Premorbid risk markers for chronic fatigue syndrome in the 1958 British birth cohort

Abstract:

BACKGROUND: Little is known about the aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME); prospective studies suggest a role for premorbid mood disorder.

AIMS: To examine childhood and early adult adversity, ill health and physical activity as premorbid risk markers for CFS/ME by 42 years, taking psychopathology into account.

METHOD: Data were from the 1958 British birth cohort, a prospective study from birth to 42 years (n = 11 419). The outcomes were self-reported CFS/ME (n = 127) and operationally defined CFS-like illness (n = 241) at 42 years.

RESULTS: Adjusting for psychopathology, parental physical abuse (odds ratio (OR) = 2.10, 95% CI 1.16-3.81), childhood gastrointestinal symptoms (OR = 1.58, 95% CI 1.00-2.50) and parental reports of many colds (OR = 1.65, 95% CI 1.09-2.50) were independently associated with self-reported CFS/ME. Female gender and premorbid psychopathology were the only risk markers for CFS-like illness, independent of comorbid psychopathology.

CONCLUSIONS: This confirms the importance of premorbid psychopathology in the aetiological pathways of CFS/ME, and replicates retrospective findings that childhood adversity may play a role in a minority.

Comment in: Childhood sexual abuse and chronic fatigue syndrome. [Br J Psychiatry. 2012]

 

Source: Clark C, Goodwin L, Stansfeld SA, Hotopf M, White PD. Premorbid risk markers for chronic fatigue syndrome in the 1958 British birth cohort. Br J Psychiatry. 2011 Oct;199(4):323-9. doi: 10.1192/bjp.bp.110.083956. Epub 2011 Aug 18. http://bjp.rcpsych.org/content/199/4/323.long (Full article)

 

Length of illness does not predict cognitive dysfunction in chronic fatigue syndrome

Abstract:

Neuropsychological studies have shown cognitive impairment in chronic fatigue syndrome (CFS), particularly in information-processing speed. The aim of this study was to examine the evolution of cognitive impairment in CFS. The evolution is one of the most disabling aspects of the CFS, and it has received little attention in the literature. Fifty-six women with CFS were assessed with neuropsychological tests. Patients were divided into three groups based on the duration of the disease. There were no differences between groups in terms of cognitive function. The cognitive impairment in CFS was not found to be more severe with longer disease duration. These data suggest that there is no progressive cognitive impairment in patients with CFS. Therefore, the cognitive deficits in CFS should be treated with cognitive rehabilitation programs focused on improving emotional distress associated to the illness and on promoting functional abilities.

 

Source: Santamarina-Perez P, Eiroa-Orosa FJ, Freniche V, Moreno-Mayos A, Alegre J, Saez N, Jacas C. Length of illness does not predict cognitive dysfunction in chronic fatigue syndrome. Appl Neuropsychol. 2011 Jul;18(3):216-22. Doi: 10.1080/09084282.2011.595448. https://www.ncbi.nlm.nih.gov/pubmed/21846221

 

Deviations in daily physical activity patterns in patients with the chronic fatigue syndrome: a case control study

Abstract:

OBJECTIVES: Deviations in daily physical activity patterns may play an important role in the development and maintenance of fatigue in the chronic fatigue syndrome (CFS). The aim of this study is to gain insight into the objective daily physical activity pattern of patients with CFS in comparison with healthy controls. The secondary objective is studying the awareness in performing physical activities.

METHODS: The objective daily physical activity pattern was measured with a tri-axial accelerometer in 35 patients with CFS and in 35 age- and gender-matched healthy controls. The objective daily physical activity level and distribution of physical activities at low, medium and high intensity levels during the day were measured. Moreover, variability in performing physical activities within and between subjects was computed. Subjective ratings of self-reported daily physical activity levels were assessed at a visual analog scale.

RESULTS: CFS patients were significantly less physically active in the afternoon and evening, and spent fewer activities at high intensity levels and more at low intensity levels. Moreover, CFS patients showed more variability in their own physical activity pattern during the afternoon. The heterogeneity in the physical activity pattern between subjects within the CFS and control group did not differ. Finally, CFS patients were more aware about their daily physical activity level than healthy controls.

CONCLUSION: CFS patients showed deviations in the objectively measured daily physical activity pattern. Future research should elucidate the relation between impaired balances in daily physical activity patterns and fatigue severity in CFS.

Copyright © 2011 Elsevier Inc. All rights reserved.

 

Source: Evering RM, Tönis TM, Vollenbroek-Hutten MM. Deviations in daily physical activity patterns in patients with the chronic fatigue syndrome: a case control study. J Psychosom Res. 2011 Sep;71(3):129-35. doi: 10.1016/j.jpsychores.2011.04.004. Epub 2011 May 18. https://www.ncbi.nlm.nih.gov/pubmed/21843746

 

Measuring disability in patients with chronic fatigue syndrome: reliability and validity of the Work and Social Adjustment Scale

Abstract:

BACKGROUND: Disability is a defining feature of chronic conditions, and it is an increasingly used measure of therapy effectiveness. The Work and Social Adjustment Scale (WSAS) is a simple and clear measure of disability. Although the scale is widely used, no study has yet investigated its psychometric properties in patients with chronic fatigue syndrome (CFS).

METHODS: Data from two samples of patients were used, one from a multicenter randomized controlled clinical trial of treatments for CFS (n =639) and the other from a clinic that specializes in CFS (n=384). All patients completed the WSAS as well as other measures.

RESULTS: Internal consistency and the Spearman-Brown split-half coefficient values indicated that the scale is reliable. CFS patients who had comorbid diagnoses of depression, anxiety or fibromyalgia had higher WSAS scores. High levels of disability were associated with high number of physical symptoms, severe fatigue, depression, anxiety, poor sleep quality and poor physical fitness, with correlation coefficients ranging between 0.41 and 0.11. Lower scores on the WSAS were modestly associated with better physical functioning as well as higher levels of physical capacity as assessed by a walking test. Sensitivity to change was evaluated in a subgroup of patients who had undergone a course of cognitive behavioral therapy. Disability significantly decreased after therapy and remained stable at follow-ups.

CONCLUSION: The WSAS is a reliable and valid assessment tool for disability in patients with CFS.

Copyright © 2011 Elsevier Inc. All rights reserved.

 

Source: Cella M, Sharpe M, Chalder T. Measuring disability in patients with chronic fatigue syndrome: reliability and validity of the Work and Social Adjustment Scale. J Psychosom Res. 2011 Sep;71(3):124-8. doi: 10.1016/j.jpsychores.2011.02.009. Epub 2011 Apr 3. https://www.ncbi.nlm.nih.gov/pubmed/21843745

 

Cumulative life stress in chronic fatigue syndrome

Abstract:

We studied the impact of cumulative life stress on CFS in a population-based study. We found that exposure to stressors was significantly more common in persons with CFS compared to NF controls; those with CFS reported experiencing significantly higher levels of psychological distress. Also, post-traumatic stress disorder was significantly more common in people with CFS. These results not only corroborate findings from other studies but, importantly, extend those by: a) measuring a comprehensive spectrum of stress variables, b) for the first time presenting data on stress in a population-based study, thus minimizing the effects of recruitment bias, and c) diagnosing CFS by means of standardized, validated scales, thus allowing replication and extension of our findings. Stress may be an important factor in the pathophysiology of CFS. Consequently, future studies should provide a more detailed understanding of the processes that lead from stress to CFS using longitudinal designs.

Published by Elsevier Ireland Ltd.

 

Source: Nater UM, Maloney E, Heim C, Reeves WC. Cumulative life stress in chronic fatigue syndrome. Psychiatry Res. 2011 Sep 30;189(2):318-20. doi: 10.1016/j.psychres.2011.07.015. Epub 2011 Aug 15. https://www.ncbi.nlm.nih.gov/pubmed/21840607

 

Does the heterogeneity of chronic fatigue syndrome moderate the response to cognitive behaviour therapy? An exploratory study

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a heterogeneous condition. A few studies have shown that some independent factors predict outcomes after cognitive behaviour therapy (CBT). Two recent systematic reviews suggest that heterogeneity may moderate treatment outcomes. However, no study has explored whether subgroups of CFS predict response to treatment.

METHODS: We used both latent class analysis (LCA) and latent class regression (LCR) to clarify the relationship between subgroups of CFS patients (n = 236), diagnosed using the Oxford diagnostic criteria, and the response to CBT. We measured symptoms, demographics, mood, and cognitive and behavioural responses to illness to define subgroups.

RESULTS: We found 5 latent classes by LCA, which did not differ in the direction of their response to CBT, with all classes showing improvement. In contrast, an exploratory LCR identified 4 latent classes, 1 of which predicted a poor response to CBT, whereas the other 3 predicted a good outcome, accounting for more than 70% of the patients. The negative outcome class was defined by weight fluctuations and physical shakiness, anxiety, pain and being focused on symptoms.

CONCLUSIONS: CBT should be offered to all classes of patients with CFS, when defined by these measures. It may be possible to predict a minority group with a negative outcome, but this exploratory work needs replication.

Copyright © 2011 S. Karger AG, Basel.

 

Source: Cella M, Chalder T, White PD. Does the heterogeneity of chronic fatigue syndrome moderate the response to cognitive behaviour therapy? An exploratory study. Psychother Psychosom. 2011;80(6):353-8. doi: 10.1159/000327582. Epub 2011 Aug 6. https://www.ncbi.nlm.nih.gov/pubmed/21829047

 

Data mining: comparing the empiric CFS to the Canadian ME/CFS case definition

Abstract:

This article contrasts two case definitions for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We compared the empiric CFS case definition (Reeves et al., 2005) and the Canadian ME/CFS clinical case definition (Carruthers et al., 2003) with a sample of individuals with CFS versus those without. Data mining with decision trees was used to identify the best items to identify patients with CFS. Data mining is a statistical technique that was used to help determine which of the survey questions were most effective for accurately classifying cases. The empiric criteria identified about 79% of patients with CFS and the Canadian criteria identified 87% of patients. Items identified by the Canadian criteria had more construct validity. The implications of these findings are discussed.

© 2011 Wiley Periodicals, Inc.

 

Source: Jason LA, Skendrovic B, Furst J, Brown A, Weng A, Bronikowski C. Data mining: comparing the empiric CFS to the Canadian ME/CFS case definition. J Clin Psychol. 2012 Jan;68(1):41-9. doi: 10.1002/jclp.20827. Epub 2011 Aug 5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228898/ (Full article)