Abnormalities of cardiovascular neural control and reduced orthostatic tolerance in patients with primary fibromyalgia. Abnormalities of cardiovascular neural control and reduced orthostatic tolerance in patients with primary fibromyalgia.
J Rheumatol. 2005 Sep;32(9):1787-93
Authors: Furlan R, Colombo S, Perego F, Atzeni F, Diana A, Barbic F, Porta A, Pace F, Malliani A, Sarzi-Puttini P
OBJECTIVE: Fibromyalgia (FM) is a syndrome characterized by widespread musculoskeletal pain. Symptoms of orthostatic intolerance may also be present, suggesting underlying abnormalities of cardiovascular neural regulation. We tested the hypothesis that FM is characterized by sympathetic overactivity and alterations in cardiovascular autonomic response to gravitational stimulus. METHODS: Sixteen patients with primary FM and 16 healthy controls underwent electrocardiography examination, finger blood pressure, respiration, and muscle sympathetic nerve activity (MSNA) recordings at rest and during stepwise tilt test, up to 75 degrees . The autonomic profile was assessed by MSNA, plasma catecholamine, and spectral indices of cardiac sympathetic (LFRR in normalized units, NU) and vagal (HFRR both in absolute and NU) modulation and of sympathetic vasomotor control (LFSAP) computed by spectrum analysis of RR and systolic arterial pressure (SAP) variability. Arterial baroreflex function was evaluated by the SAP/RR spontaneous-sequences technique, the index a, and the gain of MSNA/diastolic pressure relationship during stepwise tilt test. RESULTS: At rest, patients showed higher values of heart rate, MSNA, LFRR NU, LF/HF, LFSAP, and reduced HFRR than controls. During tilt test, lack of increase of MSNA, less decrease of HFRR, and excessive rate (44%) of syncope were found in patients, suggesting reduced capability to enhance the sympathetic activity to vessels and withdraw the vagal modulation to sino-atrial node. Baroreflex function was similar in both groups. CONCLUSION: Patients with FM have an overall enhancement of cardiovascular sympathetic activity while recumbent. Lack of increased sympathetic discharge to vessels and decreased cardiac vagal activity characterize their autonomic profile during tilt test, and might account for the excessive rate of syncope.
PMID: 16142879 [PubMed - indexed for MEDLINE]
Furlan R, Colombo S, Perego F, Atzeni F, Diana A, Barbic F, Porta A, Pace F, Malliani A, Sarzi-Puttini P
Therapeutic and preventive interventions for postulated vasoactive neuropeptide autoimmune fatigue-related disorders. Therapeutic and preventive interventions for postulated vasoactive neuropeptide autoimmune fatigue-related disorders.
Med Hypotheses. 2005;65(4):797-803
Authors: Staines DR
Major advances have been made in understanding the relatively novel group of vasoactive (vasodilatory) neuropeptides (VNs) in humans. VNs comprise a novel but expanding group of substances having immunoregulation, inflammation modulation, neurotransmitter, neurotrophic, hormonal and metabolic functions. These substances may control gene expression for mRNA for themselves and their receptors. They have complex relationships with gaseous and other neurotransmitters and xenobiotic substances. Theoretical arguments have implicated these substances in autoimmune phenomena resulting in fatigue-related conditions such as chronic fatigue syndrome (CFS), sudden infant death syndrome (SIDS), fibromyalgia (FM) and Gulf War syndrome (GWS) but remain unproven. As well as possibly spontaneous onset, the precipitating causes of VN autoimmune dysfunction are likely to be a combination of genetic predisposition, infection and xenobiotic substances. Therapeutic and preventive possibilities for postulated VN autoimmune conditions will be influenced by the complex patholophysiology underpinning them. Some speculative possibilities are VN substitution/replacement, preservation of biological effect, epigenetic DNA modifications, plasma exchange, anti-cholinesterases, e.g., pyridostigmine, corticosteroids and other drug treatments, thymectomy, intravenous immunoglobulin and anti-idiotype antibodies, and CpG/DNA vaccines. Prevention and treatment of possible VN autoimmune fatigue-related disorders may prove to be important areas for future research and development.
PMID: 16042995 [PubMed - in process]
Staines DR
Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment. Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment.
J Rheumatol Suppl. 2005 Aug;75:6-21
Authors: Mease P
Fibromyalgia syndrome (FM) is a common chronic pain condition that affects at least 2% of the adult population in the USA and other regions in the world where FM is studied. Prevalence rates in some regions have not been ascertained and may be influenced by differences in cultural norms regarding the definition and attribution of chronic pain states. Chronic, widespread pain is the defining feature of FM, but patients may also exhibit a range of other symptoms, including sleep disturbance, fatigue, irritable bowel syndrome, headache, and mood disorders. Although the etiology of FM is not completely understood, the syndrome is thought to arise from influencing factors such as stress, medical illness, and a variety of pain conditions in some, but not all patients, in conjunction with a variety of neurotransmitter and neuroendocrine disturbances. These include reduced levels of biogenic amines, increased concentrations of excitatory neurotransmitters, including substance P, and dysregulation of the hypothalamic-pituitary-adrenal axis. A unifying hypothesis is that FM results from sensitization of the central nervous system. Establishing diagnosis and evaluating effects of therapy in patients with FM may be difficult because of the multifaceted nature of the syndrome and overlap with other chronically painful conditions. Diagnostic criteria, originally developed for research purposes, have aided our understanding of this patient population in both research and clinical settings, but need further refinement as our knowledge about chronic widespread pain evolves. Outcome measures, borrowed from clinical research in pain, rheumatology, neurology, and psychiatry, are able to distinguish treatment response in specific symptom domains. Further work is necessary to validate these measures in FM. In addition, work is under way to develop composite response criteria, intended to address the multidimensional nature of this syndrome. A range of medical treatments, including antidepressants, opioids, nonsteroidal antiinflammatory drugs, sedatives, muscle relaxants, and antiepileptics, have been used to treat FM. Nonpharmaceutical treatment modalities, including exercise, physical therapy, massage, acupuncture, and cognitive behavioral therapy, can be helpful. Few of these approaches have been demonstrated to have clear-cut benefits in randomized controlled trials. However, there is now increased interest as more effective treatments are developed and our ability to accurately measure effect of treatment has improved. The multifaceted nature of FM suggests that multimodal individualized treatment programs may be necessary to achieve optimal outcomes in patients with this syndrome.
PMID: 16078356 [PubMed - indexed for MEDLINE]
Mease P
Magnesium depletion with hypo- or hyper- function of the biological clock may be involved in chronopathological forms of asthma. Magnesium depletion with hypo- or hyper- function of the biological clock may be involved in chronopathological forms of asthma.
Magnes Res. 2005 Mar;18(1):19-34
Authors: Durlach J, Pagès N, Bac P, Bara M, Guiet-Bara A
Asthma is a chronic, inflammatory disorder of the airways leading to airflow limitation. Its worldwide rise, mainly in developed countries, is a matter of concern. Nocturnal asthma (NA) frequently occurs and concerns two thirds of asthmatics. But, it remains controversial whether NA is a distinct entity or is a manifestation of more severe asthma. Generally, it is considered as an exacerbation of the underlying pathology. The pathological mechanisms most likely involve endogenous circadian rhythms with pathological consequences on both respiratory inflammation and hyperresponsiveness. A decrease in blood and tissue magnesium levels is frequently reported in asthma and often testifies to a true magnesium depletion. The link with magnesium status and chronobiology are well established. The quality of magnesium status directly influences the Biological Clock (BC) function, represented by the suprachiasmatic nuclei and the pineal gland. Conversely, BC dysrythmias influence the magnesium status. Two types of magnesium deficits must be clearly distinguished: deficiency corresponding to an insufficient intake which can be corrected through mere nutritional Mg supplementation and depletion due to a dysregulation of the magnesium status which cannot be corrected through nutritional supplementation only, but requires the more or less specific correction of the dysregulation mechanisms. Both in clinical and in animal experiments, the dysregulation mechanisms of magnesium depletion associate a reduced magnesium intake with various types of stress including biological clock dysrhythmias. The differenciation between Mg depletion forms with hyperfunction of BC (HBC) and forms with hypofunction of BC (hBC) is seminal and the main biological marker is melatonin (MT) production alteration. We hypothesize that magnesium depletion with HBC or hBC may be involved in chronopathological forms of asthma. Nocturnal asthma would be linked to HBC, represented by an increase in MT levels. The corresponding clinical forms associate diverse expressions of nervous hypoexcitability such as depression, cluster headaches, dyssomnia, mainly advanced sleep phase syndrome, some clinical forms of chronic fatigue syndrome and of fibromyalgia. The main comorbidities are depression and/or asthenia. They take place during the night or the "bad" seasons (autumn and winter) when sunshine is at a minimum. The corresponding chronopathological therapy relies on bright light phototherapy sometimes with additional psychoanaleptics. Conversely, asthma forms linked to hBC are less frequently studied as a whole and present a decrease in MT levels. They associate various signs of nervous hyperexcitability such as anxiety, diurnal cephalalgia (mainly migraine), dyssomnia, mainly delayed sleep phase syndrome, and some clinical forms of chronic fatigue syndrome and of fibromyalgia. The treatment relies on diverse forms of "darkness therapy", possibly with the help of some psycholeptics. Finally, the treatment of asthma involves the maintenance of a standard dosing schedule of anti-asthma drugs, a balanced magnesium intake and the appropriate treatment of the chronopathological disorders.
PMID: 15945613 [PubMed - indexed for MEDLINE]
Durlach J, Pag s N, Bac P, Bara M, Guiet-Bara A
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