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Showing papers on "Fibromyalgia published in 2005"


Journal ArticleDOI
TL;DR: Pregabalin at 450 mg/day was efficacious for the treatment of FMS, reducing symptoms of pain, disturbed sleep, and fatigue compared with placebo and was well tolerated and improved global measures and health-related quality of life.
Abstract: Objective Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain and lowered pain threshold. Other prominent symptoms include disordered sleep and fatigue. FMS affects an estimated 2% of the population, predominantly women. This trial was designed to evaluate the efficacy and safety of pregabalin, a novel α2-δ ligand, for treatment of symptoms associated with FMS. Methods This multicenter, double-blind, 8-week, randomized clinical trial compared the effects of placebo with those of 150, 300, and 450 mg/day pregabalin on pain, sleep, fatigue, and health-related quality of life in 529 patients with FMS. The primary outcome variable was the comparison of end point mean pain scores, derived from daily diary ratings of pain intensity, between each of the pregabalin treatment groups and the placebo group. Results Pregabalin at 450 mg/day significantly reduced the average severity of pain in the primary analysis compared with placebo (−0.93 on a 0–10 scale) (P ≤ 0.001), and significantly more patients in this group had ≥50% improvement in pain at the end point (29%, versus 13% in the placebo group; P = 0.003). Pregabalin at 300 and 450 mg/day was associated with significant improvements in sleep quality, fatigue, and global measures of change. Pregabalin at 450 mg/day improved several domains of health-related quality of life. Dizziness and somnolence were the most frequent adverse events. Rates of discontinuation due to adverse events were similar across all 4 treatment groups. Conclusion Pregabalin at 450 mg/day was efficacious for the treatment of FMS, reducing symptoms of pain, disturbed sleep, and fatigue compared with placebo. Pregabalin was well tolerated and improved global measures and health-related quality of life.

627 citations


Journal ArticleDOI
01 Mar 2005-Pain
TL;DR: A deficit of endogenous pain inhibitory systems in fibromyalgia but not in chronic low back pain is supported, and the treatments proposed to fibromyalgic patients should aim at stimulating the activity of those endogenous systems.
Abstract: A deficit of endogenous pain inhibitory systems has been suggested to contribute to some chronic pain conditions, one of them being fibromyalgia. The aim of the investigation was to test whether endogenous pain inhibitory systems were activated by a spatial summation procedure in 30 fibromyalgia, 30 chronic low back pain, and 30 healthy volunteers who participated in a cross-over trial (two sessions). Each session consisted of visual analog scale ratings of pain during the immersion of different surfaces of the arm in circulating noxious cold (12 degrees C) water. The arm was arbitrarily divided into eight segments from the fingertips to the shoulder. One session was ascending (from the fingertips to the shoulder) and the other was descending (from the shoulder to the fingertips); they included eight consecutive 2-min immersions separated by 5-min resting periods. For healthy and low back pain subjects, pain was perceived differently during the ascending and descending sessions (P=0.0001). The descending session resulted in lower pain intensity and unpleasantness. This lowering of the perception curve seems to be due to a full recruitment of inhibitory systems at the beginning of the descending session as opposed to a gradual recruitment during the ascending session. For fibromyalgia subjects, no significant differences were found between the increasing and decreasing sessions (P>0.05). These data support a deficit of endogenous pain inhibitory systems in fibromyalgia but not in chronic low back pain. The treatments proposed to fibromyalgia patients should aim at stimulating the activity of those endogenous systems.

572 citations


Journal Article
TL;DR: The multifaceted nature of FM suggests that multimodal individualized treatment programs may be necessary to achieve optimal outcomes in patients with this syndrome.
Abstract: 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.

543 citations


Journal ArticleDOI
TL;DR: Higher levels of overall positive affect predicted lower levels of pain in subsequent weeks, and both higher weekly positive affect as well as greater positive affect on average resulted in lower negative affect both directly and in interaction with pain and stress.
Abstract: A sample of 124 women with osteoarthritis or fibromyalgia, or both, completed initial assessments for demographic data, health status, and personality traits and 10-12 weekly interviews regarding pain, stress, negative affect, and positive affect. Multilevel modeling analyses indicated that weekly elevations of pain and stress predicted increases in negative affect. Both higher weekly positive affect as well as greater positive affect on average resulted in lower negative affect both directly and in interaction with pain and stress. Finally, increases in weekly negative affect and higher average negative affect related to greater levels of pain in subsequent weeks. In contrast, higher levels of overall positive affect predicted lower levels of pain in subsequent weeks.

507 citations


Journal ArticleDOI
15 Dec 2005-Pain
TL;DR: Both doses of duloxetine were effective and safe in the treatment of fibromyalgia in female patients with or without major depressive disorder and several quality‐of-life measures.
Abstract: This was a 12-week, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, in 354 female patients with primary fibromyalgia, with or without current major depressive disorder. Patients (90% Caucasian; mean age, 49.6 years; 26% with current major depressive disorder) received duloxetine 60 mg once daily (QD) (N=118), duloxetine 60 mg twice daily (BID) (N=116), or placebo (N=120). The primary outcome was the Brief Pain Inventory average pain severity score. Response to treatment was defined as >or=30% reduction in this score. Compared with placebo, both duloxetine-treated groups improved significantly more (P or=30% in this score (duloxetine 60 mg QD (55%; P<0.001); duloxetine 60 mg BID (54%; P=0.002); placebo (33%)). The treatment effect of duloxetine on pain reduction was independent of the effect on mood and the presence of major depressive disorder. Compared with patients on placebo, patients treated with duloxetine 60 mg QD or duloxetine 60 mg BID had significantly greater improvement in remaining Brief Pain Inventory pain severity and interference scores, Fibromyalgia Impact Questionnaire, Clinical Global Impression of Severity, Patient Global Impression of Improvement, and several quality-of-life measures. Both doses of duloxetine were safely administered and well tolerated. In conclusion, both duloxetine 60 mg QD and duloxetine 60 mg BID were effective and safe in the treatment of fibromyalgia in female patients with or without major depressive disorder.

449 citations


Journal ArticleDOI
TL;DR: There are parallel, somewhat independent neural pain-processing networks for sensory and affective pain elements in patients with fibromyalgia, suggesting that addressing an individual's depression will not necessarily have an impact on the sensory dimension of pain.
Abstract: Objective. Individuals with chronic pain frequently display comorbid depression, but the impact of symptoms of depression on pain processing is not completely understood. This study evaluated the effect of symptoms of depression and/or clinically diagnosed major depressive disorder (MDD) on pain processing in patients with fibromyalgia (FM). Methods. Results of quantitative sensory testing and neural responses to equally painful pressure stimuli (measured by functional magnetic resonance imaging [fMRI]) were compared with the levels of symptoms of depression and comorbid MDD among patients with FM. Results. Neither the level of symptoms of depression nor the presence of comorbid MDD was associated with the results of sensory testing or the magnitude of neuronal activation in brain areas associated with the sensory dimension of pain (primary and secondary somatosensory cortices). However, symptoms of depression and the presence of MDD were associated with the magnitude of pain-evoked neuronal activations in brain regions associated with affective pain processing (the amygdalae and contralateral anterior insula). Clinical pain intensity was associated with measures of both the sensory dimension of pain (results of sensory testing) and the affective dimension of pain (activations in the insula bilaterally, contralateral anterior cingulate cortex, and prefrontal cortex). Conclusion. In patients with FM, neither the extent of depression nor the presence of comorbid major depression modulates the sensory-discriminative aspects of pain processing (i.e., localizing pain and reporting its level of intensity), as measured by sensory testing or fMRI. However, depression is associated with the magnitude of neuronal activation in brain regions that process the affective-motivational dimension of pain. These data suggest that there are parallel, somewhat independent neural pain-processing networks for sensory and affective pain elements. The implication for treatment is that addressing an individual’s depression (e.g., by prescribing an antidepressant medication that has no analgesic properties) will not necessarily have an impact on the sensory dimension of pain.

364 citations


Journal ArticleDOI
01 Jul 2005-Pain
TL;DR: Van Damme et al. as discussed by the authors offered conceptual clarification of the concept of hypervigilance, and proposed a model of hyper-vigilantance to explain gender differences in pain experience.
Abstract: A clinical feature of many chronic pain patients is persistent, distressing and preoccupying pain that cannot be explained easily by observable biomedical phenomena. Growing in popularity are explanations based on the idea of dysfunctional attentional processes. Patients are thought to display a ‘hypervigilance’ to pain and pain-associated information at the expense of the rest of life. Although seductive as an explanation for a class of effects, closer examination shows that there is a number of partial and competing explanations of this putative attentional effect, and different ways to operationalise it (Van Damme et al., 2004a,b). For just three examples: Puzzled by the observation that patients with widespread musculoskeletal pain have both lower pain and auditory thresholds than controls, McDermid et al. (1996) proposed that fibromyalgia patients are hypervigilant to stressors in general. In reviewing gender differences in pain experience, Rollman et al. (2004) suggested that hypervigilance may explain commonly found gender differences in the reporting of pain. In their model of fear-avoidance Vlaeyen and Linton (2000) presumed low back pain patients who fear (re)injury to be hypervigilant to pain; a hypervigilance that expedites escape and avoidance behavior. In this paper we offer conceptual clarification of the concept of vigilance, and propose a model of hypervigilance.

343 citations


Journal ArticleDOI
01 Nov 2005-Pain
TL;DR: The findings suggest that patients with CTTH suffer from deficient DNIC‐like pain inhibitory mechanisms in a similar manner, as do patients with anatomically generalized chronic pain like fibromyalgia.
Abstract: Evidence has been accumulated suggesting that a dysfunction in pain inhibitory systems, i.e. in ‘diffuse noxious inhibitory controls‘ (DNIC)-like mechanisms, might be—amongst other factors—responsible for the development of anatomically generalized chronic pain like fibromyalgia. The aim of the present study was to look for similar impairments in chronic tension-type headache (CTTH) as a regionally specific pain syndrome. Twenty-nine CTTH patients and 25 age- and sex-matched healthy control subjects participated in the study. After baseline assessment of electrical detection and pain thresholds, tonic heat stimuli were concurrently applied by a thermode to the thigh to induce DNIC-like pain inhibition. Tonic heat stimuli were applied either slightly above (‘pain’ condition) or slightly below (‘heat’ condition) pain threshold. For determination of electrical detection and pain thresholds, electrocutaneous stimuli were administered either to the forearm (extra-cranial site) or to the temple (cranial site), using a multiple staircase procedure. The increase in the electrical detection and pain thresholds induced by concurrent tonic heat stimulation was significantly smaller in the CTTH patients than in the control subjects. This group difference was present during the ‘pain’ as well as the ‘heat’ condition. Furthermore, the electrical detection and pain thresholds were affected in this group-specific manner both at the forearm and at the temple. These findings suggest that patients with CTTH suffer from deficient DNIC-like pain inhibitory mechanisms in a similar manner, as do patients with anatomically generalized chronic pain like fibromyalgia.

292 citations


Journal ArticleDOI
TL;DR: Treatment with pramipexole improved scores on assessments of pain, fatigue, function, and global status, and was safe and well-tolerated in a subset of patients with fibromyalgia.
Abstract: Objective. To assess the efficacy and safety of pramipexole, a dopamine 3 receptor agonist, in patients with fibromyalgia. Methods. In this 14-week, single-center, doubleblind, placebo-controlled, parallel-group, escalatingdose trial, 60 patients with fibromyalgia were randomized 2:1 (pramipexole:placebo) to receive 4.5 mg of pramipexole or placebo orally every evening. The primary outcome was improvement in the pain score (10-cm visual analog scale [VAS]) at 14 weeks. Secondary outcome measures were the Fibromyalgia Impact Questionnaire (FIQ), the Multidimensional Health Assessment Questionnaire (MDHAQ), the pain improvement scale, the tender point score, the 17-question Hamilton Depression Inventory (HAM-d), and the Beck Anxiety Index (BAI). Patients with comorbidities and disability were not excluded. Stable dosages of concomitant medications, including analgesics, were allowed. Results. Compared with the placebo group, patients receiving pramipexole experienced gradual and more significant improvement in measures of pain, fatigue, function, and global status. At 14 weeks, the VAS pain score decreased 36% in the pramipexole arm and 9% in the placebo arm (treatment difference –1.77 cm). Forty-two percent of patients receiving pramipexole and 14% of those receiving placebo achieved >50% decrease in pain. Secondary outcomes favoring pramipexole over placebo included the total FIQ score (treatment difference –9.57) and the percentages of improvement in function (22% versus 0%), fatigue (29% versus 7%), and global (38% versus 3%) scores on the MDHAQ. Compared with baseline, some outcomes showed a better trend for pramipexole treatment than for placebo, but failed to reach statistical significance, including improvement in the tender point score (51% versus 36%) and decreases in the MDHAQ psychiatric score (37% versus 28%), the BAI score (39% versus 27%), and the HAM-d score (29% versus 9%). No end points showed a better trend for the placebo arm. The most common adverse events associated with pramipexole were transient anxiety and weight loss. No patient withdrew from the study because of inefficacy or an adverse event related to pramipexole. Conclusion. In a subset of patients with fibromyalgia, 50% of whom required narcotic analgesia and/or were disabled, treatment with pramipexole improved scores on assessments of pain, fatigue, function, and global status, and was safe and well-tolerated.

290 citations


Journal ArticleDOI
TL;DR: Cognitive-behavioral therapy represents a promising intervention for sleep disturbance in FM patients and larger clinical trials of this intervention with FM patients seem warranted.
Abstract: Background Insomnia is common and debilitating to fibromyalgia (FM) patients. Cognitive-behavioral therapy (CBT) is effective for many types of patients with insomnia, but has yet to be tested with FM patients. This study compared CBT with an alternate behavioral therapy and usual care for improving sleep and other FM symptoms. Methods This randomized clinical trial enrolled 47 FM patients with chronic insomnia complaints. The study compared CBT, sleep hygiene (SH) instructions, and usual FM care alone. Outcome measures were subjective (sleep logs) and objective (actigraphy) total sleep time, sleep efficiency, total wake time, sleep latency, wake time after sleep onset, and questionnaire measures of global insomnia symptoms, pain, mood, and quality of life. Results Forty-two patients completed baseline and continued into treatment. Sleep logs showed CBT-treated patients achieved nearly a 50% reduction in their nocturnal wake time by study completion, whereas SH therapy– and usual care–treated patients achieved only 20% and 3.5% reductions on this measure, respectively. In addition, 8 (57%) of 14 CBT recipients met strict subjective sleep improvement criteria by the end of treatment compared with 2 (17%) of 12 SH therapy recipients and 0% of the usual care group. Comparable findings were noted for similar actigraphic improvement criteria. The SH therapy patients showed favorable outcomes on measures of pain and mental well-being. This finding was most notable in an SH therapy subgroup that self-elected to implement selected CBT strategies. Conclusions Cognitive-behavioral therapy represents a promising intervention for sleep disturbance in FM patients. Larger clinical trials of this intervention with FM patients seem warranted.

288 citations


Journal ArticleDOI
TL;DR: Whiplash subjects showed additional widespread hypersensitivity to mechanical pressure and thermal stimuli, which was independent of state anxiety and may represent changes in central pain processing mechanisms.
Abstract: Objectives: To investigate sensory changes present in patients with chronic whiplash-associated disorders and chronic idiopathic neck pain using a variety of quantitative sensory tests to better understand the pain processing mechanisms underlying persistent symptoms. Methods: A case control study was used with 29 subjects with chronic whiplash-associated disorders, 20 subjects with chronic idiopathic neck pain, and 20 pain-free volunteers. Pressure pain thresholds were measured over the articular pillars of C2-C3, C5-C6, the median, radial, and ulnar nerve trunks in the arm and over a remote site, the muscle belly of tibialis anterior. Heat pain thresholds, cold pain thresholds, and von Frey hair sensibility were measured over the cervical spine, tibialis anterior, and deltoid insertion. Anxiety was measured with the Short-Form of the Spielberger State Anxiety Inventory. Results: Pressure pain thresholds were decreased over cervical spine sites in both subject groups when compared with controls (P 0.27). No abnormalities in von Frey hair sensibility were evident in either neck pain group (P > 0.28). Discussion: Both chronic whiplash-associated disorders and idiopathic neck pain groups were characterized by mechanical hyperalgesia over the cervical spine. Whiplash subjects showed additional widespread hypersensitivity to mechanical pressure and thermal stimuli, which was independent of state anxiety and may represent changes in central pain processing mechanisms. This may have implications for future treatment approaches.

Journal ArticleDOI
TL;DR: The author suggests that the lack of satisfactory treatment outcomes for the treatments of chronic pain syndromes may be accounted for by the patient homogeneity myth-the assumption that all patients with the same medical diagnosis are similar on all important variables.
Abstract: A large and diverse number of treatments have been shown to be effective in reducing pain and other symptoms for a minority but statistically significant number of patients in different chronic pain syndromes. The means by which such different treatments achieve similar outcomes is not well understood. In this paper, the importance of considering patient heterogeneity for those who may be diagnosed with the same medical syndrome is discussed. The author suggests that the lack of satisfactory treatment outcomes for the treatments of chronic pain syndromes may be accounted for by the patient homogeneity myth--the assumption that all patients with the same medical diagnosis are similar on all important variables. The importance of subdividing (splitting) patients into meaningful groups is described. Studies presenting data on the identification of patient subgroups based on psychosocial and behavioral characteristics and the reliability and validity of this approach are presented. Some initial attempts to demonstrate the potential for matching treatments to patient subgroups are described.

Journal ArticleDOI
TL;DR: A model is proposed in which central neurobiological systems, including physiologic systems and neuroanatomical structures involved in the stress response, are an important substrate for the development of all 3 disorders and interact with psychosocial and other factors to influence chronic symptom development.
Abstract: OBJECTIVES: Persistent pain and psychological sequelae are common after motor vehicle collision (MVC), but their etiology remains poorly understood. Such common sequelae include whiplash-associated disorders (WAD), fibromyalgia, and posttraumatic stress disorder (PTSD). Increasing evidence suggests that these disorders share overlapping epidemiologic and clinical features. A model is proposed in which central neurobiological systems, including physiologic systems and neuroanatomical structures involved in the stress response, are an important substrate for the development of all 3 disorders and interact with psychosocial and other factors to influence chronic symptom development. METHODS: Epidemiologic and clinical characteristics regarding the development of these disorders after MVC are reviewed. Evidence suggesting a role for stress response systems in the development of these disorders is presented. RESULTS: Contemporary evidence supports a model of chronic symptom development that incorporates the potential for interactions between past experience, acute stress responses to trauma, post-MVC behavior, and cognitive/psychosocial consequences to alter activity within brain regions which process pain and to result in persistent pain, as well as psychological sequelae, after MVC. Such a model incorporates factors identified in prior biopsychosocial theories and places them in the landscape of our rapidly developing understanding of stress systems and CNS pain-modulating pathways. CONCLUSION: New models are needed to stimulate deeper examination of the interacting influences of initial tissue damage, acute pain, psychosocial contingencies, and central stress pathways during chronic symptom development after MVC. Deeper understanding could contribute to improved treatment approaches to reduce the immense personal and societal burdens of common trauma-related disorders. Language: en

Journal ArticleDOI
01 Nov 2005-Pain
TL;DR: The widespread hyperalgesic effects of exercise on FM patients clearly indicate altered central pain mechanisms, however, whether these exercise effects of FM patients result from abnormal descending inhibition or excessive activation of muscle nociceptive afferents needs to be addressed in future studies.
Abstract: Aerobic exercise has been shown to activate endogenous opioid and adrenergic systems and attenuate experimental pain in normal control subjects (NC). In contrast, fibromyalgia (FM) subjects' experimental pain ratings increase after aerobic exercise, suggestive of abnormal pain modulation. In order to determine whether central or peripheral mechanisms are predominantly involved in the abnormal pain modulation of FM patients, the effects of handgrip exercise on thermal (cutaneous) and mechanical (somatic) experimental pain was tested in local as well as remote body areas of FM and NC subjects. Supra-threshold thermal pain ratings and pressure pain thresholds over both forearms were obtained before and during 90 s of sustained 30% maximal voluntary contraction (MVC). This isometric exercise resulted in substantially decreased thermal pain ratings and increased mechanical thresholds in local as well as remote body areas in NC. Opposite effects were detected in FM patients. Thus, sustained local muscular contraction induced widespread pain inhibitory effects in NC. In contrast, the widespread hyperalgesic effects of exercise on FM patients clearly indicate altered central pain mechanisms. However, whether these exercise effects of FM patients result from abnormal descending inhibition or excessive activation of muscle nociceptive afferents needs to be addressed in future studies.

Journal ArticleDOI
TL;DR: This review summarizes evidence, primarily from recent human studies, indirectly supporting a novel hypothesis: that the assessment of healthy individuals’ responses to standardized noxious stimuli in a controlled laboratory environment has important implications for the later risk of developing a broad spectrum of chronically painful conditions.
Abstract: This review summarizes evidence, primarily from recent human studies, indirectly supporting a novel hypothesis: that the assessment of healthy individuals' responses to standardized noxious stimuli in a controlled laboratory environment has important implications for the later risk of developing a broad spectrum of chronically painful conditions. Descriptions of many chronic pain syndromes note that the disorder (e.g., fibromyalgia, headache, complex regional pain syndrome) is associated with hypersensitivity to pain and with reduced endogenous inhibition of pain, implying that an individual's processing of pain-related information changes with the onset of the syndrome. However, pain sensitivity and pain-inhibitory capacity are normally distributed along a wide continuum in the general population, and recent evidence suggests that heightened baseline pain sensitivity and reduced basal pain-inhibitory processing place individuals at greater risk for experiencing severe, acute, clinical pain (e.g., postoperative pain). More controversial is the hypothesis that such individual-difference characteristics confer risk for, or protection against, chronic pain; although only a single prospective study has been published, substantial indirect evidence supports the contention that greater basal pain sensitivity and reduced pain-inhibitory capacity may act as a diathesis for chronic pain. Long-term cohort studies are necessary to test this hypothesis; such research could yield insight into the nature of chronic pain and permit greater precision in selecting high-risk individuals for chronic pain prevention research.

Journal Article
TL;DR: In this Phase II study, milnacipran led to statistically significant improvements in pain and other symptoms of FM, the effect sizes were equal to those previously found with TCA, and the drug was generally well tolerated.
Abstract: OBJECTIVE: Fibromyalgia (FM) is a common musculoskeletal condition characterized by widespread pain, tenderness, and a variety of other somatic symptoms. Current treatments are modestly effective. Arguably, the best studied and most effective compounds are tricyclic antidepressants (TCA). Milnacipran, a nontricyclic compound that inhibits the reuptake of both serotonin and norepinephrine, may provide many of the beneficial effects of TCA with a superior side effect profile. METHODS: One hundred twenty-five patients with FM were randomly assigned in a 3:3:2 ratio to receive milnacipran twice daily, milnacipran once daily, or placebo for 3 months in a double-blind dose-escalation trial; 92% of twice-daily and 81% of once-daily participants achieved dose escalation to the target milnacipran dose of 200 mg. RESULTS: The primary endpoint was reduction of pain. Both the once- and twice-daily groups showed statistically significant improvements in pain, as well as improvements in global well being, fatigue, and other domains. Response rates for patients receiving milnacipran were equal in patients with and without comorbid depression, but placebo response rates were considerably higher in depressed patients, leading to significantly greater overall efficacy in the nondepressed group. CONCLUSION: In this Phase II study, milnacipran led to statistically significant improvements in pain and other symptoms of FM. The effect sizes were equal to those previously found with TCA, and the drug was generally well tolerated.

Journal ArticleDOI
TL;DR: Nonrestorative sleep affected more frequently the active classes of the population and caused greater daytime impairment than difficulty initiating or maintaining sleep.
Abstract: Background Nonrestorative sleep (NRS) has been little studied in the general population, even though this symptom has an important role in several medical conditions such as heart disease, fibromyalgia, and chronic fatigue syndrome, as well as various sleep disorders. Methods A total of 25 580 individuals (age range, 15-100 years) from the noninstitutionalized general population representative of 7 European countries (France, the United Kingdom, Germany, Italy, Portugal, Spain, and Finland) were interviewed by telephone using the Sleep-EVAL system. Nonrestorative sleep was analyzed in relationship to sociodemographic determinants, environmental factors, life habits, health, sleep-wake schedule, and psychological factors. Results The prevalence of NRS was 10.8% (95% confidence interval, 10.4%-11.2%) in the sample, was higher in women than in men (12.5% vs 9.0%; P Conclusions Nonrestorative sleep is a frequent symptom in the general population, but its prevalence largely varies between countries. It is often associated with mental disorders and characteristics of sleep deprivation (such as extra sleep time on weekends). Nonrestorative sleep affected more frequently the active classes of the population and caused greater daytime impairment than difficulty initiating or maintaining sleep.

Journal ArticleDOI
TL;DR: It is found that the prevalence rates for chronic pain do vary with age and that the middle-aged group may be a high-risk group of patients with chronic pain.
Abstract: Objectives To describe age differences in chronic pain and to evaluate for differences in demographic and health-related variables among younger (18-39 years), middle-aged (40-59 years), and older adults (60-81 years) who reported chronic pain. Methods A total of 4000 Norwegian citizens were mailed a questionnaire that measured pain, quality of life, mood, and demographic and health-related variables. Results Of the total sample (n = 1912), 19.2% of the younger age group, 27.5% of the middle-aged group, and 31.2% of the older group reported chronic pain (ie, >3 months duration). A total of 58.9% of the participants in chronic pain reported having a chronic disease, with the most common being musculoskeletal problems, chronic pain disorder, and osteoarthritis. Participants in the older age group reported pain of longer duration and more comorbidities and received pain treatment more often. They had higher total quality of life scores, were more satisfied with their material comforts and social life, and reported better mood. The middle-aged group reported the largest number of pain locations, reported having fibromyalgia more frequently, and reported that the cause of their pain was not known. They were less satisfied with their social life than the older age group. The younger age group reported the highest rates of injury and accidents as the cause of their pain, and almost 43% of this age group was not receiving any treatment of their chronic pain. Conclusion This study found that the prevalence rates for chronic pain do vary with age and that the middle-aged group may be a high-risk group of patients with chronic pain.

Journal ArticleDOI
TL;DR: This study corroborates the importance of treatment expectation before entering a cognitive-behavioral intervention in patients with chronic musculoskeletal pain and assesses determinants of patients' treatment expectancy.
Abstract: Patients' initial beliefs about the success of a given pain treatment are shown to have an important influence on the final treatment outcome. The aims of the paper are to assess determinants of patients' treatment expectancy and to examine the extent to which treatment expectancy predicts the short-term and long-term outcome of cognitive-behavioral treatment of chronic pain. This study employs the data of 2 pooled randomized clinical trials evaluating the effectiveness of cognitive-behavioral interventions for 171 patients with fibromyalgia and chronic low back pain. Pretreatment and posttreatment expectancy were measured by a short questionnaire, which was based on the procedure by Borkovec and Nau. Four composite outcome variables (pain coping and control, motoric behavior, negative affect, and quality of life) were measured before and after the intervention and at 12 months follow-up. Furthermore, several patient characteristics were taken into account. Patients with higher treatment expectancies significantly received less disability compensation and were less fearful. A regression model of 3 factors (better pain coping and control, active and positive interpretation of pain, and less disability compensation) significantly explained 10% of the variance in pretreatment expectancy. Pretreatment expectancy significantly predicted each of the 4 outcome measures immediately after treatment and at 12 months follow-up. This study corroborates the importance of treatment expectation before entering a cognitive-behavioral intervention in patients with chronic musculoskeletal pain.

Journal ArticleDOI
01 Feb 2005-Sleep
TL;DR: Pregabalin appears to have an effect on sleep and sleep architecture that distinguishes it from benzodiazepines, and Enhancement of slow-wave sleep is intriguing.
Abstract: Study objectives To assess the effects of pregabalin compared with alprazolam and placebo on aspects of sleep in healthy volunteers. Design Randomized, double-blind, placebo- and active-controlled, 3-way crossover. Setting Single research center. Participants and interventions Healthy adult (12 men) volunteers (N=24) received oral pregabalin 150 mg t.i.d., alprazolam 1 mg t.i.d., and placebo t.i.d. for 3 days. Measurements and results Objective sleep was measured by an 8-channel polysomnograph; subjective sleep was measured using the Leeds Sleep Evaluation Questionnaire. Compared with placebo, pregabalin significantly increased slow-wave sleep both as a proportion of the total sleep period and the duration of stage 4 sleep. Alprazolam significantly reduced slow-wave sleep. Pregabalin and alprazolam produced modest, but significant, reductions in sleep-onset latency compared with placebo. Rapid eye movement sleep latency after pregabalin was no different than placebo but was significantly shorter than that found with alprazolam. Although there were no differences between the active treatments, both pregabalin and alprazolam reduced rapid eye movement sleep as a proportion of the total sleep period compared with placebo. Pregabalin also significantly reduced the number of awakenings of more than 1 minute in duration. Leeds Sleep Evaluation Questionnaire ratings of the ease of getting to sleep and the perceived quality of sleep were significantly improved following both active treatments, and ratings of behavior following awakening were significantly impaired by both drug treatments. Conclusions Pregabalin appears to have an effect on sleep and sleep architecture that distinguishes it from benzodiazepines. Enhancement of slow-wave sleep is intriguing, since reductions in slow-wave sleep have frequently been reported in fibromyalgia and general anxiety disorder.

Journal ArticleDOI
TL;DR: Among women with FM, pain symptoms early in the day are associated with variations in function of the hypothalamic-pituitary-adrenal axis, and cortisol levels alone explained 38% and 14% of the variation in pain at the waking and 1 hour time points, respectively.
Abstract: Objective To compare the momentary association between salivary cortisol levels and pain, fatigue, and stress symptoms in patients with fibromyalgia (FM), and to compare diurnal cycles of cortisol secretion in patients with FM and healthy control subjects in a naturalistic environment. Methods Twenty-eight patients with FM and 27 healthy control subjects completed assessments on salivary cortisol levels and pain, fatigue, and stress symptoms, 5 times a day for 2 consecutive days, while engaging in usual daily activities. Only those participants who adhered to the protocol (assessed via activity monitor) were included in the final analyses. Results Twenty FM patients and 16 healthy control subjects adhered to the protocol. There were no significant differences in cortisol levels or diurnal cortisol variation between FM patients and healthy controls. Among women with FM, a strong relationship between cortisol level and current pain symptoms was observed at the waking time point (t = 3.35, P = 0.008) and 1 hour after waking (t = 2.97, P = 0.011), but not at the later 3 time points. This association was not due to differences in age, number of symptoms of depression, or self-reported history of physical or sexual abuse. Cortisol levels alone explained 38% and 14% of the variation in pain at the waking and 1 hour time points, respectively. No relationship was observed between cortisol level and fatigue or stress symptoms at any of the 5 time points. Conclusion Among women with FM, pain symptoms early in the day are associated with variations in function of the hypothalamic–pituitary–adrenal axis.

Journal ArticleDOI
TL;DR: This is the first population study to demonstrate that those with established, and those psychologically at risk of, chronic widespread pain demonstrate abnormalities of HPA axis function, which are more marked in the former group.
Abstract: In clinic studies, altered hypothalamic-pituitary-adrenal (HPA) axis function has been associated with fibromyalgia, a syndrome characterised by chronic widespread body pain These results may be explained by the associated high rates of psychological distress and somatisation We address the hypothesis that the latter, rather than the pain, might explain the HPA results A population study ascertained pain and psychological status in subjects aged 25 to 65 years Random samples were selected from the following three groups: satisfying criteria for chronic widespread pain; free of chronic widespread pain but with strong evidence of somatisation ('at risk'); and a reference group HPA axis function was assessed from measuring early morning and evening salivary cortisol levels, and serum cortisol after physical (pain pressure threshold exam) and chemical (overnight 025 mg dexamethasone suppression test) stressors The relationship between HPA function with pain and the various psychosocial scales assessed was modelled using appropriate regression analyses, adjusted for age and gender In all 131 persons with chronic widespread pain (participation rate 74%), 267 'at risk' (58%) and 56 controls (70%) were studied Those in the chronic widespread pain and 'at risk' groups were, respectively, 31 (95% CI (13, 73)) and 18 (08, 40) times more likely to have a saliva cortisol score in the lowest third None of the psychosocial factors measured were, however, associated with saliva cortisol scores Further, those in the chronic widespread pain (19 (08, 47)) and 'at risk' (16 (07, 36)) groups were also more likely to have the highest serum cortisol scores High post-stress serum cortisol was related to high levels of psychological distress (p = 005, 95% CI (002, 008)) After adjusting for levels of psychological distress, the association between chronic widespread pain and post-stress cortisol scores remained, albeit slightly attenuated This is the first population study to demonstrate that those with established, and those psychologically at risk of, chronic widespread pain demonstrate abnormalities of HPA axis function, which are more marked in the former group Although some aspects of the altered function are related to the psychosocial factors measured, we conclude that the occurrence of HPA abnormality in persons with chronic widespread pain is not fully explained by the accompanying psychological stress

Journal ArticleDOI
TL;DR: Positive health-related outcomes in this mostly unresponsive condition can be obtained with a low-cost, group multidisciplinary intervention in a community-based, nonclinical setting.
Abstract: Objectives To assess the effectiveness of multidisciplinary rehabilitation in the treatment of fibromyalgia in comparison to standard medical care. Methods Seventy-nine men and women were randomly assigned to one of two groups. The intervention group consisted of a rheumatologist and physical therapist intake and discharge, 18 group supervised exercise therapy sessions, 2 group pain and stress management lectures, 1 group education lecture, 1 group dietary lecture, and 2 massage therapy sessions. The control group consisted of standard medical care with the patients' family physician. Outcome measures included self-perceived health status, pain-related disability, average pain intensity, depressed mood, days in pain, hours in pain, prescription and nonprescription medication usage, and work status. Outcomes were measured at the end of the 6-week intervention and at 15-month follow-up. Results Thirty-five out of 43 patients from the intervention group and 36 out of 36 patients from the control group completed the study. There were no statistically significant differences between the 2 groups prior to intervention. Intention-to-treat analysis revealed that the intervention group, in comparison to the control group, experienced statistically significant changes at intervention completion in self-perceived health status, average pain intensity, pain related disability, depressed mood, days in pain, and hours in pain, but no significant differences in nonprescription drug use, prescription drug use, or work status. At 15 months, all health outcomes retained their significance except health status. Nonprescription and prescription drug use demonstrated significant reductions at 15 months. Binary logistic regression indicated that long-term changes in Pain Disability Index were influenced by long-term exercise adherence and income status. Conclusions Positive health-related outcomes in this mostly unresponsive condition can be obtained with a low-cost, group multidisciplinary intervention in a community-based, nonclinical setting.

Journal ArticleDOI
TL;DR: The aim of the present study was to assess, compare, and correlate the pain response to an experimental pain stimulus, the pain intensity of the habitual pain, and quality of life parameters in groups of females with chronic non‐malignant pain syndromes.

Journal ArticleDOI
TL;DR: Fibromyalgia patients experienced short-term benefits in psychological and health variables through emotional expression of personal traumatic experiences through written expression of traumatic experiences in a randomized, controlled trial.
Abstract: Objective Written expression of traumatic experiences, an intervention found to have health benefits in rheumatoid arthritis, asthma, and breast cancer, was tested in a randomized, controlled trial with female fibromyalgia patients. It was hypothesized that relative to controls, patients engaging in the writing intervention would experience improved status on psychological well-being and physical health variables. Methods Patients (N = 92) were randomized into a trauma writing group, a control writing group, or usual care control group. The two writing groups wrote in the laboratory for 20 minutes on 3 days at 1-week intervals. Psychological well-being, pain, and fatigue were the primary outcome variables. Assessments were made at pretreatment, posttreatment, 4-month follow-up, and 10-month follow-up. Results The trauma writing group experienced significant reductions in pain (effect size [ES] = 0.49) and fatigue (ES = 0.62) and better psychological well-being (ES = 0.47) at the 4-month follow-up relative to the control groups. Benefits were not maintained at the 10-month follow-up. Conclusion Fibromyalgia patients experienced short-term benefits in psychological and health variables through emotional expression of personal traumatic experiences.

Journal ArticleDOI
01 Jun 2005-Pain
TL;DR: It was demonstrated that depression and poor sleep are associated with a reduced pain threshold and these relationships persisted after adjustment for pain status.
Abstract: To determine the relative contributions of psychological factors and sleep disturbance to reduced pain threshold we conducted a cross-sectional two-phase population-based study. A total of 424 subjects were recruited, stratified by pain and distress status. Subjects completed a postal questionnaire that asked about current pain and covered aspects of psychological status and sleep disturbance. Samples of subjects stratified by the extent of bodily pain they reported and psychological status were invited to participate in an examination of pain threshold. The association between psychological status, sleep disturbance and a low pain threshold was examined using ordinal regression. High levels of psychological distress (OR=1.6, 95% CI (1.02, 2.5)), disturbed sleep (OR=2.2, 95% CI (1.4, 3.5)) and high scores on the HAD depression scale (OR=2.1, 95% CI (1.3, 3.2)) were all associated with having a low pain threshold. In multivariate analysis disturbed sleep and depression remained independently associated with a low pain threshold. These relationships persisted after adjustment for pain status. This study had demonstrated that depression and poor sleep are associated with a reduced pain threshold.

Journal ArticleDOI
TL;DR: Malondialdehyde levels were significantly higher and superoxide dismutase levels significantly lower in fibromyalgic patients than controls and these findings may support the hypothesis of fibromyalgia as an oxidative disorder.
Abstract: The role of free radicals in fibromyalgia is controversial. In this study, 85 female patients with primary fibromyalgia and 80 age-, height-, and weight-matched healthy women were evaluated for oxidant/antioxidant balance. Malondialdehyde is a toxic metabolite of lipid peroxidation used as a marker of free radical damage. Superoxide dismutase is an intracellular antioxidant enzyme and shows antioxidant capacity. Pain was assessed by visual analog scale. Tender points were assessed by palpation. Age, smoking, body mass index (BMI), and duration of disease were also recorded. Malondialdehyde levels were significantly higher and superoxide dismutase levels significantly lower in fibromyalgic patients than controls. Age, BMI, smoking, and duration of disease did not affect these parameters. We found no correlation between pain and number of tender points. In conclusion, oxidant/antioxidant balances were changed in fibromyalgia. Increased free radical levels may be responsible for the development of fibromyalgia. These findings may support the hypothesis of fibromyalgia as an oxidative disorder.

Journal ArticleDOI
TL;DR: This meta-analysis provides strong evidence that some patients with LB have fatigue, musculoskeletal pain, and neurocognitive difficulties that may last for years despite antibiotic treatment.
Abstract: symptoms listed above that compared patients who had had LB with controls from the general population. Five studies with 504 patients and 530 controls were included in the meta-analysis. Results The prevalence of symptoms was significantly higher in the LB patients, with P-values between � 0.00001 and 0.007 for 8 of the 10 symptoms in the three categories listed above. The higher prevalence of certain neurocognitive symptoms but not others, in the same pattern as reported in the literature, is further confirmation of this syndrome. The pattern of symptoms appears to be different from that seen in fibromyalgia, depression, and chronic fatigue syndrome. Conclusions This meta-analysis provides strong evidence that some patients with LB have fatigue, musculoskeletal pain, and neurocognitive difficulties that may last for years despite antibiotic treatment.

Journal ArticleDOI
TL;DR: Sleep disordered breathing (SDB) increases markedly at menopause for reasons that include both weight gain and unclear hormonal mechanisms, so health care providers should not assume sleep complaints are due to vasomotor related insomnia/depression without considering SDB.
Abstract: Sleep difficulty is one of the hallmarks of menopause. Following recent studies showing no cardiac benefit and increased breast cancer, the question of indications for hormonal therapy has become even more pertinent. Three sets of sleep disorders are associated with menopause: insomnia/depression, sleep disordered breathing and fibromyalgia. The primary predictor of disturbed sleep architecture is the presence of vasomotor symptoms. This subset of women has lower sleep efficiency and more sleep complaints. The same group is at higher risk of insomnia and depression. The "domino theory" of sleep disruption leading to insomnia followed by depression has the most scientific support. Estrogen itself may also have an antidepressant as well as a direct sleep effect. Treatment of insomnia in responsive individuals may be a major remaining indication for hormone therapy. Sleep disordered breathing (SDB) increases markedly at menopause for reasons that include both weight gain and unclear hormonal mechanisms. Due to the general under-recognition of SDB, health care providers should not assume sleep complaints are due to vasomotor related insomnia/depression without considering SDB. Fibromyalgia has gender, age and probably hormonal associations. Sleep complaints are almost universal in FM. There are associated polysomnogram (PSG) findings. FM patients have increased central nervous system levels of the nociceptive neuropeptide substance P (SP) and lower serotonin levels resulting in a lower pain threshold to normal stimuli. High SP and low serotonin have significant potential to affect sleep and mood. Treatment of sleep itself seems to improve, if not resolve FM. Menopausal sleep disruption can exacerbate other pre-existing sleep disorders including RLS and circadian disorders.

Journal ArticleDOI
TL;DR: Chronic myalgia may not improve until the underlying precipitating or perpetuating factor(s) are themselves managed, and sometimes, correction of an underlying cause of myalgia is all that is needed to resolve the condition.
Abstract: Chronic muscle pain (myalgia) is a common problem throughout the world. Seemingly simple, it is actually a difficult problem for the clinician interested in determining the aetiology of the pain, as well as in managing the pain. The two common muscle pain conditions are fibromyalgia and myofascial pain syndrome. Fibromyalgia is a chronic, widespread muscle tenderness syndrome, associated with central sensitisation. It is often accompanied by chronic sleep disturbance and fatigue, visceral pain syndromes like irritable bowel syndrome and interstitial cystitis. Myofascial pain syndrome is an overuse or muscle stress syndrome characterised by the presence of trigger points in muscle. The problem these syndromes pose lies not in making the diagnosis of muscle pain. Rather, it is the need to identify the underlying cause(s) of persistent or chronic muscle pain in order to develop a specific treatment plan. Chronic myalgia may not improve until the underlying precipitating or perpetuating factor(s) are themselves managed. Precipitating or perpetuating causes of chronic myalgia include structural or mechanical causes like scoliosis, localised joint hypomobility, or generalised or local joint laxity; and metabolic factors like depleted tissue iron stores, hypothyroidism or Vitamin D deficiency. Sometimes, correction of an underlying cause of myalgia is all that is needed to resolve the condition.