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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the first comprehensive description of the symptoms of FMS by Yunus et al (1981), numerous investigations have confirmed that FMS is a clinical entity. However, the aetiology of the syndrome is still not fully elucidated. It seems, however, logical to place the origin of the disorder in the muscle. Muscle pain, especially at the muscle-tendon junctions, fatigue and stiffness are the first symptoms. A malfunction of energy metabolism has been detected in part of the muscle fibres. However, it has to be considered that the muscle is not an isolated entity. Its activity is controlled by segmentally arranged motor units of the ventral horn of the spinal cord in response to proprioceptive afferent signals arising in the muscle spindles or in other sensory elements including nociceptors. Together with supraspinal descending inputs, the spinal motor neurone pool is the common final pathway for segmental and suprasegmental inputs, making the motor system extremely powerful for adaptive adjustments but also vulnerable if deficits occur in either of these input levels. A second, recently discovered abnormality seen in FMS is a lowered serotonin level in peripheral and most likely also central structures. The underlying mechanism seems to be defective absorption of the precursor amino acid tryptophan from the gut. Serotonin is involved centrally in the regulation of the sleep pattern, and at the spinal level it acts as a 'gain setter' of motoneurone excitability and suppresses signal transmission of noxious stimuli in dorsal horn neurones. Either of these two disturbances, muscle energy depletion or serotonin deficiency, could by itself evoke many of the symptoms of FMS, and their combined appearance will perpetuate the disease. Depressed levels of somatomedin C, caused by a deficit of stage 4 sleep-dependent release of GH, might represent an additional factor in preventing proper development or repair of myoskeletal structures. Malabsorption of certain amino acids, possibly due to a genetic disorder of gut transport mechanisms, may constitute an additional deleterious factor. The abnormalities found in the HPA and HPT axis may be seen as an attempt of the organism to restore homeostasis. The stimulus eliciting this counter-regulatory reaction may be pain or other afferent signals which normally do not reach the central nervous system. It is doubtful whether the unspecific activation of the HPA axis in a non-inflammatory disease is beneficial.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuromediator and hormonal perturbations in fibromyalgia syndrome: results of chronic stress? 785 Aug 79

We discussed mainly neurochemical etiology of affective disorders (A.D.). Neurochemically, decreased 5-HT uptake in the platelet, increased 5-HT2 receptor in the platelet and cortex of suicides, increased beta receptor in the brains of suicide, functional abnormality of alpha 2 receptor in clonidine, DMI test, GABAB receptor up-regulation after chronic administration of antidepressants and mood stabilizers, participation of neuropeptide Y, and abnormality of HPA axis were recognized. Moreover, we referred to the importance of psychosocial and genetic factors. As for the etiology of A.D., while predisposition and environment participate, the method of participation will be different in subtypes. Frailty to stress in a broad sense, however is commonly seen in A.D. Though psychosocial factors are important, the physical condition, which involves fatigue, cannot be ignored. And, it is the most important that the biological and genetical factors which cause A.D., in the face of stimuli, must first be elucidated.
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PMID:[Etiology of affective disorders]. 791 50

Hypercortisolism in depression seems to preferentially reflect activation of hypothalamic CRH secretion. Although it has been postulated that this hypercortisolism is an epiphenomenon of the pain and stress of major depression, our data showing preferential participation of AVP in the hypercortisolism of chronic inflammatory disease suggest specificity for the pathophysiology of hypercortisolism in depression. Our findings that imipramine causes a down-regulation of the HPA axis in experimental animals and healthy controls support an intrinsic role for CRH in the pathophysiology of melancholia and in the mechanism of action of psychotropic agents. Our data suggest that hypercortisolism is not the only form of HPA dysregulation in major depression. In a series of studies, commencing in patients with Cushing's disease, and extending to hyperimmune fatigue states such as chronic fatigue syndrome and examples of atypical depression such as seasonal affective disorder, we have advanced data suggesting hypofunction of hypothalamic CRH neurons. These data raise the question that the hyperphagia, hypersomnia, and fatigue associated with syndromes of atypical depression could reflect a central deficiency of a potent arousal-producing anorexogenic neuropeptide. In the light of data presented elsewhere in this symposium regarding the role of a hypofunctioning hypothalamic CRH neuron in susceptibility to inflammatory disease, these data also raise the question of a common pathophysiological mechanism in syndromes associated both with inflammatory manifestations and atypical depressive symptoms. This concept of hypofunctioning of hypothalamic CRH neurons in these disorders also raises the question of novel forms of neuropharmacological intervention in both inflammatory diseases and atypical depressive syndromes.
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PMID:Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs. 859 44

The stress system is controlled by brain nuclei at the hypothalamus and brainstem. These nuclei interact with each other and control the HPA axis and sympathetic nervous systems, respectively. Major inputs to the stress system arise from the cerebral cortex and subcortical systems, the sensory organs and nerves, and the endocrine and immune systems. The major peripheral effectors of the stress system are glucocorticoids and the catecholamines. Pathological hypoactivity of the stress system has been associated with atypical depression, the chronic fatigue/fibromyalgia syndromes and autoimmune inflammatory disease; hyperactivity with melancholic depression and anxiety disorders. The stress system responds in a quantitatively and qualitatively specific fashion to different stressors. A major role of the HPA axis is to restrain the immune system and prevent tissue damage. Reciprocal interactions between the HPA axis and immune system constitutes a new endocrine feedback loop that has given rise to the field of neuroendocrine immunology. Gonadal axis hormones directly, and indirectly via the HPA axis, alter the tone of the immune system and the quality and quantity of the inflammatory responses. Effects of the HPA axis on the gonadal axis are consistent with conservation and redirection of valuable resources towards homeostasis during times of stress. These complex interactions between the HPA axis, immune and the gonadal systems may prove to be fundamental in the genesis and perpetuation of autoimmune disease.
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PMID:The three-way interactions between the hypothalamic-pituitary-adrenal and gonadal axes and the immune system. 891 46

Fibromyalgia (FM) falls into the spectrum of what might be termed 'stress-associated syndromes' by virtue of frequent onset after acute or chronic stressors and apparent exacerbation of symptoms during periods of physical or emotional stress. Patients with FM exhibit disturbances of the major stress-response systems, the HPA axis and the sympathetic nervous system. Integrated basal cortisol levels measured by 24-hour urine-free cortisol are low. FM patients display a unique pattern of HPA axis perturbation characterized by exaggerated ACTH response to exogenous CRH or to endogenous activators of CRH such as insulin-induced hypoglycaemia. The cortisol response to increased ACTH in these stress paradigms is blunted, as is the the cortisol response to exercise. Functional analysis suggests that FM patients may also exhibit disturbed autonomic system activity. For example, plasma NPY, a peptide co-localized with norepinephrine in the sympathetic nervous system, is low in patients with FM. Abnormalities of related neuronal systems, particularly decreased serotonergic activity, may contribute to the observed neuroendocrine perturbations in FM. Finally, other neuroendocrine systems, including the growth hormone axis, are also abnormal in FM patients. Many clinical features of FM and related disorders, such as widespread pain and fatigue, could be related to the observed neuroendocrine perturbations. This hypothesis is supported by the observation that many useful treatments for FM affect the function of these central nervous system centres. Further clarification of the role of neuroendocrine abnormalities in patients with FM, and the relationship of these disturbances with particular symptoms, may lead to improved therapeutic strategies.
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PMID:Neurohormonal perturbations in fibromyalgia. 891 54

HPA axis abnormalities in FM, CFS, and other stress-related disorders must be placed in a broad clinical context. We know that interventions providing symptomatic improvement in patients with FM and CFS can directly or indirectly affect the HPA axis. These interventions include exercise, tricyclic anti-depressants, and serotonin reuptake inhibitors. There is little direct information as to how the specific HPA axis perturbations seen in FM can be related to the major symptomatic manifestations of pain, fatigue, sleep disturbance, and psychological distress. Since many of these somatic and psychological symptoms are present in other syndromes that exhibit HPA axis disturbances, it seems reasonable to suggest that there may be some relationship between basal and dynamic function of the HPA axis and clinical manifestations of FM and CFS.
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PMID:The hypothalamic-pituitary-adrenal stress axis in fibromyalgia and chronic fatigue syndrome. 1002 87

Just as our caveman forebears were frail in the face of predatory animals, we are frail in today's society of childhood neglect or abuse, bumper-to-bumper traffic, frustration at work, and multiple daily hassles. The same neuroendocrine systems and pain regulatory mechanisms that protected early man during acute stress are still encoded in our genome, but may be maladaptive in psychologically and physiologically vulnerable people faced with chronic stress. Many patients with fibromyalgia become vulnerable because of the long-lasting psychological and neurophysiological effects of negative experiences in childhood. Ill-equipped with positive cognitive, emotional, and behavioral skills as adults, they display maladaptive coping strategies, low self-efficacy, and negative mood when confronted with the inevitable stressors of life. Psychological distress ensues, which reduces thresholds for pain perception and tolerance (already relatively low in women) even further. Converging lines of psychological and neurobiological evidence strongly suggest that chronic stress-related blunting of the HPA, sympathetic, and other axes of the stress response together with associated alterations in pain regulatory mechanisms may finally explain the pain and fatigue of fibromyalgia. Vulnerable people who can be classified by the ACR criteria as having fibromyalgia do not have a discrete disease. They are simply the most ill in a continuum of distress, chronic pain, and painful tender points in the general population.
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PMID:Pain in fibromyalgia. 1008 59

This study examined the presence of hypersensitivity to dental and environmental metals in patients with clinical disorders complicated with chronic fatigue syndrome. Three groups of patients were examined through medical history, dental examination, and by using a modified test of blast transformation for metals-MELISA(R). The three groups consisted of the following: 22 patients with autoimmune thyroiditis with or without polyglandular autoimmune activation; 28 fatigued patients free from endocrinopathy; and 22 fatigued professionals without evidence of autoimmunity. As controls, a population sample or 13 healthy subjects without any evidence of metal sensitivity was included. Healthy controls did not complain of marked fatigue and their laboratory tests did not show signs of autoimmunity and endocrinopathy. We have found that fatigue, regardless of the underlying disease, is primarily associated with hypersensitivity to inorganic mercury and nickel. The lymphocyte stimulation by other metals was similar in fatigued and control groups. To evaluate clinical relevance of positive in vitro findings, the replacement of amalgam with metal-free restorations was performed in some of the patients. At a six-month follow-up, patients reported considerably alleviated fatigue and disappearance of many symptoms previously encountered; in parallel, lymphocyte responses to metals decreased as well. We suggest that metal-driven inflammation may affect the hypothalamic-pituitary-adrenal axis (HPA axis) and indirectly trigger psychosomatic multisymptoms characterizing chronic fatigue syndrome, fibromyalgia, and other diseases of unknown etiology.
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PMID:Mercury and nickel allergy: risk factors in fatigue and autoimmunity. 1146 17

Sleep is an important component of mammalian homeostasis, vital for survival. Sleep disorders are common in the general population and are associated with significant medical, psychologic, and social disturbances. Sleep, in particular deep sleep, has an inhibitory influence on the HPA axis, whereas activation of the HPA axis or administration of glucocorticoids can lead to arousal and sleeplessness. Insomnia, the most common sleep disorder, is associated with a 24-hour increase of ACTH and cortisol secretion, consistent with a disorder of central nervous system hyperarousal. Sleepiness and fatigue are very prevalent in the general population, and recent studies have demonstrated that the proinflammatory cytokines IL-6 and/or TNF-alpha are elevated in disorders associated with excessive daytime sleepiness, such as sleep apnea, narcolepsy, and idiopathic hypersomnia. Sleep deprivation leads to sleepiness and daytime hypersecretion of IL-6. Combined, these findings suggest that the HPA axis stimulates arousal, while IL-6 and TNF-alpha are possible mediators of excessive daytime sleepiness in humans.
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PMID:Sleep, the hypothalamic-pituitary-adrenal axis, and cytokines: multiple interactions and disturbances in sleep disorders. 1205 86

Fatigue is often related to cancer, and that related to its treatment is the most commonly reported side effect of cancer treatment. It differs from that induced by other causes, such as sleep disturbance and exertion, as the latter are typically alleviated by a period of rest. In contrast to exercise-induced fatigue, the fatigue reported by cancer patients is usually described as an unusual, excessive, whole-body experience that is disproportionate or unrelated to activity or exertion and is not relieved by rest or sleep. Cancer-related fatigue is a subjective experience that has a clear detrimental effect on a cancer patient's quality of life and ability to sustain the usual personal, professional, and social relationships. The fatigue can be pervasive: cancer patients frequently report that fatigue begins with treatment, continues during the course of chemotherapy or radiation treatment, and declines somewhat - but frequently sustains at a higher-than-baseline rate - after treatment is over. It may also persist for several years even in patients with no apparent disease. While a number of researchers have speculated about the nature of cancer-related fatigue, there has been little systematic research on its etiology or treatment. In many aspects our knowledge of the fatigue mechanisms in cancer patients is at a similar stage to that reached in our understanding of anti-cancer therapy-induced nausea and vomiting about 20 years ago. This paper introduces four plausible hypotheses for the development of fatigue. Evidence available to support a role for anemia, adenosine triphosphate, vagal afferents, and the interaction of the HPA/cytokines and 5HT is discussed.
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PMID:Fatigue associated with cancer and its treatment. 1213 22


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