Hypothalamic–Pituitary–Adrenal and Autonomic Nervous System Functioning in Fibromyalgia

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Response to stress: a coordinated neuroendocrine and autonomic nervous system event

In response to a stressful event, the neuroendocrine and autonomic nervous systems function in a coordinated fashion. For example, with a hypoglycemic stress that is induced by an injection of insulin, this response consists of increases in secretion of corticotropin, cortisol, growth hormone, pancreatic polypeptide, and glucagon and activation of the parasympathetic, sympathetic, and sympathoadrenal branches of the ANS. All of these responses together serve to increase blood sugar levels and

Hypothalamic–pituitary–adrenal axis: fatigue and pain

A critical component of the neuroendocrine response to stress is activation of the HPA axis. Individuals who have reduced HPA axis activity, such as those who are undergoing withdrawal from glucocorticoid therapy [50] or those who have Addison's disease [51], often have symptoms of fatigue, depressed mood, myalgias, and disturbed sleep. Unexplained fatigue also has been reported in individuals who have genetic alterations in HPA axis function, such as glucocorticoid receptor mutations that lead

Hypothalamic–pituitary–adrenal axis

Studies that assessed basal serum cortisol levels that were measured every 10 to 20 minutes for 24 to 40 hours [12], [13], cortisol binding globulin levels [14], [16], and 24-hour urinary free cortisol levels [14], [15] showed normal HPA axis functioning in fibromyalgia. Reduced 24-hour urinary free cortisol levels were reported under ambulatory conditions in individuals with fibromyalgia [16], [17], [18]. In addition, direct stimulation of the adrenal with corticotropin [14], [18] or

Neuroendocrine and autonomic nervous system response to stress

The neuroendocrine and sympathoadrenal response to stress were examined in individuals who had fibromyalgia. Administration of a controlled hypoglycemic stimulus, using a graded hypoglycemic-hyperinsulinemic clamp technique (glucose was decreased from 90 mg/dL to 40 mg/dL by 10 mg/dL every 30 minutes), showed significant (∼30%) decreases in the corticotropin and epinephrine responses to hypoglycemia in premenopausal women who had fibromyalgia [14]. Furthermore, fibromyalgia symptoms, as

The origin of changed stress responsiveness

A major dilemma exists in interpreting the source of altered ANS and HPA stress responsiveness [11], [75]. It may reflect an impairment that is constitutional or acquired by being exposed to severe trauma in the past; however, it also is possible that reduced stress responsiveness reflects the current consequences of stress, low physical fitness, sleep disturbance, or pain. Fig. 1 presents a model for understanding the possible interactions between stress, the stress response, and symptoms of

Treatment

Treatments for fibromyalgia attempt to deal with the symptoms of fibromyalgia and the physical and psychosocial consequences of the disorder. Pharmacologic interventions, physical exercise, and cognitive-behavioral therapy are used; however, a uniform and satisfactory treatment strategy for fibromyalgia is not known. This is due, in part, to our lack of understanding of the underlying pathophysiology of this disorder. If reductions in neuroendocrine and ANS stress responsiveness were important

Summary

The small numbers of studies that have examined coordinated HPA axis and ANS functioning in fibromyalgia showed hyporeactivity to applied stress. This altered neuroendocrine responsiveness seems to be due to changes in hypothalamic function, not to a primary adrenal defect. It is unknown whether these neuroendocrine alterations are involved in the pathophysiology of fibromyalgia and contribute to its ongoing symptomatology or are a consequence of pain and its associated symptoms (eg, fatigue,

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    • Blunted short-term autonomic cardiovascular reactivity to orthostatic and clinostatic challenges in fibromyalgia as an indicator of the severity of chronic pain

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      Accordingly, our study did not replicate the previously observed greater HR in FM sufferers at rest (Cohen et al., 2001; Furlan et al., 2005; Reyes del Paso et al., 2010, 2011; Thieme et al., 2006), and challenges the idea of sympathetic overactivity in the disorder (Martinez-Lavin, 2007). In this sense, the study confirms the hypothesis that autonomic abnormalities may mainly be detected in response to stressors (Adler and Geenen, 2005; Pardo et al., 2019). Previously, CPAST has been successfully applied to patients with different chronic pain conditions, and to healthy individuals, for evaluating relationships of pain severity and negative and positive moods with stress-related autonomic reactivity; more blunted reactivity was observed in those with more severe pain and negative moods (Davydov and Czabak-Garbacz, 2017; Davydov and Perlo, 2015).

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