Perspectives on Fatigue from the Study of Chronic Fatigue Syndrome and Related Conditions

Fatigue is a symptom whose causes are protean and whose phenotype includes physical, mood, and behavioral components. Chronic fatigue syndrome (CFS) is an illness that has strong biological underpinnings and no definite etiology. Diagnostic criteria established by the Centers for Disease Control and Prevention have helped classify CFS as an overlap of mood, behavioral, and biological components. These include the presence of fatigue for more than 6 months associated with a diminution of functional activity and somatic symptoms, and pain not attributable to a specific diagnosis or disease. Four of the following criteria need to be present: sore throat, impaired memory or cognition, unrefreshing sleep, postexertional fatigue, tender glands, aching stiff muscles, joint pain, and headaches. Many researchers have observed that CFS shares features in common with other somatic syndromes, including irritable bowel syndrome, fibromyalgia, and temporomandibular joint dysfunction. Correlations between inflammation and infection, augmented sensory processing, abnormalities of neurotransmitters, nerve growth factors, low levels of serotonin and norepinephrine, abnormalities of homeostasis of the stress system, and autonomic dysfunction may be hallmarks of CFS. The relative contributions of each of these abnormalities to the profound fatigue associated with CFS need to be explored further to better evaluate and treat the syndrome.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147220/1/pmr2414.pd

Central pain mechanisms in the rheumatic diseases: Future directions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96384/1/37739_ftp.pd

Newer treatments for fibromyalgia syndrome

Fibromyalgia syndrome is a common chronic pain disorder of unknown etiology. The lack of understanding of the pathophysiology of fibromyalgia has made this condition frustrating for patients and clinicians alike. The most common symptoms of this disorder are chronic widespread pain, fatigue, sleep disturbances, difficulty with memory, and morning stiffness. Emerging evidence points towards augmented pain processing within the central nervous system (CNS) as having a primary role in the pathophysiology of this disorder. Currently the two drugs that are approved by the United States Food and Drug Administration (FDA) for the management of fibromyalgia are pregabalin and duloxetine. Newer data suggests that milnacipran, a dual norepinephrine and serotonin reuptake inhibitor, may be promising for the treatment of fibromyalgia. A double-blind, placebo-controlled trial of milnacipran in 125 fibromyalgia patients showed significant improvements relative to placebo. Milnacipran given either once or twice daily at doses up to 200 mg/day was generally well tolerated and yielded significant improvements relative to placebo on measures of pain, patient’s global impression of change in their disease state, physical function, and fatigue. Future studies are needed to validate the efficacy of milnacipran in fibromyalgia

Clinical Characteristics, Pharmacotherapy and Healthcare Resource Use among Patients with Fibromyalgia Newly Prescribed Gabapentin or Pregabalin

Objective:  To characterize comorbidities, pain-related pharmacotherapy, and healthcare resource use among patients with fibromyalgia (FM) newly prescribed pregabalin or gabapentin in clinical practice. Methods and design:  Using the PharMetrics ® Database, FM patients (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1X) newly prescribed pregabalin ( n  = 1,606; mean age 49.9 ± 9.6 years; 87.9% female) and gabapentin ( n  = 930; mean age 49.5 ± 9.6 years; 86.6% female) on/after July 1, 2007 were identified. Prevalence of comorbidities, pharmacotherapy, and healthcare resource use/costs (pharmacy, outpatient, inpatient, total) were examined during the 6 months preceding (preindex) and following (postindex) the date of their first pregabalin or gabapentin (index) prescription. Results:  Patients in both cohorts had a variety of comorbidities and used multiple medications. There were significant decreases ( P values < 0.05) in the use of nonsteroidal anti-inflammatory drugs (32.1% vs. 29.5%), anticonvulsants (27.0% vs. 22.0%), and combination therapies in the pregabalin cohort in the postindex period. There were significant increases (all P values < 0.05) in use of short-acting opioids (58.8% vs. 63.7%), any opioids (61.5% vs. 65.6%), serotonin–norepinephrine reuptake inhibitors (22.5% vs. 24.5%), anticonvulsants (16.3% vs. 26.2%), benzodiazepines (33.2% vs. 36.6%), topical agents (6.6% vs. 9.0%), and combination therapies in the gabapentin cohort. Although there were no changes in units of healthcare resources used, there were increases in the postindex period in hospitalization, medications, and total costs for pregabalin, and office visits and medication costs for gabapentin (all P values < 0.05). Conclusions:  Results suggest a high comorbidity and medication use burden in FM patients in this study. Further evaluation is warranted to clarify differences in resource utilization/costs observed with these two anticonvulsants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73737/1/j.1533-2500.2009.00292.x.pd

Covariates of corticotropin-releasing hormone (CRH) concentrations in cerebrospinal fluid (CSF) from healthy humans

BACKGROUND: Define covariates of cerebrospinal corticotropin-releasing hormone (CRH) levels in normal humans. CRH(CSF )was measured in 9 normal subjects as part of an intensive study of physiological responses stressors in chronic pain and fatigue states. CRH(CSF )was first correlated with demographic, vital sign, HPA axis, validated questionnaire domains, baseline and maximal responses to pain, exercise and other stressors. Significant factors were used for linear regression modeling. RESULTS: Highly significant correlations were found despite the small number of subjects. Three models were defined: (a) CRH(CSF )with blood glucose and sodium (explained variance = 0.979, adjusted R(2 )= 0.958, p = 0.02 by 2-tailed testing); (b) CRH(CSF )with resting respiratory and heart rates (R(2 )= 0.963, adjusted R(2 )= 0.939, p = 0.007); and (c) CRH(CSF )with SF-36 Vitality and Multidimensional Fatigue Inventory Physical Fatigue domains (R(2 )= 0.859, adjusted R(2 )= 0.789, p = 0.02). CONCLUSIONS: Low CRH(CSF )was predicted by lower glucose, respiratory and heart rates, and higher sodium and psychometric constructs of well being. Responses at peak exercise and to other acute stressors were not correlated. CRH(CSF )may have reflected an overall, or chronic, set-point for physiological responses, but did not predict the reserves available to respond to immediate stressors

Biology and therapy of fibromyalgia. Evidence-based biomarkers for fibromyalgia syndrome

Researchers studying fibromyalgia strive to identify objective, measurable biomarkers that may identify susceptible individuals, may facilitate diagnosis, or that parallel activity of the disease. Candidate objective measures range from sophisticated functional neuroimaging to office-ready measures of the pressure pain threshold. A systematic literature review was completed to assess highly investigated, objective measures used in fibromyalgia studies. To date, only experimental pain testing has been shown to coincide with improvements in clinical status in a longitudinal study. Concerted efforts to systematically evaluate additional objective measures in research trials will be vital for ongoing progress in outcome research and translation into clinical practice

The role of environmental distractions in the experience of fibrofog in real-world settings

The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. Supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH (award K01‐AR‐064275; Principal Investigator, Dr. Kratz). The Michigan Institute for Clinical & Health Research (NIH award UL1‐TR‐002240) provided subject recruitment support through the UMHealthResearch.org website.Peer reviewedPublisher PD

Association between pain, radiographic severity, and centrally‐mediated symptoms in women with knee osteoarthritis

Objective To examine the relationship between pain, radiographic severity, and a common set of co‐occurring centrally‐mediated symptoms (fatigue, sleep quality, and depression) in women with knee osteoarthritis. Methods Participants underwent knee radiographs, and had repeated assessments of pain severity and other centrally‐mediated symptoms during a 5‐day home monitoring period. To examine associations between pain severity (the average of pain over the home monitoring period), measures of osteoarthritis radiographic severity (Kellgren/Lawrence grade, minimum joint space width), centrally‐mediated symptoms, and demographics (age) were used. Symptoms of fatigue, sleep efficiency, and depression were used in a composite measure representing centrally‐mediated symptoms. Results Using a series of linear regression models in which each variable was entered hierarchically (n = 54), the final model showed that 27% of the variance in pain severity was explained by age, radiographic severity, and centrally‐mediated symptoms. Centrally‐mediated symptoms explained an additional 10% of the variance in pain severity after the other 2 variables were entered. Conclusion Both radiographic severity and centrally‐mediated symptoms were independently and significantly associated with pain severity in women with knee osteoarthritis. In addition to more severe radiographic features, women with higher centrally‐mediated symptoms had greater pain severity. Treatments for women with symptomatic knee osteoarthritis may be optimized by addressing both peripheral and central sources of pain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88108/1/20583_ftp.pd