Life Extension Magazine July 2005
A review of fibromyalgia.
Characterized by chronic widespread joint and muscle pain, fibromyalgia is a syndrome of unknown etiology. The American College of Rheumatology’s classification criteria for fibromyalgia include diffuse soft tissue pain of at least 3 months’ duration and pain on palpation in at least 11 of 18 paired tender points. Symptoms are often exacerbated by exertion, stress, lack of sleep, and weather changes. Fibromyalgia is primarily a diagnosis of exclusion, established only after other causes of joint or muscle pain are ruled out. The initial workup for patients who present with widespread musculoskeletal pain should include a complete blood count, erythrocyte sedimentation rate, liver function tests, hepatitis C antibody, calcium, and thyrotropin. The musculoskeletal system, the neuroendocrine system, and the central nervous system, particularly the limbic system, appear to play major roles in the pathogenesis of fibromyalgia. The goal in treating fibromyalgia is to decrease pain and to increase function without promoting polypharmacy. Brief interdisciplinary programs have been shown to improve subjective pain. Fibromyalgia is a complex syndrome associated with significant impairment on quality of life and function and substantial financial costs. Once the diagnosis is made, providers should aim to increase patients’ function and minimize pain. This can be accomplished through nonpharmacological ahd pharmacological interventions. With proper management, the rate of disability appears to be significantly reduced.
Am J Manag Care. 2004 Nov;10(11 Pt 1):794-800
Investigation of the hypothalamo-pituitary-adrenal axis (HPA) by 1 microg ACTH test and metyrapone test in patients with primary fibromyalgia syndrome.
Primary fibromyalgia syndrome (PFS) is characterized by widespread chronic pain that affects the musculoskeletal system, fatigue, anxiety, sleep disturbance, headache and postural hypotension. The pathophysiology of PFS is unknown. The hypothalamic-pituitary-adrenal (HPA) axis seems to play an important role in PFS. Both hyperactivity and hypoactivity of the HPA axis have been reported in patients with PFS. In this study we assessed the HPA axis by 1 microg ACTH stimulation test and metyrapone test in 22 patients with PFS and in 15 age-, sex-, and body mass index (BMI)- matched controls. Metyrapone (30 mg/kg) was administered orally at 23:00 h and blood was sampled at 08:30 h the following morning for 11-deoxycortisol. ACTH stimulation test was carried out by using 1 microg (iv) ACTH as a bolus injection after an overnight fast, and blood samples were drawn at 0, 30 and 60 min. Peak cortisol level (659.4 +/- 207.2 nmol/l) was lower in the patients with PFS than peak cortisol level (838.7 +/- 129.6 nmol/l) in the control subjects (p < 0.05). Ten patients (45%) with PFS had peak cortisol responses to 1 microg ACTH test lower than the lowest peak cortisol detected in healthy controls. After metyrapone test 11-deoxycortisol level was 123.7 +/- 26 nmol/l in patients with PFS and 184.2 +/- 17.3 nmol/l in the controls (p < 0.05). Ninety five percent of the patients with PFS had lower 11-deoxycortisol level after metyrapone than the lowest 11-deoxycortisol level after metyrapone detected in healthy controls. We also compared the adrenal size of the patients with that of the healthy subjects and we found that the adrenal size between the groups was similar. This study clearly shows that HPA axis is underactivated in PFS, rather than overactivated.
J Endocrinol Invest. 2004 Jan;27(1):42-6
Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions?
OBJECTIVES: This study examines the concept of clinical endocannabinoid deficiency (CECD), and the prospect that it could underlie the pathophysiology of migraine, fibromyalgia, irritable bowel syndrome, and other functional conditions alleviated by clinical cannabis. METHODS: Available literature was reviewed, and literature searches pursued via the National Library of Medicine database and other resources. RESULTS: Migraine has numerous relationships to endocannabinoid function. Anandamide (AEA) potentiates 5-HT1A and inhibits 5-HT2A receptors supporting therapeutic efficacy in acute and preventive migraine treatment. Cannabinoids also demonstrate dopamine-blocking and anti-inflammatory effects. AEA is tonically active in the periaqueductal gray matter, a migraine generator. THC modulates glutamatergic neurotransmission via NMDA receptors. Fibromyalgia is now conceived as a central sensitization state with secondary hyperalgesia. Cannabinoids have similarly demonstrated the ability to block spinal, peripheral and gastrointestinal mechanisms that promote pain in headache, fibromyalgia, IBS and related disorders. The past and potential clinical utility of cannabis-based medicines in their treatment is discussed, as are further suggestions for experimental investigation of CECD via CSF examination and neuro-imaging. CONCLUSION: Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines.
Neuro Endocrinol Lett. 2004 Feb-Apr;25(1-2):31-9
Psychological stress and fibromyalgia: a review of the evidence suggesting a neuroendocrine link.
The present review attempts to reconcile the dichotomy that exists in the literature in relation to fibromyalgia, in that it is considered either a somatic response to psychological stress or a distinct organically based syndrome. Specifically, the hypothesis explored is that the link between chronic stress and the subsequent development of fibromyalgia can be explained by one or more abnormalities in neuroendocrine function. There are several such abnormalities recognised that both occur as a result of chronic stress and are observed in fibromyalgia. Whether such abnormalities have an aetiologic role remains uncertain but should be testable by well-designed prospective studies.
Arthritis Res Ther. 2004;6(3):98-106. Epub 2004 Apr 7
Neuroendocrine abnormalities in fibromyalgia.
Fibromyalgia is a disorder of unknown etiology characterized by chronic, widespread musculoskeletal pain and symptoms such as fatigue, poor sleep, gastrointestinal complaints, and psychologic problems that are similar to those experienced by patients with hormone deficiencies. This review summarizes the available data on the neuroendocrine function in fibromyalgia, including data on hormone secretion, circadian phase, and autonomic nervous system function. Studies suggest that there may be lower activity of a number of hypothalamic-pituitary-peripheral gland axes and altered autonomic nervous system function in patients with fibromyalgia. These reductions in activity are mild to moderate and do not result from alterations in circadian rhythms. The reduced hormonal and autonomic responses appear to reflect an impairment in the hypothalamic or central nervous system response to stimuli rather than a primary defect at the level of the pituitary gland or the peripheral glands. A combination of multiple, mild impaired responses may lead to more profound physiologic and clinical consequences as compared with a defect in only one system, and could contribute to the symptoms of fibromyalgia.
Curr Pain Headache Rep. 2002 Aug;6(4):289-98