Increased Neural Sympathetic Activation in Fibromyalgia Syndrome

Abstract:  Fibromyalgia (FM) is a syndrome characterized by widespread musculoskeletal pain, although the mechanisms underlying the pain have not been fully elucidated. FM patients describe a number of nonspecific symptoms, such as anxiety, depression, fatigue, unrefreshing sleep, and gastrointestinal complaints, which appear after a flu‐like illness, or after physical or emotional trauma in half of the patients, and are often exacerbated by exertion, stress, lack of sleep, and weather changes. There may also be symptoms of orthostatic intolerance, which suggests underlying abnormalities in cardiovascular neural regulation. Research suggests that various components of the central nervous system are involved, including the hypothalamic‐pituitary‐adrenal (HPA) axis, pain‐processing pathways, and the autonomic nervous system (ANS). This review discusses the general aspects of the altered HPA and ANS, sympathetic overactivity, and alterations in cardiovascular autonomic responses to gravitational stimuli.

[1]  J. Trinder,et al.  Autonomic activity during human sleep as a function of time and sleep stage , 2001, Journal of sleep research.

[2]  R. Geenen,et al.  Hypothalamic-pituitary-adrenal and autonomic nervous system functioning in fibromyalgia. , 2005, Rheumatic diseases clinics of North America.

[3]  H. Calkins,et al.  Provocation of hypotension and pain during upright tilt table testing in adults with fibromyalgia. , 1997, Clinical and experimental rheumatology.

[4]  J. Shaver,et al.  Decreased nocturnal levels of prolactin and growth hormone in women with fibromyalgia. , 2001, The Journal of clinical endocrinology and metabolism.

[5]  I. Russell,et al.  Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome. , 1992, The Journal of rheumatology.

[6]  D. Wasserman,et al.  Effects of gender on neuroendocrine and metabolic counterregulatory responses to exercise in normal man. , 2000, The Journal of clinical endocrinology and metabolism.

[7]  J L Andreassi,et al.  Effects of stress management on blood pressure and other cardiovascular variables. , 1991, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[8]  G. Alarcón,et al.  Current concepts in the pathophysiology of abnormal pain perception in fibromyalgia. , 1998, The American journal of the medical sciences.

[9]  K. Jones,et al.  Glucocorticoids: potent inhibitors and stimulators of growth hormone secretion. , 1990, Endocrinology.

[10]  P. Dessein,et al.  Neuroendocrine deficiency-mediated development and persistence of pain in fibromyalgia: a promising paradigm? , 2000, Pain.

[11]  J. B. Baena Díez,et al.  [Reflex sympathetic dystrophy]. , 2008, Medicina clinica.

[12]  G. Neeck,et al.  Thyroid function in patients with fibromyalgia syndrome. , 1992, The Journal of rheumatology.

[13]  D. J. Claliw.  The pathogenesis of chronic pain and fatigue syndromes, with special reference to fibromyalgia , 1995 .

[14]  R. Bennett,et al.  A randomized, double-blind, placebo-controlled study of growth hormone in the treatment of fibromyalgia. , 1998, The American journal of medicine.

[15]  L Neumann,et al.  Autonomic dysfunction in patients with fibromyalgia: application of power spectral analysis of heart rate variability. , 2000, Seminars in arthritis and rheumatism.

[16]  H. Fields,et al.  Causalgia and reflex sympathetic dystrophy: Does the sympathetic nervous system contribute to the generation of pain? , 1999, Muscle & nerve.

[17]  W. Hopman,et al.  Dysautonomia among patients with fibromyalgia: a noninvasive assessment. , 2000, The Journal of rheumatology.

[18]  R Furlan,et al.  Chronic orthostatic intolerance: a disorder with discordant cardiac and vascular sympathetic control. , 1998, Circulation.

[19]  Kenzo Hirao,et al.  Correlation between electroencephalography and heart rate variability during sleep , 2003, Psychiatry and clinical neurosciences.

[20]  B. Wallin,et al.  Do patients with primary fibromyalgia have an altered muscle sympathetic nerve activity? , 1992, Pain.

[21]  M. Martínez-Lavín.  Fibromyalgia as a sympathetically maintained pain syndrome , 2004, Current pain and headache reports.

[22]  E. C. Dawson,et al.  Follicular phase hypothalamic-pituitary-gonadal axis function in women with fibromyalgia and chronic fatigue syndrome. , 2000, The Journal of rheumatology.

[23]  R. Goldsmith,et al.  Exercise and autonomic function , 2000, Coronary artery disease.

[24]  B. Bengtsson,et al.  Low growth hormone secretion in patients with fibromyalgia--a preliminary report on 10 patients and 10 controls. , 1998, The Journal of rheumatology.

[25]  J E Michalek,et al.  Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome. , 1994, Arthritis and rheumatism.

[26]  William R Lariviere,et al.  The role of corticotropin-releasing factor in pain and analgesia , 2000, Pain.

[27]  G. Adler,et al.  Growth hormone and insulin-like growth factor-1 concentrations in women with fibromyalgia. , 2003, The Journal of rheumatology.

[28]  A. Porta,et al.  Abnormalities of cardiovascular neural control and reduced orthostatic tolerance in patients with primary fibromyalgia. , 2005, The Journal of rheumatology.

[29]  P. L. Munson.  Adrenal Cortex , 1951, British medical journal.

[30]  D. Clauw.  The pathogenesis of chronic pain and fatigue syndromes, with special reference to fibromyalgia. , 1995, Medical hypotheses.

[31]  B. van Houdenhove,et al.  Fibromyalgia: A Stress Disorder? , 2004, Psychotherapy and Psychosomatics.

[32]  D. Goldenberg.  Do infections trigger fibromyalgia? , 1993, Arthritis and rheumatism.

[33]  A. Bengtsson,et al.  Skeletal muscle function in primary fibromyalgia. Effect of regional sympathetic blockade with guanethidine , 1988, Acta neurologica Scandinavica.

[34]  D. Buskila,et al.  Neuroendocrine mechanisms in fibromyalgia-chronic fatigue. , 2001, Best practice & research. Clinical rheumatology.

[35]  Birgitta Berglund,et al.  Quantitative and qualitative perceptual analysis of cold dysesthesia and hyperalgesia in fibromyalgia , 2002, Pain.

[36]  G. Littlejohn,et al.  Pressure pain threshold in pain-free subjects, in patients with chronic regional pain syndromes, and in patients with fibromyalgia syndrome. , 1993, Arthritis and rheumatism.

[37]  F. Wolfe,et al.  The prevalence and characteristics of fibromyalgia in the general population. , 1995, Arthritis and rheumatism.

[38]  C. Pineda,et al.  Orthostatic sympathetic derangement in subjects with fibromyalgia. , 1997, The Journal of rheumatology.

[39]  C. Tsigos,et al.  Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. , 2002, Journal of psychosomatic research.

[40]  M. Martínez-Lavín.  Management of dysautonomia in fibromyalgia. , 2002, Rheumatic diseases clinics of North America.

[41]  M. Demitrack,et al.  Evidence for and Pathophysiologic Implications of Hypothalamic‐Pituitary‐Adrenal Axis Dysregulation in Fibromyalgia and Chronic Fatigue Syndrome , 1998, Annals of the New York Academy of Sciences.

[42]  G. Chrousos,et al.  Syndromes of Glucocorticoid Resistance , 1993, Annals of Internal Medicine.

[43]  E. D. de Kloet,et al.  Altered reactivity of the hypothalamic-pituitary-adrenal axis in the primary fibromyalgia syndrome. , 1993, The Journal of rheumatology.

[44]  V. Somers,et al.  Chronic orthostatic intolerance: part of a spectrum of dysfunction in orthostatic cardiovascular homeostasis? , 1998, Circulation.

[45]  W. Müller,et al.  Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome. , 1993, The Journal of rheumatology.

[46]  P. Tugwell,et al.  The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. , 1990, Arthritis and rheumatism.

[47]  R M Bennett,et al.  Hypothalamic-pituitary-insulin-like growth factor-I axis dysfunction in patients with fibromyalgia. , 1997, The Journal of rheumatology.

[48]  R. Bennett,et al.  A double blind crossover trial of prednisone versus placebo in the treatment of fibrositis. , 1985, The Journal of rheumatology.

[49]  R. Bennett,et al.  Low levels of somatomedin C in patients with the fibromyalgia syndrome. A possible link between sleep and muscle pain. , 1992, Arthritis and rheumatism.

[50]  J. Gustafsson,et al.  Primary cortisol resistance associated with a thermolabile glucocorticoid receptor in a patient with fatigue as the only symptom. , 1986, The Journal of clinical investigation.

[51]  G. Chrousos,et al.  Corticosteroid therapy, nonendocrine disease, and corticosteroid withdrawal. , 1997, Current therapy in endocrinology and metabolism.

[52]  B. Kudielka,et al.  Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis. , 1999, Psychosomatic medicine.

[53]  M. Soto,et al.  Circadian studies of autonomic nervous balance in patients with fibromyalgia: a heart rate variability analysis. , 1998, Arthritis and rheumatism.