The association between experimental and clinical pain measures among persons with fibromyalgia and chronic fatigue syndrome

Abstract:

Evoked or experimental pain is often used as a model for the study of clinical pain, yet there are little data regarding the relationship between the two. In addition, there are few data regarding the types of stimuli and stimulus intensities that are most closely related to clinical pain. In this study, 36 subjects with fibromyalgia (FM), chronic fatigue syndrome (CFS), or both syndromes were administered measures of clinical pain and underwent a dolorimetry evaluation. Subjects also underwent experimental pain testing utilizing heat and pressure stimulation.

Stimulation levels evoking low, moderate and high sensory intensity, and comparable levels of unpleasantness, were determined for both types of stimuli using random staircase methods. Clinical pain was assessed using visual analogue ratings and the short form of the McGill Pain Questionnaire (MPQ). Ratings of heat pain sensation were not significantly associated with clinical pain ratings, with the exception of unpleasantness ratings at high stimulus intensities. Pain threshold and tolerance as assessed by dolorimetry were significantly associated with average measures of clinical pain.

Both intensity and unpleasantness ratings of pressure delivered using random staircase methods were significantly associated with clinical pain at low, moderate and high levels, and the strength of the association was greater at increasingly noxious stimulus intensities. These findings suggest that random pressure stimulation as an experimental pain model in these populations more closely reflects the clinical pain for these conditions. These findings merit consideration when designing experimental studies of clinical pain associated with FM and CFS.

 

Source: Geisser ME, Gracely RH, Giesecke T, Petzke FW, Williams DA, Clauw DJ. The association between experimental and clinical pain measures among persons with fibromyalgia and chronic fatigue syndrome. Eur J Pain. 2007 Feb;11(2):202-7. Epub 2006 Mar 20. https://www.ncbi.nlm.nih.gov/pubmed/16546424

 

Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise

Abstract:

OBJECTIVES: Because the muscle response to incremental exercise is not well documented in patients suffering from chronic fatigue syndrome(CFS), we combined electrophysiological (compound-evoked muscle action potential, M wave), and biochemical (lactic acid production, oxidative stress) measurements to assess any muscle dysfunction in response to a routine cycling exercise.

DESIGN: This case-control study compared 15 CFS patients to a gender-, age- and weight-matched control group (n=11) of healthy subjects.

INTERVENTIONS: All subjects performed an incremental cycling exercise continued until exhaustion.

MAIN OUTCOME MEASURES: We measured the oxygen uptake (VO2), heart rate (HR), systemic blood pressure, percutaneous O2 saturation (SpO2), M-wave recording from vastus lateralis, and venous blood sampling allowing measurements of pH (pHv), PO2 (PvO2), lactic acid (LA), and three markers of the oxidative stress (thiobarbituric acid-reactive substances, TBARS, reduced glutathione, GSH, and ascorbic acid, RAA).

RESULTS: Compared with control, in CFS patients (i) the slope of VO2 versus work load relationship did not differ from control subjects and there was a tendency for an accentuated PvO2 fall at the same exercise intensity, indicating an increased oxygen uptake by the exercising muscles; (ii) the HR and blood pressure responses to exercise did not vary; (iii) the anaerobic pathways were not accentuated; (iv) the exercise-induced oxidative stress was enhanced with early changes in TBARS and RAA and enhanced maximal RAA consumption; and (v) the M-wave duration markedly increased during the recovery period.

CONCLUSIONS: The response of CFS patients to incremental exercise associates a lengthened and accentuated oxidative stress together with marked alterations of the muscle membrane excitability. These two objective signs of muscle dysfunction are sufficient to explain muscle pain and postexertional malaise reported by our patients.

 

Source: Jammes Y, Steinberg JG, Mambrini O, Brégeon F, Delliaux S. Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise. J Intern Med. 2005 Mar;257(3):299-310. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2005.01452.x/full (Full article)

 

Chronic fatigue syndrome: lack of association between pain-related fear of movement and exercise capacity and disability

Abstract:

BACKGROUND AND PURPOSE: Patients who experience pain, a symptom of chronic fatigue syndrome (CFS), often exhibit kinesiophobia (irrational fear of movement). The purpose of this study was to examine whether pain-related fear of movement is associated with exercise capacity, activity limitations, or participation restrictions in patients with CFS who experience widespread pain.

SUBJECTS AND METHODS: Sixty-four subjects met the inclusion criteria. All subjects fulfilled the 1994 Centers for Disease Control and Prevention case definition for CFS and experienced widespread myalgias or arthralgias. The subjects completed the Tampa Scale for Kinesiophobia-Dutch Version (TSK-DV) and the Dutch Chronic Fatigue Syndrome-Activities and Participation Questionnaire (CFS-APQ). They then performed a maximal exercise test on a bicycle ergometer. Heart rate was monitored continuously by use of an electrocardiograph. Ventilatory factors were measured through spirometry. Correlations between the TSK-DV scores and both the exercise capacity data and the CFS-APQ scores were assessed using the Spearman rank correlation coefficient. Using the Mann-Whitney U test, the TSK-DV scores were compared between subjects who performed a maximal exercise stress test and those who did not perform the test.

RESULTS: Forty-seven subjects (73.4%) attained a total score of greater than 37 on the TSK-DV, indicating high fear of movement. Neither the exercise capacity data nor the CFS-APQ scores indicated a correlation with the TSK-DV scores (n=64). Subjects who did not perform a maximal exercise capacity test had more fear of movement (median TSK-DV score=43.0, interquartile range=10.3) compared with those who did perform a maximal exercise capacity test (median TSK-DV score=38.0, interquartile range=13.2; Mann-Whitney U-test score=322.5, z=-1.974, P=.048), but the correlation analysis was unable to reveal an association between exercise capacity and kinesiophobia in either subgroup.

DISCUSSION AND CONCLUSION: These results indicate a lack of correlation between kinesiophobia and exercise capacity, activity limitations, or participation restrictions, at least in patients with CFS who are experiencing widespread muscle or joint pain.

 

Source: Nijs J, Vanherberghen K, Duquet W, De Meirleir K. Chronic fatigue syndrome: lack of association between pain-related fear of movement and exercise capacity and disability. Phys Ther. 2004 Aug;84(8):696-705. http://ptjournal.apta.org/content/84/8/696.long (Full article)

 

Exercise lowers pain threshold in chronic fatigue syndrome

Abstract:

Post-exertional muscle pain is an important reason for disability in patients who are diagnosed to have Chronic Fatigue Syndrome (CFS). We compared changes in pain threshold in five CFS patients with five age and sex matched controls following graded exercise. Pain thresholds, measured in the skin web between thumb and index finger, increased in control subjects with exercise while it decreased in the CFS subjects. Increased perception of pain and/or fatigue after exercise may be indicative of a dysfunction of the central anti-nociceptive mechanism in CFS patients.

 

Source: Whiteside A, Hansen S, Chaudhuri A. Exercise lowers pain threshold in chronic fatigue syndrome. Pain. 2004 Jun;109(3):497-9. http://www.ncbi.nlm.nih.gov/pubmed/15157711

 

Chronic diffuse musculoskeletal pain, fibromyalgia and co-morbid unexplained clinical conditions

Abstract:

This chapter reviews our current knowledge on the presence of overlapping syndromes in one form of chronic diffuse pain, fibromyalgia. Patients with fibromyalgia often present with signs and symptoms of other unexplained clinical conditions, including chronic fatigue syndrome, irritable bowel syndrome, temporomandibular disorders, and multiple chemical sensitivities. The high prevalence, impact on function and opportunities for treatment underscore the need for clinicians and researchers to screen routinely for co-morbid unexplained clinical conditions among persons with fibromyalgia. We, therefore, describe a simple approach to screening for such conditions in accordance with published criteria. Interventions should directly address both fibromyalgia symptoms and co-morbid unexplained clinical conditions, as well as the multiple factors that propagate pain, fatigue and limitations in function.

 

Source: Aaron LA, Buchwald D. Chronic diffuse musculoskeletal pain, fibromyalgia and co-morbid unexplained clinical conditions. Best Pract Res Clin Rheumatol. 2003 Aug;17(4):563-74. http://www.ncbi.nlm.nih.gov/pubmed/12849712

 

Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome

Abstract:

In 21 patients with chronic fatigue syndrome (CFS) versus 20 normal subjects, we investigated the oxidant/antioxidant balance and its correlation with muscle symptoms. Patients versus controls showed significantly: lower Lag Phase and Vitamin E (Vit E) concentrations in plasma and low-density lipoproteins (LDL), higher LDL thiobarbituric acid reactive substances (TBARS), higher fatigue and lower muscle pain thresholds to electrical stimulation.

A significant direct linear correlation was found between fatigue and TBARS, thresholds and Lag Phase, thresholds and Vit E in plasma and LDL. A significant inverse linear correlation was found between fatigue and Lag Phase, fatigue and Vit E, thresholds and TBARS. Increased oxidative stress and decreased antioxidant defenses are related to the extent of symptomatology in CFS, suggesting that antioxidant supplementation might relieve muscle symptoms in the syndrome.

 

Source: Vecchiet J, Cipollone F, Falasca K, Mezzetti A, Pizzigallo E, Bucciarelli T, De Laurentis S, Affaitati G, De Cesare D, Giamberardino MA. Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome. Neurosci Lett. 2003 Jan 2;335(3):151-4. http://www.ncbi.nlm.nih.gov/pubmed/12531455

 

A tender sinus does not always mean rhinosinusitis

Abstract:

BACKGROUND: Sinus tenderness has not been quantitatively assessed.

OBJECTIVE: We sought to compare sinus and systemic tenderness in rhinosinusitis, allergic rhinitis, and chronic fatigue syndrome (CFS), and healthy (non-CFS) groups.

METHODS: Cutaneous pressures (kg/cm(2)) causing pain at 5 sinus and 18 systemic sites were measured in acute and chronic rhinosinusitis, active allergic rhinitis, healthy non-CFS/no rhinosinusitis, and CFS subjects.

RESULTS: Sinus thresholds differed significantly (P </= 10(-11), ANOVA) between non-CFS/no rhinosinusitis (1.59 +/- 0.14 kg/cm(2), mean +/- 95% CI, n = 117), allergic rhinitis (1.19 +/- 0.31, n = 30), exacerbations of chronic rhinosinusitis (1.25 +/- 0.26, n = 25), non-CFS/chronic rhinosinusitis (1.23 +/- 0.27, n = 23), acute rhinosinusitis (1.10 +/- 0.20, n = 22), CFS/no rhinosinusitis (0.98 +/- 0.15, n = 70), and CFS/chronic rhinosinusitis (0.78 +/- 0.12, n = 56). Systemic pressure thresholds were lower for CFS (1.46 +/- 0.15) than for non-CFS (2.67 +/- 0.22, P </= 10(-11)).

CONCLUSIONS: The lower sinus thresholds of rhinosinusitis groups validated the sign of sinus tenderness. Sinus and systemic thresholds were both 44% lower in CFS than in non-CFS subjects, suggesting that systemic hyperalgesia contributed to CFS sinus tenderness and “rhinosinusitis” complaints.

 

Source: Naranch K, Park YJ, Repka-Ramirez MS, Velarde A, Clauw D, Baraniuk JN. A tender sinus does not always mean rhinosinusitis. Otolaryngol Head Neck Surg. 2002 Nov;127(5):387-97. http://www.ncbi.nlm.nih.gov/pubmed/12447232

 

Health and functional status of twins with chronic regional and widespread pain

Erratum in: J Rheumatol. 2002 Dec;29(12):2667. Buchwald, Dedra [corrected to Buchwald, Debra].

 

Abstract:

OBJECTIVE: To examine the independent effects of chronic regional and widespread pain syndromes on health and functional status after accounting for comorbid chronic fatigue using a co-twin control design.

METHODS: We identified 95 twin pairs discordant for pain in which one twin had chronic regional or widespread pain and the other denied chronic pain. Demographic data, functional and psychological status, health behaviors, and symptoms based on the 1994 criteria for chronic fatigue syndrome (CFS) were assessed by questionnaire. Psychiatric diagnoses were based on structured interview. Random effects regression modeling estimated associations between chronic regional and widespread pain and each health measure with and without adjustment for CFS.

RESULTS: Significant differences (p </= 0.05) were found within twin pairs discordant for chronic regional and widespread pain, for general health perception, and physical and mental health functioning as measured by summary scores from the Short Form-36. In addition, differences were observed within pain discordant pairs in psychological distress as measured by the General Health Questionnaire as well as the number of psychiatric diagnoses. Adjustment for CFS eliminated the association between chronic pain and mental health, but the association between chronic pain and poor general health, physical functioning, and sleep quality persisted (p </= 0.01). Only the intra-pair difference in physical functioning distinguished twins with regional vs widespread pain (p </= 0.05).

CONCLUSION: Both chronic regional and widespread pain exact debilitating effects on perceived general health, physical functioning, and sleep quality independent of CFS. However, the psychological and psychiatric influence of chronic pain appears closely tied to CFS. Research should examine the additive role of CFS-like illnesses in patients with chronic pain, and its influence on treatment and outcome.

 

Source: Aaron LA, Arguelles LM, Ashton S, Belcourt M, Herrell R, Goldberg J, Smith WR, Buchwald D. Health and functional status of twins with chronic regional and widespread pain. J Rheumatol. 2002 Nov;29(11):2426-34. http://www.ncbi.nlm.nih.gov/pubmed/12415604

 

Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome

Abstract:

The prevalence of chronic widespread pain in the general population in Israel was comparable with reports from the USA, UK, and Canada. Comorbidity with fibromyalgia (FM) resulted in somatic hyperalgesia in patients with irritable bowel syndrome. One sixth of the subjects with chronic widespread pain in the general population were also found to have a mental disorder.

Mechanisms involved in referred pain, temporal summation, muscle hyperalgesia, and muscle pain at rest were attenuated by the N-methyl-D-aspartate (NMDA) antagonist, ketamine, in FM patients. Delayed corticotropin release, after interleukin-6 administration, in FM was shown to be consistent with a defect in hypothalamic corticotropin-releasing hormone neural function. The basal autonomic state of FM patients was characterized by increased sympathetic and decreased parasympathetic systems tones.

The severity of functional impairment as assessed by the Medical Outcome Survey Short Form (SF-36) discriminated between patients with widespread pain alone and FM patients. Chronic fatigue syndrome (CFS) occurred in about 0.42% of a random community-based sample of 28,673 adults in Chicago, Illinois.

A significant clinical overlap between CFS and FM was reported. Cytokine dysregulation was not found to be a singular or dominant factor in the pathogenesis of CFS. A favorable outcome of CFS in children was reported; two thirds recovered and resumed normal activities. No major therapeutic trials in FM and CFS were reported over the past year.

 

Source: Buskila D. Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome. Curr Opin Rheumatol. 2001 Mar;13(2):117-27. http://www.ncbi.nlm.nih.gov/pubmed/11224736

 

Pain complaints in patients with fibromyalgia versus chronic fatigue syndrome

Abstract:

Individuals with fibromyalgia (FM) and/or chronic fatigue syndrome (CFS) report arthralgias and myalgias. However, only persons with FM alone exhibit abnormal pain responses to mild levels of stimulation, or allodynia. We identify the abnormalities in the neuroendocrine axes that are common to FM and CFS as well as the abnormalities in central neuropeptide levels and functional brain activity that differentiate these disorders. These two sets of factors, respectively, may account for the similarities and differences in the pain experiences of persons with FM and CFS.

 

Source: Bradley LA, McKendree-Smith NL, Alarcón GS. Pain complaints in patients with fibromyalgia versus chronic fatigue syndrome. Curr Rev Pain. 2000;4(2):148-57. http://www.ncbi.nlm.nih.gov/pubmed/10998728