Sympathetic nervous system function in fibromyalgia

Abstract:

This review focuses on studies of the sympathetic nervous system in fibromyalgia (FM). First, a brief review of the sympathetic system, and its relationship to the human stress response, is outlined. Then various studies of functional assessment of sympathetic function in FM are highlighted. Certain methods of assessment (eg, heart rate variability, biochemical, and psychophysical responses to various stressors) that we believe to be of specific importance for future research are discussed in greater detail. Finally, findings on autonomic function in related disorders–specifically, chronic fatigue syndrome, irritable bowel syndrome, and migraine–will be briefly presented.

 

Source: Petzke F, Clauw DJ. Sympathetic nervous system function in fibromyalgia. Curr Rheumatol Rep. 2000 Apr;2(2):116-23. http://www.ncbi.nlm.nih.gov/pubmed/11123048

 

The sympathetic nerve–an integrative interface between two supersystems: the brain and the immune system

Abstract:

The brain and the immune system are the two major adaptive systems of the body. During an immune response the brain and the immune system “talk to each other” and this process is essential for maintaining homeostasis. Two major pathway systems are involved in this cross-talk: the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). This overview focuses on the role of SNS in neuroimmune interactions, an area that has received much less attention than the role of HPA axis.

Evidence accumulated over the last 20 years suggests that norepinephrine (NE) fulfills the criteria for neurotransmitter/neuromodulator in lymphoid organs. Thus, primary and secondary lymphoid organs receive extensive sympathetic/noradrenergic innervation. Under stimulation, NE is released from the sympathetic nerve terminals in these organs, and the target immune cells express adrenoreceptors.

Through stimulation of these receptors, locally released NE, or circulating catecholamines such as epinephrine, affect lymphocyte traffic, circulation, and proliferation, and modulate cytokine production and the functional activity of different lymphoid cells. Although there exists substantial sympathetic innervation in the bone marrow, and particularly in the thymus and mucosal tissues, our knowledge about the effect of the sympathetic neural input on hematopoiesis, thymocyte development, and mucosal immunity is extremely modest.

In addition, recent evidence is discussed that NE and epinephrine, through stimulation of the beta(2)-adrenoreceptor-cAMP-protein kinase A pathway, inhibit the production of type 1/proinflammatory cytokines, such as interleukin (IL-12), tumor necrosis factor-alpha, and interferon-gamma by antigen-presenting cells and T helper (Th) 1 cells, whereas they stimulate the production of type 2/anti-inflammatory cytokines such as IL-10 and transforming growth factor-beta.

Through this mechanism, systemically, endogenous catecholamines may cause a selective suppression of Th1 responses and cellular immunity, and a Th2 shift toward dominance of humoral immunity. On the other hand, in certain local responses, and under certain conditions, catecholamines may actually boost regional immune responses, through induction of IL-1, tumor necrosis factor-alpha, and primarily IL-8 production.

Thus, the activation of SNS during an immune response might be aimed to localize the inflammatory response, through induction of neutrophil accumulation and stimulation of more specific humoral immune responses, although systemically it may suppress Th1 responses, and, thus protect the organism from the detrimental effects of proinflammatory cytokines and other products of activated macrophages.

The above-mentioned immunomodulatory effects of catecholamines and the role of SNS are also discussed in the context of their clinical implication in certain infections, major injury and sepsis, autoimmunity, chronic pain and fatigue syndromes, and tumor growth.

Finally, the pharmacological manipulation of the sympathetic-immune interface is reviewed with focus on new therapeutic strategies using selective alpha(2)- and beta(2)-adrenoreceptor agonists and antagonists and inhibitors of phosphodiesterase type IV in the treatment of experimental models of autoimmune diseases, fibromyalgia, and chronic fatigue syndrome.

 

Source: Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES. The sympathetic nerve–an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev. 2000 Dec;52(4):595-638. http://pharmrev.aspetjournals.org/content/52/4/595.long (Full article)

 

Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a poorly understood disease characterized by mental and physical fatigue, most often observed in young white females. Muscle pain at rest, exacerbated by exercise, is a common symptom. Although a specific defect in muscle metabolism has not been clearly defined, yet several studies report altered oxidative metabolism.

In this study, we detected oxidative damage to DNA and lipids in muscle specimens of CFS patients as compared to age-matched controls, as well as increased activity of the antioxidant enzymes catalase, glutathione peroxidase, and transferase, and increases in total glutathione plasma levels. From these results we hypothesize that in CFS there is oxidative stress in muscle, which results in an increase in antioxidant defenses.

Furthermore, in muscle membranes, fluidity and fatty acid composition are significantly different in specimens from CFS patients as compared to controls and to patients suffering from fibromyalgia. These data support an organic origin of CFS, in which muscle suffers oxidative damage.

 

Source: Fulle S, Mecocci P, Fanó G, Vecchiet I, Vecchini A, Racciotti D, Cherubini A, Pizzigallo E, Vecchiet L, Senin U, Beal MF. Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome. Free Radic Biol Med. 2000 Dec 15;29(12):1252-9. http://www.ncbi.nlm.nih.gov/pubmed/11118815

 

Results of isoproterenol tilt table testing in monozygotic twins discordant for chronic fatigue syndrome

Abstract:

BACKGROUND: The pathogenesis of chronic fatigue syndrome (CFS) is unknown. Neurally mediated hypotension (NMH) has been suggested as a common comorbid condition or a potential underlying cause.

METHODS: We conducted a cotwin control study of 21 monozygotic twins who were discordant for CFS. One twin met the 1994 Centers for Disease Control and Prevention criteria for CFS, and the other twin was healthy and denied chronic fatigue. The twins were selected from a volunteer twin registry in which at least 1 member reported persistent fatigue. As part of a 7-day clinical evaluation, all 21 twin pairs were evaluated with a 3-stage tilt table test with isoproterenol hydrochloride for the assessment of NMH. The presence of NMH was defined as syncope or presyncope associated with a decrease of 25 mm Hg in blood pressure and no associated increase in heart rate.

RESULTS: A positive tilt table test result was observed in 4 twins with CFS (19%) and in 4 healthy twins (19%). This difference was not statistically significant (matched pair odds ratio, 1.0; 95% confidence interval, 0.2-5.4; P>.90). Compared with the healthy twins, the twins with CFS reported more severe symptoms of CFS and NMH both in the week before and during the tilt table test.

CONCLUSIONS: These results do not support a major role for NMH in CFS. They highlight the importance of selecting well-matched control subjects, as well as the unique value of the monozygotic cotwin control design in the study of this illness. Arch Intern Med. 2000;160:3461-3468.

 

Source: Poole J, Herrell R, Ashton S, Goldberg J, Buchwald D. Results of isoproterenol tilt table testing in monozygotic twins discordant for chronic fatigue syndrome. Arch Intern Med. 2000 Dec 11-25;160(22):3461-8. http://www.ncbi.nlm.nih.gov/pubmed/11112240

 

Fatigue in chronic fatigue syndrome: a discourse analysis of women’s experiential narratives

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating condition. Approximately 75% of sufferers are women. The etiology of CFS is debated, but remains inconclusive. “Fatigue” is ill defined and conceptually problematic. The international multidisciplinary literature on CFS reveals a paucity of studies on women. Qualitative research to analyze women’s discourses on CFS is virtually absent.

Eleven New Zealand women of European descent with experience of CFS were interviewed in depth. Within the complex facets of CFS, this article reports specifically on an analysis of discourses on “fatigue.”

The predominant theme that emerged was that fatigue is articulated as “lack” or absence, which is not representable as an identifiable entity in biomedical terms. Parallels with chronic pain are briefly drawn. We conclude that approaches to CFS must respond to the diverse and complex constructions of the experience of fatigue evident in women’s narratives.

 

Source: Hart B, Grace VM. Fatigue in chronic fatigue syndrome: a discourse analysis of women’s experiential narratives. Health Care Women Int. 2000 Apr-May;21(3):187-201. http://www.ncbi.nlm.nih.gov/pubmed/11111465

 

Feminist perspectives on the social construction of chronic fatigue syndrome

Abstract:

We contrast Western medical views of chronic fatigue syndrome (CFS) etiology, diagnosis, and treatment with views maintained by a predominantly female CFS population. We argue that the failure of Western medicine to demonstrate a viral etiology for CFS led to a paradigmatic shift in research perspectives, which then embraced psychiatric and sociocultural explanations for CFS. As a result, CFS was delegitimized as a biomedical phenomenon within medical, academic, governmental, and public arenas.

We compare alternative social constructions of CFS with issues pertaining to multiple sclerosis (MS), an illness that similarly predominates among women. Patient perspectives suggest that the history of medical attitudes toward CFS may eventually parallel the transformations that occurred in relation to MS. In particular, the discovery of biological markers for CFS may lay to rest the categorization of CFS as largely within the psychiatric realm.

 

Source: Richman JA, Jason LA, Taylor RR, Jahn SC. Feminist perspectives on the social construction of chronic fatigue syndrome. Health Care Women Int. 2000 Apr-May;21(3):173-85. http://www.ncbi.nlm.nih.gov/pubmed/11111464

 

Chronic fatigue syndrome and depression

Comment on: Cerebral perfusion in chronic fatigue syndrome and depression. [Br J Psychiatry. 2000]

 

I found MacHale et al’s (2000) discussion of their results confusing. According to the abstract and methods, they screened their patients with chronic fatigue syndrome (CFS) to exclude those with depression. Then they examined this group further using a standardised psychiatric interview (Schedule for Affective Disorders and Schizophrenia), in order to “ exclude subjects with current psychiatric illness, with a particular emphasis on depression”. The data from the Hamilton Rating Scale for Depression are difficult to interpret given the number of illnessrated items, but the scores did not indicate a significant degree of depression either. So, having excluded “subjects with depression or anxiety”, why did the authors claim in their discussion that “the main limitation of the present study is that our CFS subjects had high levels of depression”?

You can read the rest of this comment here: http://bjp.rcpsych.org/content/177/5/470.long

 

Source: Goudsmit E. Chronic fatigue syndrome and depression. Br J Psychiatry. 2000 Nov;177:470. http://bjp.rcpsych.org/content/177/5/470.long

 

Controversies in neurological infectious diseases

Abstract:

The past several years have seen major advances in our understanding of neurological infectious diseases, their diagnosis, and their treatment. Along with these advances, however, new information about infectious agents and new therapeutic options have also introduced both uncertainty and controversy in the approach and management of patients with diseases of the central nervous system. Here, we discuss six such areas: the long-term efficacy of HAART therapy in treatment of HIV infection; the role of viral infection in chronic fatigue syndrome; Rasmussen’s encephalitis as an infectious or autoimmune disease; the spectrum of neurological diseases caused by rickettsial infection; the role of Mycoplasma pneumoniae in human central nervous system disease; and the possible association of Chlamydia pneumoniae and human herpesvirus 6 with multiple sclerosis.

 

Source: Greenlee JE, Rose JW. Controversies in neurological infectious diseases. Semin Neurol. 2000;20(3):375-86. http://www.ncbi.nlm.nih.gov/pubmed/11051301

 

Chronic fatigue syndrome and Australian psychiatry: lessons from the UK experience

Abstract:

OBJECTIVE: The aim of this paper is to outline the opportunities and dangers the chronic fatigue syndrome (CFS) issue presents to Australian psychiatry.

METHOD: The scientific literature of the last 50 years on CFS in adults was reviewed and samples of recent media portrayals of CFS in the UK and Australia were collected. The author has worked in both the UK and Australia managing adult CFS patients in specialist outpatient consultation-liaison (C-L) psychiatry settings.

RESULTS: Chronic fatigue syndrome has been at the heart of an acrimonious debate in the UK, both within the medical profession and in the wider community. UK psychiatry has been drawn into the debate, at times being the target of strong and potentially damaging criticism, yet UK psychiatry, especially the C-L subspecialty, has played a crucial role in clarifying appropriate research questions and in devising management strategies. The issue has served to enhance and broaden psychiatry’s perceived research and clinical role at the important medicine-psychiatry interface in that country.

CONCLUSIONS: Handled properly, the CFS issue offers Australian psychiatry, especially C-L psychiatry, an opportunity to make a useful contribution to patient care in a clinically difficult and contentious area, while at the same time serving to help broaden psychiatry’s scope in the Australian medical landscape.

 

Source: Couper J. Chronic fatigue syndrome and Australian psychiatry: lessons from the UK experience. Aust N Z J Psychiatry. 2000 Oct;34(5):762-9. http://www.ncbi.nlm.nih.gov/pubmed/11037362

 

Fatigue rating scales: an empirical comparison

Abstract:

BACKGROUND: There has been limited research comparing the efficacy of different fatigue rating scales for use with individuals with chronic fatigue syndrome (CFS). This investigation explored relationships between two commonly-used fatigue rating scales in CFS research, the Fatigue Scale and the Fatigue Severity Scale. Theoretically, these scales have been described as measuring different aspects of the fatigue construct. The Fatigue Scale was developed as a measure of the severity of specific fatigue-related symptoms, while the Fatigue Severity Scale was designed to assess functional outcomes related to fatigue.

METHODS: Associations of these scales with the eight definitional symptoms of CFS and with eight domains of functional disability were examined separately in: (1) an overall sample of individuals with a wide range of fatigue severity and symptomatology; (2) a subsample of individuals with CFS-like symptomatology, and, (3) a subsample of healthy controls.

RESULTS: Findings revealed that both scales are appropriate and useful measures of fatigue-related symptomatology and disability within a general population of individuals with varying levels of fatigue. However, the Fatigue Severity Scale appears to represent a more accurate and comprehensive measure of fatigue-related severity, symptomatology, and functional disability for individuals with CFS-like symptomatology.

 

Source: Taylor RR, Jason LA, Torres A. Fatigue rating scales: an empirical comparison. Psychol Med. 2000 Jul;30(4):849-56. http://www.ncbi.nlm.nih.gov/pubmed/11037093