Function In Fibromyalgia Research Articles

Using fMRI to evaluate the effects of milnacipran on central pain processing in patients with fibromyalgia

BackgroundIn recent years, the prescription of serotonin-noradrenalin reuptake inhibitors (SNRIs) for treatment of fibromyalgia (FM) has increased with reports of their efficacy. The SNRI milnacipran is approved by the U.S. Food and Drug Administration (FDA) for treatment of FM, yet, the mechanisms by which milnacipran reduces FM symptoms are unknown. A large number of neuroimaging studies have demonstrated altered brain function in patients with FM but the effect of milnacipran on central pain processing has not been investigated. The primary objective of this study was to assess the effect of milnacipran on sensitivity to pressure-evoked pain in FM. Secondary objectives were to assess the effect of milnacipran on cerebral processing of pressure-evoked pain using fMRI and the tolerability and safety of milnacipran 200mg/day in FM. Methods92 patients were randomized to either 13-weeks milnacipran treatment (200mg/day) or placebo in this double-blind, placebo-controlled multicenter clinical trial. Psychophysical measures and functional MRI (fMRI) assessments were performed before and after treatment using a computer-controlled pressure-pain stimulator. Here, we present the results of several a priori defined statistical analyses. ResultsMilnacipran-treated patients displayed a trend toward lower pressure-pain sensitivity after treatment, compared to placebo, and the difference was greater at higher pain intensities. A single group fMRI analysis of milnacipran-treated patients indicated increased pain-evoked brain activity in the caudatus nucleus, anterior insula and amygdala after treatment, compared to before treatment; regions implicated in pain inhibitory processes. A 2×2 repeated measures fMRI analysis, comparing milnacipran and placebo, before and after treatment, showed that milnacipran-treated patients had greater pain-evoked activity in the precuneus/posterior cingulate cortex after treatment; a region previously implicated in intrinsic brain function and FM pathology. This finding was only significant when uncorrected for multiple comparisons. The safety analysis revealed that patients from both treatment groups had treatment-emergent adverse events where nausea was the most common complaint, reported by 43.5% of placebo patients and 71.7% of milnacipran-treated patients. Patients on milnacipran were more likely to discontinue treatment because of side effects. ConclusionsOur results provide preliminary indications of increased pain inhibitory responses in milnacipran-treated FM patients, compared to placebo. The psychophysical assessments did not reach statistical significance but reveal a trend toward higher pressure-pain tolerance after treatment with milnacipran, compared to placebo, especially for higher pain intensities. Our fMRI analyses point toward increased activation of the precuneus/posterior cingulum in patients treated with milnacipran, however results were not corrected for multiple comparisons. The precuneus/posterior cingulum is a key region of the default mode network and has previously been associated with abnormal function in FM. Future studies may further explore activity within the default mode network as a potential biomarker for abnormal central pain processing. ImplicationsThe present study provides novel insights for future studies where functional neuroimaging may be used to elucidate the central mechanisms of common pharmacological treatments for chronic pain. Furthermore, our results point toward a potential mechanism for pain normalization in response to milnacipran, involving regions of the default mode network although this finding needs to be replicated in future studies.

Cognitive Performance in Women Aged 50 Years and Older With and Without Fibromyalgia

Persons with fibromyalgia (FM) report having cognitive dysfunction. Neuropsychological performance was compared across a variety of domains in 43 women with FM (Mage = 63 years) and in 44 women without FM (Mage = 65 years). Measures included explicit memory (Consortium to Establish a Registry for Alzheimer's Disease [CERAD] immediate/delayed recall, delayed recognition), aspects of executive function including interference/inhibition (Stroop Color/Word test), working memory (Digit Span Forward/Backward), set-shifting/complex sequencing (Trails B), monitoring (verbal fluency: naming animals), processing speed (Trails A, Digit Symbol Substitution Coding), and problem solving (Everyday Problems Test). Women with FM performed more poorly than controls on executive function (Stroop Color/Word) and one processing speed measure (Digit Symbol Substitution Coding). Results partly support altered cognitive function in FM. Mixed findings across cognitive domains among individuals with or without FM is consistent with the literature and suggest that factors beyond those typically controlled for (e.g., heterogeneity in FM) may be influencing findings. Future research is warranted.

Autonomic changes in fibromyalgia: Clinical and electrophysiological study

BackgroundAutonomic nervous system (ANS) dysfunction is one of the suggested pathophysiological mechanisms of fibromyalgia (FM). Its dysfunction may contribute to enhanced pain and other clinical problems associated with FM. Previous studies showed conflicting results regarding ANS function in FM. Some studies showed increased while others showed decreased ANS activity in FM patients. Thus, the autonomic responses in FM patients need further elaboration. Aim of the workThe aim of this work was to evaluate the autonomic dysfunction in FM patients clinically and electrophysiologically. Subjects and methodsTwenty-five patients (23 females and 2 males) diagnosed as FM and 15 apparently healthy individuals served as a control group were included in this study. Patients were subjected to thorough clinical examination and assessment of 1 – pain by McGill pain questionnaire (MPQ), 2 – sleep by Visual Analogue Scale (VAS), 3 – depression by Hamilton Rating Scale for Depression (HRSD) and 4 – functional status by Fibromyalgia impact questionnaire (FIQ). Assessment of ANS function was carried out by tilt table test, measuring supine and standing blood pressure (BP) and heart rate (HR) and sympathetic skin response (SSR) of the hands. ResultsCompared to controls, there was a statistically significant decrease of standing systolic BP standing, diastolic BP and standing HR as well as a statistically significant increase in latency and decrease in amplitude of SSR of the hands of the FM patients. HRSD was correlated positively with supine systolic BP and standing diastolic BP while McGill pain questionnaire was correlated positively with supine systolic BP. Moreover, VAS falling asleep was correlated positively with standing systolic BP. ConclusionThe studied FM patients showed ANS dysfunction in the form of abnormal responses to active and passive changes in posture as well as abnormal SSR.

An International, Randomized, Double-blind, Placebo-controlled, Phase III Trial of Pregabalin Monotherapy in Treatment of Patients with Fibromyalgia

To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States. This international, multicenter, double-blind, placebo-controlled trial randomly assigned 747 patients with FM to placebo or 300, 450, or 600 mg/day pregabalin twice daily for 14 weeks. Primary efficacy measures were endpoint mean pain scores and Patient Global Impression of Change (PGIC). Secondary outcomes included assessments of sleep and function. Patients in the 450 mg/day pregabalin group showed significant improvements versus placebo in endpoint mean pain score (-0.56; p = 0.0132), PGIC (73% improved vs 56% placebo; p = 0.0017), and function [Fibromyalgia Impact Questionnaire (FIQ) total score -5.85; p = 0.0012]. PGIC was also significant for 600 mg/day pregabalin (69% improved; p = 0.0227). Results for these endpoints were nonsignificant for pregabalin at 300 mg/day and for pain and FIQ score at 600 mg/day. Early onset of pain relief was seen, with separation from placebo detected by Week 1 in all pregabalin groups. All pregabalin doses demonstrated superiority to placebo on the Medical Outcomes Study-Sleep Scale Sleep Disturbance subscale and the Sleep Quality diary. Dizziness and somnolence were the most frequently reported adverse events. Pregabalin demonstrated modest efficacy in pain, global assessment, and function in FM at 450 mg/day, and improved sleep across all dose levels, but it did not provide consistent evidence of benefit at 300 and 600 mg/day in this study. Pregabalin was generally well tolerated for the treatment of FM. (Clinical trial registry NCT00333866).

Salivary Cortisol Release and Hypothalamic Pituitary Adrenal Axis Feedback Sensitivity in Fibromyalgia Is Associated With Depression But Not With Pain

Results on hypothalamicpituitary-adrenal (HPA) axis function in fibromyalgia are heterogeneous and studies that integrate psychological and biological mechanisms in the search for pathways to fibromyalgia are rare. The goal of the study was to evaluate cortisol release and HPA axis feedback regulation in fibromyalgia and its association with psychopathology and pain. Beneath assessment of pain thresholds and self-report of pain, salivary free cortisol release over the day before and after intake of 0.5 mg of dexamethasone was measured in 21 female patients with fibromyalgia and 26 control women. Depression was assessed by questionnaires and clinical interview. We found reduced feedback sensitivity and slightly enhanced cortisol release in patients with fibromyalgia compared with healthy control subjects. Post hoc analyses showed that these effects are exclusively found in those patients, who also had major depressive disorder. Patients with fibromyalgia had lower pain pressure threshold, whereas heat pain thresholds were comparable with control subjects. Pain pressure and heat pain thresholds were not associated with cortisol release. On the other hand measurements of affective pain experience and depression were positively correlated with salivary cortisol over the day. Our results support the hypotheses that HPA axis related alterations are associated with affective disturbances, for example, depression, in patients with fibromyalgia. The presented data suggest depression to be an important factor in HPA axis-related dysfunction in fibromyalgia. This might be one explanation for equivocal findings in the literature.

Alteration of cortical excitability in patients with fibromyalgia

We assessed cortical excitability and intracortical modulation systematically, by transcranial magnetic stimulation (TMS) of the motor cortex, in patients with fibromyalgia. In total 46 female patients with fibromyalgia and 21 normal female subjects, matched for age, were included in this study. TMS was applied to the hand motor area of both hemispheres and motor evoked potentials (MEPs) were recorded for the first interosseous muscle of the contralateral hand. Single-pulse stimulation was used for measurements of the rest motor threshold (RMT) and suprathreshold MEP. Paired-pulse stimulation was used to assess short intracortical inhibition (SICI) and intracortical facilitation (ICF). Putative correlations were sought between changes in electrophysiological parameters and major clinical features of fibromyalgia, such as pain, fatigue, anxiety, depression and catastrophizing. The RMT on both sides was significantly increased in patients with fibromyalgia and suprathreshold MEP was significantly decreased bilaterally. However, these alterations, suggesting a global decrease in corticospinal excitability, were not correlated with clinical features. Patients with fibromyalgia also had lower ICF and SICI on both sides, than controls, these lower values being correlated with fatigue, catastrophizing and depression. These neurophysiological alterations were not linked to medication, as similar changes were observed in patients with or without psychotropic treatment. In conclusion, fibromyalgia is associated with deficits in intracortical modulation involving both GABAergic and glutamatergic mechanisms, possibly related to certain aspects of the pathophysiology of this chronic pain syndrome. Our data add to the growing body of evidence for objective and quantifiable changes in brain function in fibromyalgia.

Lack of DREAM Protein Enhances Learning and Memory and Slows Brain Aging

Memory deficits in aging affect millions of people and are often disturbing to those concerned. Dissection of the molecular control of learning and memory is paramount to understand and possibly enhance cognitive functions. Old-age memory loss also has been recently linked to altered Ca(2+) homeostasis. We have previously identified DREAM (downstream regulatory element antagonistic modulator), a member of the neuronal Ca(2+) sensor superfamily of EF-hand proteins, with specific roles in different cell compartments. In the nucleus, DREAM is a Ca(2+)-dependent transcriptional repressor, binding to specific DNA signatures, or interacting with nucleoproteins regulating their transcriptional properties. Also, we and others have shown that dream mutant (dream(-/-)) mice exhibit marked analgesia. Here we report that dream(-/-) mice exhibit markedly enhanced learning and synaptic plasticity related to improved cognition. Mechanistically, DREAM functions as a negative regulator of the key memory factor CREB in a Ca(2+)-dependent manner, and loss of DREAM facilitates CREB-dependent transcription during learning. Intriguingly, 18-month-old dream(-/-) mice display learning and memory capacities similar to young mice. Moreover, loss of DREAM protects from brain degeneration in aging. These data identify the Ca(2+)-regulated "pain gene" DREAM as a novel key regulator of memory and brain aging.

Predicting High Physical Function in People With Fibromyalgia

The purpose of this study was to investigate predictors of high physical function in people with fibromyalgia (FM). Cross-sectional descriptive, correlational study of 2,580 persons with FM who responded to an online survey during fall 2005. The survey indicated self-reported physical activity levels, functional abilities, symptoms, health care costs, employment status, work productivity, self management strategies. It had adequate validity and reliability. A significant binary logistic regression model of predictors of physical function (individual factors, symptoms, self management strategies) was validated using backwards logistic regression. Significant explanatory variables of high physical function were: men, greater education, younger age, lower intensity fatigue, spasticity, and balance problems, not using prescription pain medications, using aerobic or strength training exercise, and not using relaxation methods. People with FM suffer from multiple symptoms and use many modalities to control symptoms to remain functional. Given knowledge of predictors of physical function in FM, health care providers might be able to develop strategies to promote better functioning. Prospective trials are needed to track the natural course of study variables, measuring their effect on function, and to test effects of interventions to maximize function.

Disautonomia: um conceito emergente na síndrome da fibromialgia

A síndrome da fibromialgia (SFM) é uma condição de dor crônica, generalizada e de difícil tratamento, com importante prevalência na população geral. A fibromialgia é mais do que um estado de dor musculoesquelética crônica, porque a maioria desses pacientes também experimenta fadiga, distúrbios de sono, dor visceral, intolerância a exercícios e sintomas neurológicos. É uma síndrome caracterizada mais por sintomas, sofrimento e incapacidades do que por alterações orgânicas estruturais demonstráveis, podendo fazer parte do grupo de síndromes funcionais. Muitas tentativas para elucidar a patogenia orgânica da SFM, como pesquisas em genética, aminas biogênicas, neurotransmissores, hormônios do eixo hipotálamo-hipófise-adrenal, estresse oxidativo, mecanismos de modulação da dor, sensibilização central e função autonômica na SFM, revelam várias anormalidades, indicando que múltiplos fatores e mecanismos podem estar envolvidos na patogênese dessa síndrome. A disautonomia pode ter um importante papel na fisiopatologia da SFM, embora não esteja claro se é causa ou efeito ou um componente deste mosaico. Pesquisas futuras devem ser encorajadas no sentido de se avaliar o papel do sistema nervoso autônomo ou sua disfunção na complexa fisiopatologia da SFM e a eficácia de intervenções terapêuticas por meio de ensaios controlados e randomizados. O desenvolvimento de terapias efetivas para a fibromialgia tem sido retardado pela falta de entendimento dos mecanismos fundamentais da etiologia da síndrome. Uma boa compreensão dos mecanismos é a base para o desenvolvimento e a comprovação de condutas terapêuticas adequadas. Esta revisão descreve os mais recentes artigos da literatura que demonstram haver uma desregulação no sistema nervoso autônomo na SFM e discute a disautonomia como um potencial mecanismo participante na gênese e manutenção da sintomatologia e comorbidades da SFM.

Cerebrospinal Fluid Corticotropin-Releasing Factor Concentration is Associated with Pain but not Fatigue Symptoms in Patients with Fibromyalgia

Previous studies have identified stress system dysregulation in fibromyalgia (FM) patients; such dysregulation may be involved in the generation and/or maintenance of pain and other symptoms. Corticotropin-releasing factor (CRF) is the principal known central nervous system mediator of the stress response; however, to date no studies have examined cerebrospinal fluid (CSF) CRF levels in patients with FM. The relationship between CSF CRF level, heart rate variability (HRV), and pain, fatigue, and depressive symptoms was examined in patients with FM. Among participants (n=26), CSF CRF levels were associated with sensory pain symptoms (r=0.574, p=0.003) and affective pain symptoms (r=0.497, p=0.011), but not fatigue symptoms. Increased HRV was also strongly associated with increased CSF CRF and FM pain. In multivariate analyses adjusting for age, sex, and depressive symptoms, the association between CSF CRF and sensory pain symptoms (t=2.54, p=0.027) persisted. Women with FM who reported a history of physical or sexual abuse had lower CSF CRF levels than women who did not report such a history. CSF CRF levels are associated with both pain symptoms and variation in autonomic function in FM. Differences in CSF CRF levels among women with and without a self-reported history of physical or sexual abuse suggest that subgroups of FM patients may exist with different neurobiological characteristics. Further studies are needed to better understand the nature of the association between CSF CRF and pain symptoms in FM.

Memory beliefs and function in fibromyalgia patients

Objective The aim of this study was to investigate memory beliefs and their relationship to actual memory function in fibromyalgia (FM) patients. Methods Twenty-three FM patients, 23 age- and education-matched controls, and 22 older controls completed the Metamemory in Adulthood (MIA) questionnaire, which assessed beliefs about seven aspects of memory function. Group differences on the seven scales were assessed, and scores on the capacity scale were correlated with objective memory performance. Results FM patients reported lower memory capacity and more memory deterioration than did either control group. Patients reported lower control or self-efficacy over memory, higher achievement motivation, higher strategy use, and higher anxiety about memory than age-matched controls did. Among the patients, perceived capacity, achievement motivation, and self-efficacy were significantly correlated with objective memory performance on a recall task. Conclusion FM patients' complaints about memory function have some accuracy.

Pain, psychological variables, sleep quality, and natural killer cell activity in midlife women with and without fibromyalgia*1

In women with fibromyalgia (FM), central nervous system (CNS) dysfunction in pain, mood, and sleep processes could be associated with changes in immune system indicators. The primary purpose of this study was to compare pain, psychological variables, subjective and objective sleep quality, lymphocyte phenotypes and activation markers, and natural killer activity (NKA) in midlife women with and without FM. A secondary purpose was to explore relationships among these variables in a step-wise regression. Subjects had pain pressure tender points assessed, completed a psychiatric interview and questionnaires (Beck Depression Inventory, SCL-90, Profile of Mood States, subjective sleep), and underwent polysomnograhic assessment for two consecutive nights. Lymphocyte phenotypes, activation markers, and NKA were assessed from blood drawn the morning after sleep laboratory night 2. Compared to controls, women with FM had lower pain thresholds, more psychological distress, higher depression scores, and reduced subjective and objective sleep quality. They also had fewer NK cells (p<.009) and more NK cells that expressed the IL-2 receptor (p<.04), but these differences were not statistically significant after correction for multiple comparisons. NKA was not statistically significantly lower in the women with FM compared to controls. In a multiple regression of age, tender point threshold, depression, psychological distress, and sleep efficiency, only the effect of group was significant (F=5.479, p<.03) on NKA. In conclusion, we found little evidence to support the hypothesis that pain, mood, and sleep symptoms are associated with changes in the enumeration of peripheral lymphocytes or function in FM.

Objective Levels of Physical Activity and Performance and Selfreported Physical Function in Fibromyalgia (FM) Patients

2097 Purpose: Interpretation of self-report physical function is confounded by a dearth of accurate and specific measures of physical activity and function. Patients' self-reports of physical function are likely obfuscated by illness beliefs and fear of ramifications. This study sought to determine if 2 surrogate measures of physical function (activity monitoring and submaximal exercise testing) were related to self-reported physical function in FM. Methods: Thirty-five FM patients (40.7 ± 9.6yr; 74% female) and 43 controls (CTL, 37.7 ± 9.1; 47% female) completed a submaximal bicycle test. The test consisted of continuous 3-min stages, culminating when HR reached 85% of agepredicted maximum. Peak exercise performance was de. ned as the highest wattage achieved. Of these subjects, 30 FM (41.5 ± 8.9; 77% female) and 29 CTL (38 ± 8.9, 48% female) also wore an activity monitor for 5 consecutive days and 4 nights. Activity was sampled in 30-sec epochs, averaged into 5-min intervals. Self-reported physical functioning was assessed via the SF-36 and the Multidimensional Fatigue Inventory. Results: Mean peak performance on the exercise test was lower for the FM group than CTL (98 ± 30 watts vs. 128 ± 43, p = 0.001). Average daytime and nighttime activity levels were similar between FM and CTL (daytime: 1456 ± 492 vs. 1445 ± 556 and nighttime: 147 ± 156 vs. 152 ± 107 activity units, respectively). However, peak activity was significantly lower in FM relative to CTL (7870 ± 3223 vs. 12178 ± 7862 activity units, p = 0.023), and was more variable. As expected, peak and average symptom ratings were higher in FM than CTL and SF-36 physical functioning scores were lower (SF-36 physical composite score: 35.6 ± 10.8 vs. 55.8 ± 5.4, p = 0.00). However, none of these variables were related to average or peak activity levels. No objective measure of activity (peak exercise performance or peak or average activity) was correlated with any self-report measure of function, or symptoms, in either the patient or control group (r's = −.05 to 0.23). Conclusions: FM patients report the lowest physical function among almost all rheumatic illnesses. Despite this, FM patients in this study were able to maintain a “normal” average level of activity relative to the controls, albeit with considerably greater variability. Peak physical function as evaluated by 2 different measures was not related to self-reported physical function in either FM or CTL. These observations suggest that factors other than pure physical movement influence selfreported functioning, and support the notion that peak activity levels and peak exercise performance are indices of “capacity” rather than indices of day-to-day patient ability.

Objective Levels of Physical Activity and Performance and Selfreported Physical Function in Fibromyalgia (FM) Patients

Objective Levels of Physical Activity and Performance and Selfreported Physical Function in Fibromyalgia (FM) Patients

Myofascial pain and fibromyalgia: Relationship of self-reported pain, tender point count, and evoked pressure pain sensitivity to cognitive function in Fibromyalgia

Although Fibromyalgia (FM) is defined on the basis of pain and tenderness, patients also complain of diminished cognitive function, and in one study, this was related to self-reported pain (Park et al., 2001). In this study, we examined the relationship between pain and cognitive function in FM using three measures of clinical and evoked pain. Data were from 39 controls (20 M, 19 F, mean 38yrs) and 33 FMs (7 M, 26 F, mean 41yrs). Cognition was measured by verbal working memory (Backward Digit Span) and visual-spatial recall (Benton Visual Retention Test). Clinical pain was measured by self-report (McGill Short Form) and tender point exam (tender point count). Evoked pressure pain sensitivity was measured with a multiple random staircase method that determined the stimulus pressure (kg) needed to produce mild pain for each subject. There were no differences on the cognitive measures between FMs and controls. Among FMs, self-reported pain, tender point count and pressure pain sensitivity were significantly correlated with verbal working memory and visual-spatial recall (.554 < r > .324). Among the controls, the associations were weaker and non-significant (.266 < r > .043). Separate regression analyses were performed for each cognitive measure using the three pain measures as predictors. For FMs each model was significant (verbal working memory, F(3, 23)=3.965, p=.02, R2= .341; visual-spatial recall, F(3, 22)=3.413, p=.035, R2=.318). Furthermore, pressure pain sensitivity was the best predictor of verbal working memory performance, whereas self-reported pain was the best predictor of visual-spatial recall. Among controls, neither model was significant (verbal working memory, R2= .082; visual-spatial recall, R2=.105). The results suggest that pain and cognitive function are related in FMs, but this association is not observed in controls. Future research will explore these mechanisms in FM and other chronic pain patient groups.

Pain, psychological variables, sleep quality, and natural killer cell activity in midlife women with and without fibromyalgia

In women with fibromyalgia (FM), central nervous system (CNS) dysfunction in pain, mood, and sleep processes could be associated with changes in immune system indicators. The primary purpose of this study was to compare pain, psychological variables, subjective and objective sleep quality, lymphocyte phenotypes and activation markers, and natural killer activity (NKA) in midlife women with and without FM. A secondary purpose was to explore relationships among these variables in a step-wise regression. Subjects had pain pressure tender points assessed, completed a psychiatric interview and questionnaires (Beck Depression Inventory, SCL-90, Profile of Mood States, subjective sleep), and underwent polysomnograhic assessment for two consecutive nights. Lymphocyte phenotypes, activation markers, and NKA were assessed from blood drawn the morning after sleep laboratory night 2. Compared to controls, women with FM had lower pain thresholds, more psychological distress, higher depression scores, and reduced subjective and objective sleep quality. They also had fewer NK cells ( p<.009) and more NK cells that expressed the IL-2 receptor ( p<.04), but these differences were not statistically significant after correction for multiple comparisons. NKA was not statistically significantly lower in the women with FM compared to controls. In a multiple regression of age, tender point threshold, depression, psychological distress, and sleep efficiency, only the effect of group was significant ( F=5.479, p<.03) on NKA. In conclusion, we found little evidence to support the hypothesis that pain, mood, and sleep symptoms are associated with changes in the enumeration of peripheral lymphocytes or function in FM.

Hypothalamic-Pituitary-Adrenal Axis Function in Fibromyalgia and Chronic Fatigue Syndrome

Patients with chronic fatigue syndrome (CFS) or fibromyalgia, two prevalent and poorly understood disorders, experience symptoms of fatigue and myalgias that are reminiscent of those experienced by patients with adrenal insufficiency. This overlap in symptoms has prompted investigations into the fun

Neuroendocrine abnormalities in fibromyalgia.

Fibromyalgia is a disorder of unknown etiology characterized by chronic, widespread musculoskeletal pain and symptoms such as fatigue, poor sleep, gastrointestinal complaints, and psychologic problems that are similar to those experienced by patients with hormone deficiencies. This review summarizes the available data on the neuroendocrine function in fibromyalgia, including data on hormone secretion, circadian phase, and autonomic nervous system function. Studies suggest that there may be lower activity of a number of hypothalamic-pituitary-peripheral gland axes and altered autonomic nervous system function in patients with fibromyalgia. These reductions in activity are mild to moderate and do not result from alterations in circadian rhythms. The reduced hormonal and autonomic responses appear to reflect an impairment in the hypothalamic or central nervous system response to stimuli rather than a primary defect at the level of the pituitary gland or the peripheral glands. A combination of multiple, mild impaired responses may lead to more profound physiologic and clinical consequences as compared with a defect in only one system, and could contribute to the symptoms of fibromyalgia.

Sympathetic nervous system function in fibromyalgia.

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.