Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome

Abstract:

In addition to the debilitating fatigue, the majority of patients with chronic fatigue syndrome (CFS) experience chronic widespread pain. These pain complaints show the greatest overlap between CFS and fibromyalgia (FM). Although the literature provides evidence for central sensitization as cause for the musculoskeletal pain in FM, in CFS this evidence is currently lacking, despite the observed similarities in both diseases. The knowledge concerning the physiological mechanism of central sensitization, the pathophysiology and the pain processing in FM, and the knowledge on the pathophysiology of CFS lead to the hypothesis that central sensitization is also responsible for the sustaining pain complaints in CFS.

This hypothesis is based on the hyperalgesia and allodynia reported in CFS, on the elevated concentrations of nitric oxide presented in the blood of CFS patients, on the typical personality styles seen in CFS and on the brain abnormalities shown on brain images. To examine the present hypothesis more research is required. Further investigations could use similar protocols to those already used in studies on pain in FM like, for example, studies on temporal summation, spatial summation, the role of psychosocial aspects in chronic pain, etc.

 

Source: Meeus M, Nijs J. Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome. Clin Rheumatol. 2007 Apr;26(4):465-73. Epub 2006 Nov 18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1820749/ (Full article)

 

Sleep characteristics of persons with chronic fatigue syndrome and non-fatigued controls: results from a population-based study

Abstract:

BACKGROUND: The etiology and pathophysiology of chronic fatigue syndrome (CFS) remain inchoate. Attempts to elucidate the pathophysiology must consider sleep physiology, as unrefreshing sleep is the most commonly reported of the 8 case-defining symptoms of CFS. Although published studies have consistently reported inefficient sleep and documented a variable occurrence of previously undiagnosed primary sleep disorders, they have not identified characteristic disturbances in sleep architecture or a distinctive pattern of polysomnographic abnormalities associated with CFS.

METHODS: This study recruited CFS cases and non-fatigued controls from a population based study of CFS in Wichita, Kansas. Participants spent two nights in the research unit of a local hospital and underwent overnight polysomnographic and daytime multiple sleep latency testing in order to characterize sleep architecture.

RESULTS: Approximately 18% of persons with CFS and 7% of asymptomatic controls were diagnosed with severe primary sleep disorders and were excluded from further analysis. These rates were not significantly different. Persons with CFS had a significantly higher mean frequency of obstructive apnea per hour (p = .003); however, the difference was not clinically meaningful. Other characteristics of sleep architecture did not differ between persons with CFS and controls.

CONCLUSION: Although disordered breathing during sleep may be associated with CFS, this study generally did not provide evidence that altered sleep architecture is a critical factor in CFS. Future studies should further scrutinize the relationship between subjective sleep quality relative to objective polysomnographic measures.

 

Source: Reeves WC, Heim C, Maloney EM, Youngblood LS, Unger ER, Decker MJ, Jones JF, Rye DB. Sleep characteristics of persons with chronic fatigue syndrome and non-fatigued controls: results from a population-based study. BMC Neurol. 2006 Nov 16;6:41. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1660569/ (Full article)

 

The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study

Abstract:

OBJECTIVES: Fibromyalgia (FMS) and chronic fatigue syndrome (CFS) are debilitating syndromes that are often associated with impaired cellular energy metabolism. As D-ribose has been shown to increase cellular energy synthesis in heart and skeletal muscle, this open-label uncontrolled pilot study was done to evaluate if D-ribose could improve symptoms in fibromyalgia and/or chronic fatigue syndrome patients.

DESIGN: Forty-one (41) patients with a diagnosis of FMS and/or CFS were given D-ribose, a naturally occurring pentose carbohydrate, at a dose of 5 g t.i.d. for a total of 280 g. All patients completed questionnaires containing discrete visual analog scales and a global assessment pre- and post-D-ribose administration.

RESULTS: D-ribose, which was well-tolerated, resulted in a significant improvement in all five visual analog scale (VAS) categories: energy; sleep; mental clarity; pain intensity; and well-being, as well as an improvement in patients’ global assessment. Approximately 66% of patients experienced significant improvement while on D-ribose, with an average increase in energy on the VAS of 45% and an average improvement in overall well-being of 30% (p < 0.0001).

CONCLUSIONS: D-ribose significantly reduced clinical symptoms in patients suffering from fibromyalgia and chronic fatigue syndrome.

 

Source: Teitelbaum JE, Johnson C, St Cyr J. The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study. J Altern Complement Med. 2006 Nov;12(9):857-62. https://www.ncbi.nlm.nih.gov/pubmed/17109576

 

A case control study of premorbid and currently reported physical activity levels in chronic fatigue syndrome

Abstract:

BACKGROUND: Patients with chronic fatigue syndrome typically report high levels of physical activity before becoming ill. Few studies have examined premorbid and current activity levels in chronically fatigued patients.

METHODS: In a case-control study, 33 patients with chronic, unexplained, disabling fatigue attending a university-based clinic specializing in fatigue were compared to 33 healthy, age- and sex-matched controls. Patients rated their activity levels before their illness and currently, using scales designed for this purpose. Controls reported their level of activity of 2 years previously and currently. Chi-square analyses, Student’s t tests, and Wilcoxon signed rank tests were used in pair matched analyses.

RESULTS: Compared to healthy controls, patients with chronic, unexplained fatigue rated themselves as more active before their illness (p < or = 0.001) and less active currently (p < or = 0.001). The patients also reported they currently stood or walked less than the controls (median [inter-quartile range] = 4 2345 versus 9 [7.5-12] hours, p < or = 0.001), and spent more time reclining (median [inter-quartile range] = 12 10111213141516 versus 8 [8-9.5] hours, p < or = 0.001). These differences remained significant for the subset of patients who met strict criteria for chronic fatigue syndrome or fibromyalgia.

CONCLUSION: Patients with chronic, unexplained, disabling fatigue reported being more active before becoming ill than healthy controls. This finding could be explained by greater premorbid activity levels that could predispose to illness, or by an overestimation of previous activity. Either possibility could influence patients’ perceptions of their current activity levels and their judgments of recovery. Perceived activity should be addressed as part of management of the illness.

 

Source: Smith WR, White PD, Buchwald D. A case control study of premorbid and currently reported physical activity levels in chronic fatigue syndrome. BMC Psychiatry. 2006 Nov 13;6:53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1647270/ (Full article)

 

Cognitive dysfunction in fibromyalgia and chronic fatigue syndrome: new trends and future directions

Abstract:

Fibromyalgia (FM) and chronic fatigue syndrome (CFS) patients often have memory and cognitive complaints. Objective cognitive testing demonstrates long-term and working memory impairments. In addition, CFS patients have slow information-processing, and FM patients have impaired control of attention, perhaps due to chronic pain. Neuroimaging studies demonstrate cerebral abnormalities and a pattern of increased neural recruitment during cognitive tasks. Future work should focus on the specific neurocognitive systems involved in cognitive dysfunction in each syndrome.

 

Source: Glass JM. Cognitive dysfunction in fibromyalgia and chronic fatigue syndrome: new trends and future directions. Curr Rheumatol Rep. 2006 Dec;8(6):425-9. https://www.ncbi.nlm.nih.gov/pubmed/17092441

 

Premorbid predictors of chronic fatigue

Abstract:

CONTEXT: Chronic fatigue syndrome is a disabling problem characterized by persistent fatigue lasting at least 6 months with a number of ancillary symptoms. Although the etiology of chronic fatiguing illness is unknown, some evidence suggests that stress may confer increased risk for development of the disorder. Moreover, subjects with chronic fatiguing illness may have distinctive personality traits, although this finding could reflect confounding by other mechanisms.

OBJECTIVE: To assess the prospective association of premorbid self-reported stress and personality with chronic fatigue-like illness.

DESIGN: Prospective nested case-control study in a population-based sample.

SETTING: General community.

PARTICIPANTS: From the Swedish Twin Registry, 19,192 twins born between January 1, 1935, and December 31, 1958.

MAIN OUTCOME MEASURES: Information about current chronic fatiguing illnesses was obtained from computer-assisted telephone interviews conducted between 1998 and 2002. Self-reported stress (based on a single question) and personality scales (emotional instability and extraversion in the Eysenck Personality Inventory) were measured from 1972 to 1973 by a mailed questionnaire. Relative risks were estimated with case-control analyses (matched for age and sex) and co-twin control analyses (comparing discordant pairs).

RESULTS: Higher emotional instability and self-reported stress in the premorbid period were associated with higher risk for chronic fatigue-like illness in matched case-control analyses (odds ratios, 1.72 and 1.64, respectively). In co-twin control analyses, relative risk of emotional instability decreased to 1.02 whereas that of stress increased considerably to 5.81. There was no association between extraversion and fatigue.

CONCLUSIONS: Elevated premorbid stress is a significant risk factor for chronic fatigue-like illness, the effect of which may be buffered by genetic influences. Emotional instability assessed 25 years earlier is associated with chronic fatigue through genetic mechanisms contributing to both personality style and expression of the disorder. These findings suggest plausible mechanisms for chronic fatiguing illness.

 

Source: Kato K, Sullivan PF, Evengård B, Pedersen NL. Premorbid predictors of chronic fatigue. Arch Gen Psychiatry. 2006 Nov;63(11):1267-72. https://www.ncbi.nlm.nih.gov/pubmed/17088507

 

Early adverse experience and risk for chronic fatigue syndrome: results from a population-based study

Abstract:

CONTEXT: Chronic fatigue syndrome (CFS) is an important public health problem. The causes of CFS are unknown and effective prevention strategies remain elusive. A growing literature suggests that early adverse experience increases the risk for a range of negative health outcomes, including fatiguing illnesses. Identification of developmental risk factors for CFS is critical to inform pathophysiological research and devise targets for primary prevention.

OBJECTIVE: To examine the relationship between early adverse experience and risk for CFS in a population-based sample of clinically confirmed CFS cases and nonfatigued control subjects.

DESIGN, SETTING, AND PARTICIPANTS: A case-control study of 43 cases with current CFS and 60 nonfatigued controls identified from a general population sample of 56 146 adult residents from Wichita, Kan.

MAIN OUTCOME MEASURES: Self-reported childhood trauma (sexual, physical, and emotional abuse and emotional and physical neglect) and psychopathology (depression, anxiety, and posttraumatic stress disorder) by CFS status.

RESULTS: The CFS cases reported significantly higher levels of childhood trauma and psychopathology compared with the controls. Exposure to childhood trauma was associated with a 3- to 8-fold increased risk for CFS across different trauma types. There was a graded relationship between the degree of trauma exposure and CFS risk. Childhood trauma was associated with greater CFS symptom severity and with symptoms of depression, anxiety, and posttraumatic stress disorder. The risk for CFS conveyed by childhood trauma increased with the presence of concurrent psychopathology.

CONCLUSIONS: This study provides evidence of increased levels of multiple types of childhood trauma in a population-based sample of clinically confirmed CFS cases compared with nonfatigued controls. Our results suggest that childhood trauma is an important risk factor for CFS. This risk was in part associated with altered emotional state. Studies scrutinizing the psychological and neurobiological mechanisms that translate childhood adversity into CFS risk may provide direct targets for the early prevention of CFS.

 

Source: Heim C, Wagner D, Maloney E, Papanicolaou DA, Solomon L, Jones JF, Unger ER, Reeves WC. Early adverse experience and risk for chronic fatigue syndrome: results from a population-based study. Arch Gen Psychiatry. 2006 Nov;63(11):1258-66. https://www.ncbi.nlm.nih.gov/pubmed/17088506

 

A follow-up study of chronic fatigue syndrome in children and adolescents: symptom persistence and school absenteeism

Abstract:

This is a follow-up study of 28 young people aged between 7 and 17 meeting the Oxford criteria for the diagnosis of chronic fatigue syndrome treated in a specialist paediatric/psychiatric service. Retrospective case note analysis revealed a wide range and duration of symptoms together with high levels of school absenteeism prior to the diagnosis. The mean follow-up interval after discharge from the specialist service was 3 years and although most of the young people regarded themselves as fully recovered by this time, improvement was variable and about one third were still experiencing disabling symptoms.

The illness had impacted on the education or career plans of all the young people to some extent with 15 experiencing difficulty returning to school. This article highlights the need for early recognition and diagnosis of chronic fatigue syndrome in young people and the importance of continuing paediatric support to reduce symptom persistence in the sensitive recovery period. Maintaining school attendance by close liaison between health and education services both before and after diagnosis and treatment is also vital if long-term morbidity is to be reduced.

 

Source: Sankey A, Hill CM, Brown J, Quinn L, Fletcher A. A follow-up study of chronic fatigue syndrome in children and adolescents: symptom persistence and school absenteeism. Clin Child Psychol Psychiatry. 2006 Jan;11(1):126-38. https://www.ncbi.nlm.nih.gov/pubmed/17087490

 

Long-term efficacy of cognitive-behavioral therapy by general practitioners for fatigue: a 4-year follow-up study

Abstract:

OBJECTIVE: In an earlier study, we found that cognitive-behavioral therapy (CBT) delivered by general practitioners (GPs) for fatigue among employees on sick leave was not effective after 12 months. In this study we aim to assess the long-term efficacy of CBT by GPs for fatigue. It was hypothesized that the intervention could prevent deterioration as well as relapse of fatigue complaints and relapse into absenteeism in the long term.

METHODS: Patients who participated in the original randomized controlled trial were followed up 4 years later. Fatigue and absenteeism were the main outcomes.

RESULTS: Fatigue and absenteeism were high in the intervention and control groups at the 4-year follow-up. There was no significant difference between the intervention group and the control group on fatigue and absenteeism. The intervention group however tended toward less-favorable outcomes as compared with the control group.

CONCLUSIONS: Like that of chronic fatigue syndrome, the prognosis of less-advanced fatigue is rather poor. CBT delivered by GPs is not effective in the long term.

 

Source: Leone SS, Huibers MJ, Kant I, van Amelsvoort LG, van Schayck CP, Bleijenberg G, Knottnerus JA. Long-term efficacy of cognitive-behavioral therapy by general practitioners for fatigue: a 4-year follow-up study. J Psychosom Res. 2006 Nov;61(5):601-7. https://www.ncbi.nlm.nih.gov/pubmed/17084137

 

Probing the working memory system in chronic fatigue syndrome: a functional magnetic resonance imaging study using the n-back task

Abstract:

OBJECTIVE: Up to 90% of patients with chronic fatigue syndrome (CFS) report substantial cognitive difficulties. However, objective evidence supporting these claims is inconsistent. The present functional magnetic resonance imaging study examined the neural correlates of working memory in patients with CFS compared with controls.

METHODS: Seventeen patients with CFS and 12 healthy control subjects were scanned while performing a parametric version of the n-back task (0-, 1-, 2-, and 3-back).

RESULTS: Both groups performed comparably well and activated the verbal working memory network during all task levels. However, during the 1-back condition, patients with CFS showed greater activation than control subjects in medial prefrontal regions, including the anterior cingulate gyrus. Conversely, on the more challenging conditions, patients with CFS demonstrated reduced activation in dorsolateral prefrontal and parietal cortices. Furthermore, on the 2- and 3-back conditions, patients but not control subjects significantly activated a large cluster in the right inferior/medial temporal cortex. Trend analyses of task load demonstrated statistically significant differences in brain activation between the two groups as the demands of the task increased.

CONCLUSIONS: These results suggest that patients with CFS show both quantitative and qualitative differences in activation of the working memory network compared with healthy control subjects. It remains to be determined whether these findings stay stable after successful treatment.

 

Source: Caseras X, Mataix-Cols D, Giampietro V, Rimes KA, Brammer M, Zelaya F, Chalder T, Godfrey EL. Probing the working memory system in chronic fatigue syndrome: a functional magnetic resonance imaging study using the n-back task. Psychosom Med. 2006 Nov-Dec;68(6):947-55. Epub 2006 Nov 1. https://www.ncbi.nlm.nih.gov/pubmed/17079703