In 1869 George Miller Beard, coined the concept of neurasthenia, which is now commonly known as chronic fatigue syndrome. Chronic fatigue syndrome is a debilitating and complex disorder, wherein patients experience profound fatigue that does not improve with bed rest (see Box 1). Physical or mental activity is likely to aggravate the condition. Symptoms involving several body systems include weakness, muscle pain, impaired memory and/or mental concentration, and insomnia. Chronic fatigue syndrome is often misdiagnosed as depression.
Chronic fatigue syndrome is significant comorbidity for psychiatric disorders. Symptoms of chronic fatigue syndrome often overlap with psychiatric disorders; nevertheless it is not included in the Diagnostic and Statistical Manual of Mental Disorders. Chronic fatigue is frequently observed in women in developing countries. Psychological factors, such as symptoms of common mental disorders and somatoform disorders, and marital sexual violence are strongly associated with chronic fatigue. The etiology of chronic fatigue syndrome is not well defined, but familial predisposition or a genetic link, loss of immunologic tolerance, hypothalamic-pituitaryadrenal (HPA) axis abnormalities and viral infections has been associated as a causative factor.
Chronic fatigue syndrome and fibromyalgia are diagnostically different entities, nevertheless, there is overlapping of clinical feature between the two conditions. Therefore, understanding of pain related to chronic fatigue syndrome within the biopsychosocial is necessary to provide pain physiology education.
Chronic Fatigue Syndrome: A Debilitating Condition
The prevalence of unexplained fatigue of one month's duration was in the range of 2.3–15.1%. The prevalence of chronic fatigue syndrome was widespread and indicative of psychosocial distress in developed countries. Symptoms of chronic fatigue syndrome together substantially affect occupational, personal, social, and educational status of patients. Patients with chronic fatigue syndrome experience significant functional impairment.
Irrespective of the geographic distribution, the healthrelated quality of life is poor in chronic fatigue syndrome patients. In fact, up to 34% of the patients with chronic pain reported limitations in activity. In a study, the quality of life of patients with chronic fatigue syndrome were assessed using the recent international EQ-5D based health-related quality of life. The poor quality of life was evident as The EQ-5D-3L-based health-related quality of life of chronic fatigue syndrome was significantly lower than the general population mean and the lowest of all the compared conditions (see Fig. 8). The unadjusted EQ-5D-3L mean of chronic fatigue syndrome was 0.47 [0.41–0.53] while that of population was 0.85 [0.84–0.86]. Chronic fatigue syndrome patients’ most frequent score and center are around 0.6 (see Fig. 9).
In a community survey from Goa, subjects experiencing chronic fatigue had significantly poorer WHO disability assessment schedule scores when compared to control subjects (mean score 14.1(SD 2.5) vs. 12.4(1.3); t= 19.03, p<0.001)
Occupational disability is one of the adverse consequences of chronic fatigue syndrome. Patients with longterm sickness absence reported significantly more physical fatigue (p<0.05) and poor sleep (p<0.05). In addition they reported poor cognitive and behavioral responses, which were measured in terms of embarrassment over symptoms and avoidant behavior.
Pain: A Unique Feature of CFS
Besides fatigue, chronic widespread pain is a hallmark symptom in majority of patients with chronic fatigue syndrome. Chronic pain is viewed as the most disabling factor than chronic fatigue. According to a populationbased study, 94% of the persons with confirmed diagnosis of chronic fatigue syndrome had complaints of muscle aches and pain and 84% of them had joint pain. In another study, nearly three-fourth (74.6%) of the patients with chronic fatigue syndrome reported muscle pain and 65% of them complained of arthralgia.
In the absence of peripheral tissue damage and lack of a distinct localization of the pain complaints in chronic fatigue syndrome, a central sensitization hypothesis has been suggested for the chronic widespread pain in patients with chronic fatigue syndrome. In adolescents with chronic fatigue syndrome, the threshold for pain was much lower than healthy controls Headache, abdominal pain and/or pain in muscles and joints were frequently observed in adolescents with chronic fatigue syndrome compared to healthy controls (see Fig. 10). In all these sites, the intensity of pain were significantly higher in those with chronic fatigue syndrome than healthy controls reported more than four sites as painful but there were none in the healthy control group. At all measure points, pressure pain thresholds were significantly lower (all p<0.001) those with chronic fatigue syndrome than healthy controls (see Fig. 11).
Understanding Pain in Patients with Chronic Fatigue Syndrome
Unexplained chronic musculoskeletal pain is usually thought to occur the central sensitization, which is characterized by the inhibition of descending antinociceptive mechanism and (over)activation of descending and ascending pain facilitatory pathways. Ultimately, there is an augmentation of nociceptive transmission. There is a lack of evidence in support of central sensitization hypothesis in manifestation of pain in patients with chronic fatigue syndrome. Nitric oxide (NO) modulates the nociceptive process in the brain. Low levels of NO are beneficial as it inhibits the nociceptive pathways; however at higher concentrations, NO influences the central sensitization, which leads to generalized or widespread hypersensitivity to a variety of stimuli. Elevated NO levels have been documented in CFS patients.
Nevertheless, evidence on the role of NO in the pathogenesis of pain in chronic fatigue syndrome is insufficient. Hyperalgesia at different sites is a significant finding in patients with chronic fatigue syndrome. Clinical trials examining the level of pain threshold suggest the involvement of a generalized hyperexcitability of central nociceptive pathways in producing pain in patients with chronic fatigue syndrome. Serotonergic abnormalities have been implicated in the dysfunctionality of endogenous analgesia in patients with chronic fatigue syndrome. However, patients with chronic fatigue syndrome lack endogenous analgesia in response to exercise. Thus, musculoskeletal factors perhaps may not be accountable for pain arising from chronic fatigue syndrome. Pain appears to be one of the several symptoms of central sensitization in chronic fatigue syndrome.