The abstracts in this collection are intended to provide doctors and other health professionals with a convenient overview of trends in research on fibromyalgia published in medical journals in the year 2010. The studies were selected from the extensive literature on fibromyalgia so as to cover a wide range of subjects in limited space.

The following studies were published in the period January through June, 2010, and others will be added to this selection at intervals during the year. Similar collections of abstracts produced annually from 1999 on can be found on the website of the National Fibromyalgia Partnership: www.fmpartnership.org.

The abstracts are arranged in alphabetical order by lead author.

Exercise alters pain sensitivity in Gulf War veterans with chronic musculoskeletal pain

Since returning from the Persian Gulf, nearly 100,000 veterans of the first Gulf War (GVs) have reported numerous symptoms with no apparent medical explanation. A primary complaint of these individuals is chronic musculoskeletal pain (CMP). CMP symptoms in GVs are similar to those reported by patients with fibromyalgia (FM), but have not received equivalent scientific attention. Exercise research in CMP patients suggests that acute exercise may exacerbate pain while chronic exercise can reduce pain and improve other symptoms. However, the influence of exercise on GVs with CMP is largely unexplored. This study examined the impact of an acute bout of exercise on pain sensitivity in GVs with CMP. Thirty-two GVs (CMP, n = 15; Control, n = 17) were recruited to complete a series of psychophysical assessments to determine pain sensitivity to heat and pressure stimuli before and after exercise. In response to heat-pain stimuli, GVs with CMP reported higher pain intensity and affect ratings than healthy GVs and exhibited a significant increase in ratings following exercise. GVs with CMP rated exercise as more painful and effortful and were generally more sensitive to heat-pain stimuli than healthy GVs. These results are similar to what has been reported for acute exercise in patients with FM. PERSPECTIVE: Gulf War veterans with CMP perceive exercise as more painful and effortful than healthy GVs and experience increased pain sensitivity following exercise. These results suggest that similar abnormalities in central nervous system processing of nociceptive information documented in FM may also be occurring in GVs with CMP.

J Pain. 2010 Mar 23. [Epub ahead of print]

Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease

INTRODUCTION: Fibromyalgia is a chronic pain syndrome with unknown etiology. Recent studies have shown some evidence demonstrating that oxidative stress may have a role in the pathophysiology of fibromyalgia. However, it is still not clear whether oxidative stress is the cause or the effect of the abnormalities documented in fibromyalgia. Furthermore, the role of mitochondria in the redox imbalance reported in fibromyalgia also is controversial. We undertook this study to investigate the role of mitochondrial dysfunction, oxidative stress, and mitophagy in fibromyalgia. METHODS: We studied 20 patients (2 male, 18 female patients) from the database of the Sevillian Fibromyalgia Association and 10 healthy controls. We evaluated mitochondrial function in blood mononuclear cells from fibromyalgia patients measuring, coenzyme Q10 levels with high-performance liquid chromatography (HPLC), and mitochondrial membrane potential with flow cytometry. Oxidative stress was determined by measuring mitochondrial superoxide production with MitoSOX and lipid peroxidation in blood mononuclear cells and plasma from fibromyalgia patients. Autophagy activation was evaluated by quantifying the fluorescence intensity of LysoTracker Red staining of blood mononuclear cells. Mitophagy was confirmed by measuring citrate synthase activity and electron microscopy examination of blood mononuclear cells. RESULTS: We found reduced levels of coenzyme Q10, decreased mitochondrial membrane potential, increased levels of mitochondrial superoxide in blood mononuclear cells, and increased levels of lipid peroxidation in both blood mononuclear cells and plasma from fibromyalgia patients. Mitochondrial dysfunction was also associated with increased expression of autophagic genes and the elimination of dysfunctional mitochondria with mitophagy. CONCLUSIONS: These findings may support the role of oxidative stress and mitophagy in the pathophysiology of fibromyalgia.

Arthritis Res Ther. 2010 Jan 28; 12(1):R17. [Epub ahead of print]

Effects of lifestyle physical activity on perceived symptoms and physical function in adults with fibromyalgia: results of a randomized trial

INTRODUCTION: Although exercise is therapeutic for adults with fibromyalgia (FM), its symptoms often create obstacles that discourage exercise. We evaluated the effects of accumulating at least 30 minutes of self-selected lifestyle physical activity (LPA) on perceived physical function, pain, fatigue, body mass index, depression, tenderness, and the six-minute walk test in adults with FM. METHODS: Eighty-four minimally active adults with FM were randomized to either LPA or a FM education control (FME) group. LPA participants worked toward accumulating 30 minutes of self-selected moderate-intensity LPA, five to seven days per week, while the FME participants received information and support. RESULTS: Seventy-three of the 84 participants (87%) completed the 12-week trial. The LPA group increased their average daily steps by 54%. Compared to FME, the LPA group reported significantly less perceived functional deficits (P = .032) and less pain (P = .006). There were no differences between the groups on the six-minute walk test (P = .067), fatigue, depression, body mass index, or tenderness. CONCLUSIONS: Accumulating 30 minutes of LPA throughout the day produces clinically relevant changes in perceived physical function and pain in previously minimally active adults with FM.

Arthritis Res Ther. 2010 Mar 30;12(2):R55. [Epub ahead of print]

Contributions of change in clinical status parameters to Patient Global Impression of Change (PGIC) scores among persons with fibromyalgia treated with milnacipran

Clinical trials on the treatment of pain syndromes have adopted Patient Global Impression of Change (PGIC) as a primary outcome. However, little is known about how change in clinical status influences these ratings. The present study examined relationships between changes in pain, depressed mood, physical functioning, vitality, sleep disturbance, cognitive complaints, and PGIC ratings among 1260 participants with fibromyalgia (FM) who completed one of two trials examining the safety and efficacy of milnacipran. Many of the relationships between change in clinical status and PGIC ratings were stronger among persons who rated themselves as improved (responders) versus those reporting no change or a worsening of their condition (non-responders). Among non-responders, simultaneous regression analysis revealed that greater degrees of depressed mood and pain, and poorer physical function were significantly associated with worse PGIC ratings. Among responders, improvements in pain were significantly associated with better PGIC ratings, along with improvements in vitality, sleep, physical function, and cognitive complaints. These findings underscore the complexity of global ratings in FM patients, and suggest the association between clinical status and PGIC ratings varies as a function of perceived treatment response. Several domains were associated with PGIC ratings, highlighting the need to assess multiple outcomes in clinical trials of treatments for FM.

Pain. 2010 Mar 22. [Epub ahead of print]

Deviations in the endocrine system and brain of patients with fibromyalgia: cause or consequence of pain and associated features?

The brain and endocrine system are crucial interfaces responding to pathological and psychological processes. This review discusses whether endocrine deviations and structural and functional changes in the brain are a cause or consequence of fibromyalgia. Studies in patients with fibromyalgia virtually uniformly observed subtle alterations in hypothalamic pituitary adrenal functioning, hyporeactive autonomic nervous system responsiveness to stressors, and structural and functional changes in the brain. Our model proposes that predisposing factors, such as genetic vulnerability and trauma, have led to an alteration of the nociceptive system including several neuroendocrine changes. The resulting pain and associated symptoms, such as sleep disturbance, low fitness, fatigue, stress, and distress, are a cause of new neuroendocrine changes. The model predicts that favorable neuroendocrine changes are to be expected after successful pharmacological or non-pharmacological interventions that target pain and associated symptoms.

Ann N Y Acad Sci. 2010 Apr; 1193(1):98–110

Comparative efficacy and harms of duloxetine, milnacipran, and pregabalin in fibromyalgia syndrome

Duloxetine (DLX), milnacipran (MLN), and pregabalin (PGB) are the only drugs licensed by the US Food and Drug Administration (FDA) for fibromyalgia syndrome (FMS). Evidence on the comparative benefits and harms is still accruing. The authors searched MEDLINE, SCOPUS, Cochrane Central Register of Controlled Trials, and sought unpublished data from the databases of FDA, US National Institutes for Health, and Industry through May 2009 for randomized controlled trials. Outcomes of interest were symptom reduction (pain, fatigue, sleep disturbance, depressed mood, reduced health-related quality of life), and adverse events. 17 studies with 7,739 patients met the inclusion criteria. The 3 drugs were superior to placebo except DLX for fatigue, MLN for sleep disturbance, and PGB for depressed mood. Adjusted indirect comparisons indicated no significant differences for 30% pain relief and dropout rates due to adverse events between the 3 drugs. Significant differences in average symptom reduction were found: DLX and PGB were superior to MLN in reduction of pain and sleep disturbances. DLX was superior to MLN and PGB in reducing depressed mood. MLN and PGB were superior to DLX in reducing fatigue. The risk of headache and nausea with DLX and MLN was higher compared with PGB. The risk of diarrhea was higher with DLX compared to MLN and PGB. There is evidence for the short-term (up to 6 months) efficacy of DLX, MLN, and PGB. Differences with regard to the occurrence of the key symptoms of FMS and to drug-specific adverse events may be relevant for the choice of medication. PERSPECTIVE: This article presents comparative data on the efficacy and harms of duloxetine, milnacipran, and pregabalin in fibromyalgia syndrome. The results can help clinicians in choosing medication since the 3 drugs have different effects on the key symptoms of fibromyalgia syndrome and differences in side effects, contraindications, and warnings.

Copyright (c) 2010 American Pain Society. Published by Elsevier Inc. All rights reserved. J Pain. 2010 Jun; 11(6):505–21. Epub 2010 Apr 24

Sustained pain reduction through affective self-awareness in fibromyalgia: a randomized controlled trial

BACKGROUND AND OBJECTIVE: Affect and how it is regulated plays a role in pain perception, maintenance of pain, and its resolution. This randomized, controlled trial evaluated an innovative affective self-awareness (ASA) intervention, which was designed to reduce pain and improve functioning in individuals with fibromyalgia. PARTICIPANTS AND METHODS: Forty-five women with fibromyalgia were randomized to a manualized ASA intervention (n = 24) or wait-list control (n = 21). The intervention began with a one-time physician consultation, followed by 3 weekly, 2-h group sessions based upon a mind-body model of pain. Sessions focused on structured written emotional disclosure and emotional awareness exercises. Outcomes in both conditions were measured by a blinded assessor at baseline, post-intervention, and 6-month follow-up. MEASURES: The primary outcome was pain severity (Brief Pain Inventory); secondary outcomes included tender-point threshold and physical function (SF-36 Physical Component Summary). Intent-to-treat analyses compared groups on outcomes using analysis of covariance and on the proportion of patients achieving >/=30% and >/=50% pain reduction at 6 months. RESULTS: Adjusting for baseline scores, the intervention group had significantly lower pain severity (p < 0.001), higher self-reported physical function (p < 0.001), and higher tender-point threshold (p = 0.02) at 6 months compared to the control group. From baseline to 6 months, 45.8% of the ASA intervention group had >/=30% reduction in pain severity, compared to none of the controls (p < 0.001). CONCLUSIONS: The affective self-awareness intervention improved pain, tenderness, and self-reported physical function for at least 6 months in women with fibromyalgia compared to wait-list control. This study suggests the value of interventions targeting emotional processes in fibromyalgia, although further studies should evaluate the efficacy of this intervention relative to active controls.

Lack of understanding in fibromyalgia and rheumatoid arthritis: the Illness Invalidation Inventory (3*I)

BACKGROUND: Patients with rheumatic diseases may face "discounting" (denying and patronising) or "lack of understanding" because of having symptoms without external clinical signs, but instruments to assess such invalidation experiences are lacking. OBJECTIVES: To develop and evaluate the Illness Invalidation Inventory (3*I), to compare invalidation experiences of two groups of patients who differ in visual signs and laboratory findings—rheumatoid arthritis (RA) and fibromyalgia—and to examine the association of invalidation with health status. METHODS: A questionnaire (eight items with respect to five sources: spouse, family, medical professionals, work environment and social services) was constructed. It was completed by 142 patients with RA and 167 patients with fibromyalgia. RESULTS: Principal axis factoring with oblimin rotation yielded two factors with high internal consistency (alpha>0.70): "discounting" (five items) and "lack of understanding" (three items). Patients with fibromyalgia experienced significantly more discounting and lack of understanding from their family, medical professionals, colleagues and social services than did patients with RA. Both patient groups experienced more invalidation from social services, colleagues and family than from medical professionals and spouses. More discounting and lack of understanding correlated with poorer mental well-being and social functioning in both patient groups. Discounting correlated with more physical disability and pain in patients with RA. CONCLUSIONS: The 3*I is a brief, reliable instrument for assessing patients’ perceptions of invalidation from different sources, which differ between patient groups and are associated with health status. Future validation research should clarify the clinical impact of invalidation on treatment adherence and outcome.

Fascia: A missing link in our understanding of the pathology of fibromyalgia

Significant evidence exists for central sensitization in fibromyalgia, however the cause of this process in fibromyalgia—and how it relates to other known abnormalities in fibromyalgia—remains unclear. Central sensitization occurs when persistent nociceptive input leads to increased excitability in the dorsal horn neurons of the spinal cord. In this hyperexcited state, spinal cord neurons produce an enhanced responsiveness to noxious stimulation, and even to formerly innocuous stimulation. No definite evidence of muscle pathology in fibromyalgia has been found. However, there is some evidence for dysfunction of the intramuscular connective tissue, or fascia, in fibromyalgia. This paper proposes that inflammation of the fascia is the source of peripheral nociceptive input that leads to central sensitization in fibromyalgia. The fascial dysfunction is proposed to be due to inadequate growth hormone production and HPA axis dysfunction in fibrmyalgia. Fascia is richly innervated, and the major cell of the fascia, the fibroblast, has been shown to secrete pro-inflammatory cytokines, particularly IL-6, in response to strain. Recent biopsy studies using immuno-histochemical staining techniques have found increased levels of collagen and inflammatory mediators in the connective tissue surrounding the muscle cells in fibromyalgia patients. The inflammation of the fascia is similar to that described in conditions such as plantar fasciitis and lateral epicondylitis, and may be better described as a dysfunctional healing response. This may explain why NSAIDs and oral steroids have not been found effective in fibromyalgia. Inflammation and dysfunction of the fascia may lead to central sensitization in fibromyalgia. If this hypothesis is confirmed, it could significantly expand treatment options to include manual therapies directed at the fascia such as Rolfing and myofascial release, and direct further research on the peripheral pathology in fibromyalgia to the fascia.

J Bodyw Mov Ther. 2010 Jan;14(1):3–12

Fibromyalgia: moderate and substantial pain intensity reduction predicts improvement in other outcomes and substantial quality of life gain

Chronic pain is associated with a range of other problems, including disturbed sleep, depression, anxiety, fatigue, reduced quality of life, and an inability to work or socialise. We investigated whether good symptom control of pain (using definitions of moderate and substantial benefit) is associated with improvement in other symptoms. Individual patient data from four randomised trials in fibromyalgia (2575 patients) lasting 8–14weeks were used to calculate percentage pain reduction for each completing patient (1858), divided into one of five groups according to pain reduction, irrespective of treatment: substantial benefit – 50% pain reduction; moderate – 30% to <50%; minimal – 15% to <30%; marginal – 0% to <15%; worse – <0% (increased pain intensity). We then calculated change from baseline to end of trial for measures of fatigue, function, sleep, depression, anxiety, ability to work, general health status, and quality-adjusted life year (QALY) gain over a 12-month period. Substantial and moderate pain intensity reductions were associated with statistically significant reduction from baseline by end of trial in all measures, with values by trial end at or approaching normative values. Substantial pain intensity reduction resulted in 0.11 QALYs gained, and moderate pain intensity reduction in 0.07 QALYs gained over a 12-month period. Substantial and moderate pain intensity reduction predicts broad beneficial outcomes and improved quality of life that do not occur without pain relief. Pain intensity reduction is a simple and effective predictor of which patients should continue treatment, and which should discontinue and try an alternative therapy.

Pain. 2010 Mar 25. [Epub ahead of print]

Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity

OBJECTIVE:: Fibromyalgia (FM) is considered to be the prototypical central chronic pain syndrome and is associated with widespread pain that fluctuates spontaneously. Multiple studies have demonstrated altered brain activity in these patients. Our objective was to investigate the degree of connectivity between multiple brain networks in FM, as well as how activity in these networks correlates with spontaneous pain. METHODS: Resting functional magnetic resonance imaging (fMRI) data in FM patients (n=18) and age-matched healthy controls (HC, n=18) were analyzed using dual regression independent component analysis (ICA)—a data driven approach used to identify independent brain networks. We evaluated intrinsic, or resting, connectivity in multiple brain networks: the default mode network (DMN), the executive attention network (EAN), and the medial visual network (MVN), with the MVN serving as a negative control. Spontaneous pain levels were also covaried with intrinsic connectivity. RESULTS: We found that FM patients had greater connectivity within the DMN and right EAN (rEAN; p<0.05, corrected), and greater connectivity between the DMN and the insular cortex—a brain region known to process evoked pain. Furthermore, greater spontaneous pain at the time of the scan correlated with greater intrinsic connectivity between the insula and both the DMN and rEAN (p<0.05, corrected). CONCLUSION: Our findings indicate that resting brain activity within multiple networks is associated with spontaneous clinical pain in FM. These findings may also have broader implications for how subjective experiences such as pain arise from a complex interplay amongst multiple brain networks.

Arthritis Rheum. 2010 Apr 6. [Epub ahead of print]

Fibromyalgia syndrome is associated with hypocortisolism

BACKGROUND: Fibromyalgia syndrome (FMS) is a disease of unknown pathogenesis characterized by chronic musculoskeletal pain. FMS has been also associated with altered endocrinological responses, but findings are inconsistent. PURPOSE: The aim of the present study was to investigate free salivary cortisol levels in FMS patients compared with healthy controls with a particular focus on the cortisol awakening response (CAR). The saliva samples were collected in a controlled hospital-hotel setting, in which the participants' compliance was high and a number of potential confounders were analyzed. METHOD: Twenty-nine chronic female FMS patients and 29 age-matched healthy female controls were recruited. Salivary cortisol samples were investigated eight times: in the afternoon when participants arrived at the hospital, after stress provocation (to be reported separately), in the evening, before they went to sleep, upon awakening, 30 and 60 min later, and during the afternoon of the second day. Questionnaires measuring pain levels, sleeping problems, perceived stress, and personality were administered to the participants. Other psychophysiological measurements were used to assess sleep quality and heart rate. RESULTS: Patients with FMS had significantly lower cortisol levels during the day, most pronounced in the morning (CAR). The potential confounders analyzed did not influence the results. As expected, FMS patients reported more pain, stress, sleeping problems, anxiety, and depression. CONCLUSION: The results lend support to the hypothesis of a dysfunction in the hypothalamus-pituitary-adrenal axis in FMS patients, with generally lower cortisol values, most pronounced upon awakening (CAR).

Int J Behav Med. 2010 May 11. [Epub ahead of print]

Cognitive effects of pregabalin in healthy volunteers: a double-blind, placebo-controlled trial

BACKGROUND: Antiepileptic drugs (AEDs) can be associated with neurotoxic side effects including cognitive dysfunction, a problem of considerable importance given the usual long-term course of treatment. Pregabalin is a relatively new AED widely used for the treatment of seizures and some types of chronic pain including fibromyalgia. We measured the cognitive effects of 12 weeks of pregabalin in healthy volunteers. METHODS: Thirty-two healthy volunteers were randomized in a double-blind parallel study to receive pregabalin or placebo (1:1). Pregabalin was titrated over 8 weeks to 600 mg/d. At baseline, and after 12 weeks of treatment, all subjects underwent cognitive testing. Test-retest changes in all cognitive and subjective measures were Z scored against test-retest regressions previously developed from 90 healthy volunteers. Z scores from the placebo and pregabalin groups were compared using Wilcoxon tests. RESULTS: Thirty subjects completed the study (94%). Three of 6 target cognitive measures (Digit Symbol, Stroop, Controlled Oral Word Association) revealed significant test-retest differences between the pregabalin and placebo groups, all showing negative effects with pregabalin (p < 0.05). These cognitive effects were paralleled by complaints on the Portland Neurotoxicity Scale, a subjective measure of neurotoxicity (p < 0.01). CONCLUSION: At conventional doses and titration, pregabalin induced mild negative cognitive effects and neurotoxicity complaints in healthy volunteers. These effects are one factor to be considered in the selection and monitoring of chronic AED therapy. Class of Evidence: This study provides Class I evidence that pregabalin 300 mg BID negatively impacts cognition on some tasks in healthy volunteers.

Neurology. 2010 Mar 2; 74(9):755–61

Self-regulatory deficits in fibromyalgia and temporomandibular disorders

Chronic pain conditions such as fibromyalgia (FM) and temporomandibular disorders (TMDs) are accompanied by complex interactions of cognitive, emotional, and physiological disturbances. Such conditions are complicated and draining to live with, and successful adaptation may depend on ability to self-regulate. Self-regulation involves capacity to exercise control and guide or alter reactions and behavior, abilities essential for human adjustment. Research indicates that self-regulatory strength is a limited source that can be depleted or fatigued, however, and the current study aimed to show that patients with FM and TMD are vulnerable to self-regulatory fatigue as a consequence of their condition. Patients (N=50) and pain-free matched controls (N=50) were exposed to an experimental self-regulation task followed by a persistence task. Patients displayed significantly less capacity to persist on the subsequent task compared with controls. In fact, patients exposed to low self-regulatory effort displayed similar low persistence to patients and controls exposed to high self-regulatory effort, indicating that patients with chronic pain conditions may be suffering from chronic self-regulatory fatigue. Baseline heart rate variability, blood glucose, and cortisol predicted persistence, more so for controls than for patients, and more so in the low vs. high self-regulation condition. Impact of chronic pain conditions on self-regulatory effort was mediated by pain, but not by any other factors. The current study suggests that patients with chronic pain conditions likely suffer from chronic self-regulatory fatigue, and underlines the importance of taking self-regulatory capacity into account when aiming to understand and treat these complex conditions.

Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. Pain. 2010 Jun 17. [Epub ahead of print]

Pain variability in fibromyalgia is related to activity and rest: role of peripheral tissue impulse input

Because fibromyalgia (FM) patients frequently report activity-dependent deep tissue pains, impulse input from painful body regions may be relevant for their musculoskeletal complaints. In addition, peripheral impulse input may induce and maintain thermal and mechanical hyperalgesia of FM patients. If so, activity and rest may alternately enhance and diminish intensity of FM pain. However, the effects of exercise on pain are ambiguous in studies of FM. Whereas exercise-only studies demonstrated increased pain and hyperalgesia during and after physical activity, some exercise studies that included rest periods resulted in decreased FM pain and increased function. To further clarify these effects, we examined the effects of alternating exercise with rest on clinical pain and thermal/mechanical hyperalgesia of 34 FM patients and 36 age-matched healthy controls (NC). Using an ergometer, all subjects performed arm exercise to exhaustion twice alternating with 15-minute rest periods. Although strenuous muscle activity was reported as painful by most FM subjects, overall clinical pain consistently decreased during the rest periods. Additionally, FM subjects’ pain sensitivity to mechanical pressure decreased after each exercise and rest session. CONCLUSION: Alternating strenuous exercise with brief rest periods not only decreased overall clinical pain of FM subjects but also their mechanical hyperalgesia. No prolonged worsening of overall FM pain and hyperalgesia occurred despite vigorous muscle activity. Our findings contribute further evidence that FM pain and hyperalgesia are at least partially maintained by muscle impulse input, and that some types of exercises may be beneficial for FM. PERSPECTIVE: FM is a pain-amplification syndrome that depends at least in part on peripheral tissue impulse input. Whereas muscle activity increased overall pain, short rest periods produced analgesic effects.

Copyright © 2010 American Pain Society. Published by Elsevier Inc. All rights reserved. J Pain. 2010 May 6. [Epub ahead of print]

Pharmacological treatment of fibromyalgia syndrome: new developments

Fibromyalgia is a chronic pain disorder characterized by widespread pain, stiffness, insomnia, fatigue and distress. Several randomized controlled trials (RCTs) have shown moderate effectiveness of pharmacological therapies for fibromyalgia pain. Evidence from these trials suggests that pharmacological therapy can not only improve pain but also fatigue, function and well-being in patients with fibromyalgia. Duloxetine and milnacipran, two highly selective serotonin-norepinephrine (noradrenaline) reuptake inhibitors, and the alpha(2) delta agonist pregabalin have been approved by the US FDA for the treatment of fibromyalgia symptoms. In general, about half of all treated patients seem to experience a 30% reduction of symptoms, suggesting that many patients with fibromyalgia will require additional therapies. Thus, other forms of treatment, including exercise, cognitive behavioural therapies and self-management strategies, may be necessary to achieve satisfactory treatment outcomes. Despite promising results of pilot trials, RCTs with dopamine receptor agonists and sodium channel antagonists have so far been disappointing for patients with fibromyalgia. However, new pharmacological approaches for the treatment of fibromyalgia pain and insomnia using sodium oxybate appear to be promising.

Drugs. 2010; 70(1):1–14

Pregabalin in fibromyalgia: meta-analysis of efficacy and safety from company clinical trial reports

.OBJECTIVES: Meta-analysis of pregabalin trials in FM using company trial reports, which provide more detailed information about trials than published papers. FM is a common condition with a significant impact on quality of life. METHODS: Reports of five high-quality randomized trials (3808 patients) of pregabalin in FM were obtained from Pfizer. Four trials (2754 patients) were of classical trial design and one was an enriched enrolment randomized withdrawal design. Outcomes for meta-analysis from the four trials with classical design were pooled in an intention-to-treat analysis. RESULTS: Significant benefit of pregabalin over placebo was seen for a variety of outcomes including mean pain and sleep scores, the proportion of patients achieving at least 50% pain relief and most of the individual domains of short-form 36. Only a minority of patients achieve moderate or substantial pain relief. The proportions of patients with any adverse event, somnolence or dizziness were also significantly greater with pregabalin than with placebo. There was no difference with regard to serious adverse events. A dose-response relationship was apparent for at least 50% pain relief and for adverse event outcomes. CONCLUSIONS: Pregabalin is effective in treating FM and is relatively safe. The size of therapeutic effect is similar to that with other recent interventions such as duloxetine and the combination of tramadol and paracetamol. Enriched enrolment randomized withdrawal design gives similar results to classical trial designs in FM.

Rheumatology (Oxford). 2010 Apr; 49(4):706–15. Epub 2010 Jan 7

Brain perfusion in fibromyalgia patients and its differences between responders and poor responders to gabapentin

INTRODUCTION: The aim of the present study was to determine the brain areas associated with fibromyalgia, and whether pretreatment regional cerebral blood flow (rCBF) can predict response to gabapentin treatment. METHODS: A total of 29 women with fibromyalgia and 10 healthy women (without pain) matched for age were finally enrolled in the study. Technetium-99m ethyl cysteinate dimer single photon emission computed tomography ((99m)Tc-ECD SPECT) was performed in the fibromyalgia patients and controls. A voxel-by-voxel group analysis was performed using Statistic Parametric Mapping 5 (SPM5). After treatment with gabapentin, 16 patients were considered "responders," with decrease in pain of greater than 50% as evaluated by visual analogue scale (VAS). The remaining 13 patients were considered "poor responders." RESULTS: We observed rCBF abnormalities, compared to control subjects, in fibromyalgia including hypoperfusion in the left culmen and hyperperfusion in the right precentral gyrus, right posterior cingulate, right superior occipital gyrus, right cuneus, left inferior parietal lobule, right middle temporal gyrus, left postcentral gyrus, and left superior parietal lobule. Compared to responders, poor responders exhibited hyperperfusion in the right middle temporal gyrus, left middle frontal gyrus, left superior frontal gyrus, right postcentral gyrus, right precuneus, right cingulate, left middle occipital gyrus, and left declive. The right middle temporal gyrus, left superior frontal gyrus, right precuneus, left middle occipital gyrus, and left declive exhibited high positive likelihood ratios. CONCLUSIONS: The present study revealed brain regions with significant hyperperfusion associated with the default-mode network, in addition to abnormalities in the sensory dimension of pain processing and affective-attentional areas in fibromyalgia patients. Furthermore, hyperperfusion in these areas was strongly predictive of poor response to gabapentin.

Arthritis Res Ther. 2010; 12(2):R64. Epub 2010 Apr 7

The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial

BACKGROUND: Sleep disorders affect many patients with chronic pain conditions. Cannabis has been reported by several patient populations to help sleep. We evaluated the safety and efficacy of nabilone, a synthetic cannabinoid, on sleep disturbance in fibromyalgia (FM), a disease characterized by widespread chronic pain and insomnia. METHODS: We conducted a randomized, double-blind, active-control, equivalency crossover trial to compare nabilone (0.5–1.0 mg before bedtime) to amitriptyline (10–20 mg before bedtime) in patients with FM with chronic insomnia. Subjects received each drug for 2 wk with a 2-wk washout period. The primary outcome was sleep quality, measured by the Insomnia Severity Index and the Leeds Sleep Evaluation Questionnaire. Secondary outcomes included pain, mood, quality of life, and adverse events (AEs). RESULTS: Thirty-one subjects were enrolled and 29 completed the trial (26 women, mean age 49.5 yr). Although sleep was improved by both amitriptyline and nabilone, nabilone was superior to amitriptyline (Insomnia Severity Index difference = 3.2; 95% confidence interval = 1.2–5.3). Nabilone was marginally better on the restfulness (Leeds Sleep Evaluation Questionnaire difference = 0.5 [0.0–1.0]) but not on wakefulness (difference = 0.3 [-0.2 to 0.8]). No effects on pain, mood, or quality of life were observed. AEs were mostly mild to moderate and were more frequent with nabilone. The most common AEs for nabilone were dizziness, nausea, and dry mouth. CONCLUSIONS: Nabilone is effective in improving sleep in patients with FM and is well tolerated. Low-dose nabilone given once daily at bedtime may be considered as an alternative to amitriptyline. Longer trials are needed to determine the duration of effect and to characterize long-term safety.

Anesth Analg. 2010 Feb; 110(2):604–10. Epub 2009 Dec 10

The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity

OBJECTIVE: To develop simple, practical criteria for clinical diagnosis of fibromyalgia that are suitable for use in primary and specialty care and that do not require a tender point examination, and to provide a severity scale for characteristic fibromyalgia symptoms. METHODS: We performed a multicenter study of 829 previously diagnosed fibromyalgia patients and controls using physician physical and interview examinations, including a widespread pain index (WPI), a measure of the number of painful body regions. Random forest and recursive partitioning analyses were used to guide the development of a case definition of fibromyalgia, to develop criteria, and to construct a symptom severity (SS) scale. RESULTS: Approximately 25% of fibromyalgia patients did not satisfy the American College of Rheumatology (ACR) 1990 classification criteria at the time of the study. The most important diagnostic variables were WPI and categorical scales for cognitive symptoms, unrefreshed sleep, fatigue, and number of somatic symptoms. The categorical scales were summed to create an SS scale. We combined the SS scale and the WPI to recommend a new case definition of fibromyalgia: (WPI > or =7 AND SS > or =5) OR (WPI 3-6 AND SS > or =9). CONCLUSION: This simple clinical case definition of fibromyalgia correctly classifies 88.1% of cases classified by the ACR classification criteria, and does not require a physical or tender point examination. The SS scale enables assessment of fibromyalgia symptom severity in persons with current or previous fibromyalgia, and in those to whom the criteria have not been applied. It will be especially useful in the longitudinal evaluation of patients with marked symptom variability.

Arthritis Care Res (Hoboken). 2010 May; 62(5):600–10.  Comment in: Arthritis Care Res (Hoboken). 2010 May; 62(5):583–4.