Fibromyalgia: Michigan

Crofford LJ, Appleton BE. · University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI, 48109-0680, USA. · Curr Rheumatol Rep. · Pubmed #11286671 No free full text.

Abstract: Fibromyalgia (FM) is a syndrome of chronic widespread musculoskeletal pain that is accompanied by sleep disturbance and fatigue. Clinical treatment usually includes lifestyle modifications and pharmacologic interventions meant to relieve pain, improve sleep quality, and treat mood disorders. These therapies are often ineffective or have been shown in clinical studies to have only short-term effectiveness. Pharmacologic treatments have considerable side effects. Patients may have difficulty complying with exercise-based treatments. Thus, patients seek alternative therapeutic approaches and physicians are routinely asked for advice about these treatments. This article reviews nontraditional treatment alternatives, from use of nutritional and herbal supplements to acupuncture and mind-body therapy. Little is known about efficacy and tolerance of complementary and alternative therapies in FM and other chronic musculoskeletal pain syndromes. Most studies on these treatments have been performed for osteoarthritis, rheumatoid arthritis, or focal musculoskeletal conditions. Clinical trials are scarce; the quality of these trials is often criticized because of small study population size, lack of appropriate control interventions, poor compliance, or short duration of follow-up. However, because of widespread and growing use of alternative medicine, especially by persons with chronic illnesses, it is essential to review efficacy and adverse effects of complementary and alternative therapies.

Glass JM, Park DC. · Institute for Social Research, The University of Michigan, 426 Thompson Street, Ann Arbor, MI 48106, USA. · Curr Rheumatol Rep. · Pubmed #11286668 No free full text.

Abstract: Fibromyalgia is a puzzling syndrome of widespread musculoskeletal pain. In addition to pain, patients with fibromyalgia frequently report that cognitive function, memory, and mental alertness have declined. A small body of literature suggests that there is cognitive dysfunction in fibromyalgia. This article addresses several questions that physicians may have regarding cognitive function in their patients. These questions concern the types of cognitive tasks that are problematic for patients with fibromyalgia, the role of psychological factors such as depression and anxiety, the role of physical factors such as pain and fatigue, the nature of patients' perceptions of their cognitive abilities, and whether patients can be tested for cognitive dysfunction. Critical areas for further investigation are highlighted.

Korszun A. · Department of Psychological Medicine, University of Wales College of Medicine, Heath Park Cardiff CF4 4XN, UK. · Curr Rheumatol Rep. · Pubmed #11123049 No free full text.

Abstract: Fibromyalgia (FM) is a syndrome of generalized muscle pain that is also associated with equally distressing symptoms of sleep disturbance and fatigue. FM shows clinical overlap with other stress-associated disorders, including chronic fatigue syndrome (CFS) and depression. All of these conditions have the features of disrupted sleep patterns and dysregulated biologic circadian rhythms, such as stress hormone secretion. This review focuses on the role of sleep and circadian rhythm disorders in FM and, in the absence of any specific treatment for FM, presents a pragmatic therapeutic approach aimed at identifying and treating comorbid sleep and depressive disorders, optimizing sleep habits, and judicious use of pharmacologic agents.

Crofford LJ, Appleton BE. · Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI 48109, USA. · Curr Rheumatol Rep. · Pubmed #11123045 No free full text.

This publication has no abstract.

Stohler CS. · Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor 48109-1078, USA. · J Orofac Pain. · Pubmed #10823041 No free full text.

This publication has no abstract.

Harris RE, Williams DA, McLean SA, Sen A, Hufford M, Gendreau RM, Gracely RH, Clauw DJ. · Chronic Pain and Fatigue Research Center, University of Michigan Medical Center, 24 Frank Lloyd Wright Drive, PO Box 385, Ann Arbor, MI 48106, USA. · Arthritis Rheum. · Pubmed #16258905 links to  free full text

Abstract: OBJECTIVE: A growing body of evidence suggests that real-time electronic assessments of pain are preferable to traditional paper-and-pencil measures. We used electronic assessment data derived from a study of patients with fibromyalgia (FM) to examine variability of pain over time and to investigate the implications of pain fluctuation in the context of a clinical trial. METHODS: The study group comprised 125 patients with FM who were enrolled in a randomized, placebo-controlled trial of milnacipran. Pain intensity levels were captured in real time by participants using electronic diaries. Variability in pain was assessed as the standard deviation of pain entries over time (pain variability index [PVI]). RESULTS: Substantial between-subject differences in pain variability were observed (mean +/- SD PVI 1.61 +/- 0.656 [range 0.27-4.05]). The fluctuation in pain report was constant over time within individuals (r = 0.664, P < 0.001). Individuals with greater variability were more likely to be classified as responders in a drug trial (odds ratio 6.14, P = 0.006); however, this association was primarily attributable to a greater change in pain scores in individuals receiving placebo (r = 0.460, P = 0.02) rather than active drug (r = 0.09, P > 0.10). CONCLUSION: Among individuals with FM, there were large between-subject differences in real-time pain reports. Pain variability was relatively constant over time within individuals. Perhaps the most important finding is that individuals with larger pain fluctuations were more likely to respond to placebo. It is not clear whether these findings are applicable only to patients with FM or whether they may also be seen in patients with other chronic pain conditions.

Crofford LJ, Rowbotham MC, Mease PJ, Russell IJ, Dworkin RH, Corbin AE, Young JP, LaMoreaux LK, Martin SA, Sharma U, Anonymous00343. · University of Michigan, Ann Arbor, USA. · Arthritis Rheum. · Pubmed #15818684 links to  free full text

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 alpha(2)-delta 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.

Glass JM, Lyden AK, Petzke F, Stein P, Whalen G, Ambrose K, Chrousos G, Clauw DJ. · Department of Psychiatry and Institute for Social Research, University of Michigan, Ann Arbor, MI, USA. · J Psychosom Res. · Pubmed #15518675 No free full text.

Abstract: OBJECTIVE: Abnormalities of the biological stress response (hypothalamic-pituitary-adrenal axis and the autonomic nervous system) have been identified in both fibromyalgia (FM) and chronic fatigue syndrome (CFS). Although these changes have been considered to be partly responsible for symptom expression, we examine an alternative hypothesis that these HPA and autonomic changes can be found in subsets of healthy individuals in the general population who may be at risk of developing these conditions. Exposure to "stressors" (e.g., infections, trauma, etc.) may lead to symptom expression (pain, fatigue, and other somatic symptoms) in part by precipitating lifestyle changes. In particular, we focus on the effect of deprivation of routine aerobic exercise on the development of somatic symptoms. METHODS: Eighteen regularly exercising (>/=4 h/week) asymptomatic, healthy adults refrained from physical activity for 1 week. We predicted that a subset of these individuals would develop symptoms of FM/CFS with exercise deprivation, and this manuscript focuses on the baseline HPA axis, immune, and autonomic function measures that may predict the development of symptoms. RESULTS: Eight of the subjects reported a 10% increase in one or more symptoms (pain, fatigue, mood) after 1 week of exercise deprivation. These symptomatic subjects had lower HPA axis (baseline cortisol prior to VO2max testing), immune (NK cell responsiveness to venipuncture), and autonomic function (measured by heart rate variability) at baseline (prior to cessation of exercise) when compared to the subjects who did not develop symptoms. CONCLUSIONS: A subset of subjects developed symptoms of pain, fatigue, or mood changes after exercise deprivation. This cohort was different from the individuals who did not develop symptoms in baseline measures of HPA axis, immune, and autonomic function. We speculate that a subset of healthy individuals who have hypoactive function of the biological stress response systems unknowingly exercise regularly to augment the function of these systems and thus suppress symptoms. These individuals may be at risk for developing chronic multisymptom illnesses (CMIs) (e.g., FM or CFS among others) when a "stressor" leads to lifestyle changes that disrupt regular exercise.

Crofford LJ, Young EA, Engleberg NC, Korszun A, Brucksch CB, McClure LA, Brown MB, Demitrack MA. · Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA. · Brain Behav Immun. · Pubmed #15157948 No free full text.

Abstract: The objective of this study was to evaluate and compare the basal circadian and pulsatile architecture of the HPA axis in groups of patients with FMS, CFS, or both syndromes with individually matched control groups. Forty patients with either FMS (n = 13), FMS and CFS (n = 12), or CFS (n = 15) were matched by age (18-65), sex, and menstrual status to healthy controls. Subjects were excluded if they met criteria for major Axis I psychiatric disorders by structured clinical interview (SCID). Subjects were admitted to the General Clinical Research Center where meals and activities were standardized. Blood was collected from an intravenous line every 10 min over 24 h for analysis of ACTH and cortisol. Samples were evaluable for ACTH in 36 subject pairs and for cortisol in 37 subject pairs. There was a significant delay in the rate of decline from acrophase to nadir for cortisol levels in patients with FMS (P <.01). Elevation of cortisol in the late evening quiescent period was evident in half of the FMS patients compared with their control group, while cortisol levels were numerically, but not significantly, lower in the overnight period in patients with CFS compared with their control group. Pulsatility analyses did not reveal statistically significant differences between patient and control groups. We conclude that the pattern of differences for basal circadian architecture of HPA axis hormones differs between patients with FMS and CFS compared to their matched control groups. The abnormalities in FMS patients are consistent with loss of HPA axis resiliency.

Hsu MC, Harris RE, Sundgren PC, Welsh RC, Fernandes CR, Clauw DJ, Williams DA. · Department of Physical Medicine & Rehabilitation, University of Michigan Chronic Pain & Fatigue Research Center, 24 Frank Lloyd Wright Drive, Lobby M, PO Box 385, Ann Arbor, MI 48106, USA. · Pain. · Pubmed #19375224 No free full text.

Abstract: Fibromyalgia (FM) is thought to involve abnormalities in central pain processing. Recent studies involving small samples have suggested alterations in gray matter volume (GMV) in brains of FM patients. Our objective was to verify these findings in a somewhat larger sample using voxel-based morphometry (VBM), while controlling for the presence of affective disorders (AD). T1-weighted magnetic resonance image (MRI) brain scans were obtained on 29 FM patients with AD, 29 FM patients without AD, and 29 age-matched healthy controls (HCs) using a 3T scanner. Segmentation, spatial normalization, and volumetric modulation were performed using an automated protocol within SPM5. Smoothed gray matter segments were entered into a voxel-wise one-way ANOVA, and a search for significant clusters was performed using thresholding methods published in previous studies (whole-brain threshold of p<.05 correcting for multiple comparisons; region-of-interest (ROI) threshold of p< or =.001 uncorrected, or p<.05 small-volume corrected). The whole-brain analysis did not reveal any significant clusters. ROI-based analysis revealed a significant difference in left anterior insula GMV among the three groups (xyz={-28, 21, 9}; p=.026, corrected). However, on post-hoc testing, FM patients without AD did not differ significantly from HC with respect to mean GMV extracted from this cluster. A significant negative correlation was found between mean cluster GMV and scores of trait anxiety (State-Trait Personality Inventory, Trait Anxiety scale; rho=-.470, p<.001). No other significant clusters were found on ROI-based analysis. Our results emphasize the importance of correcting for AD when carrying out VBM studies in chronic pain.

Harris RE, Clauw DJ. · Department of Anesthesiology, The University of Michigan, Ann, Arbor, MI, USA. · Ther Clin Risk Manag. · Pubmed #19337439 links to  free full text

Abstract: Fibromyalgia syndrome is a common chronic pain disorder of unknown etiology. The lack of understanding of the pathophysiology of fibromyalgia has made this condition frustrating for patients and clinicians alike. The most common symptoms of this disorder are chronic widespread pain, fatigue, sleep disturbances, difficulty with memory, and morning stiffness. Emerging evidence points towards augmented pain processing within the central nervous system (CNS) as having a primary role in the pathophysiology of this disorder. Currently the two drugs that are approved by the United States Food and Drug Administration (FDA) for the management of fibromyalgia are pregabalin and duloxetine. Newer data suggests that milnacipran, a dual norepinephrine and serotonin reuptake inhibitor, may be promising for the treatment of fibromyalgia. A double-blind, placebo-controlled trial of milnacipran in 125 fibromyalgia patients showed significant improvements relative to placebo. Milnacipran given either once or twice daily at doses up to 200 mg/day was generally well tolerated and yielded significant improvements relative to placebo on measures of pain, patient's global impression of change in their disease state, physical function, and fatigue. Future studies are needed to validate the efficacy of milnacipran in fibromyalgia.

Klyman CM, Browne M, Austad C, Spindler EJ, Spindler AC. · Wayne State University School of Medicine, Bloomfield Hills, MI 48302-1408, USA. · J Am Acad Psychoanal Dyn Psychiatry. · Pubmed #19113960 No free full text.

Abstract: Some patients are unable to participate in a good, mutually cooperative relationship with their primary care doctors. They may have long-standing psychosocial difficulties exacerbated by chronic, painful, or life-threatening illnesses. Some may have somatic symptoms that they define as evidence only of an identified illness but which are reflections of psychic misery with roots in their thoughts, feelings, and relationships. This article describes a Workshop approach to teaching those patients' physicians how to make diagnostic use of their own "gut reactions" to understand the common dynamics of the doctor- patient relationship; to understand the psychological aspects of various physical symptoms; and manage challenging patients to optimize their quality of life, cost-effectiveness of treatment and minimize physician "burnout."

Clauw DJ, Mease P, Palmer RH, Gendreau RM, Wang Y. · Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan Medical School, Ann Arbor, Michigan 48106, USA. · Clin Ther. · Pubmed #19108787 No free full text.

Abstract: BACKGROUND: Preclinical and clinical studies have suggested that milnacipran, a dual norepinephrine-serotonin reuptake inhibitor, may be efficacious in the treatment of fibromyalgia (FM). OBJECTIVE: This study was conducted to evaluate the efficacy and tolerability of milnacipran in treating the multiple domains of FM. METHODS: This was a multicenter, double-blind, placebo-controlled trial. Adult patients (age 18-70 years) who met 1990 American College of Rheumatology criteria for FM were randomized to receive milnacipran 100 mg/d, milnacipran 200 mg/d, or placebo for 15 weeks. Because this was a pivotal registration trial, the primary end points were chosen to investigate efficacy for 2 potential indications: the treatment of FM and the treatment of FM pain. Thus, the 2 primary efficacy end points were rates of FM composite responders and FM pain composite responders. FM composite responders were defined as patients concurrently experiencing clinically meaningful improvements in the following 3 domain criteria: pain (> or = 30% improvement, as recorded in an electronic diary); patients' global status (a rating of very much improved or much improved on the Patient Global Impression of Change [PGIC] scale); and physical function (a > or = 6-point improvement on the 36-item Short-Form Health Survey [SF-36] Physical Component Summary score). FM pain composite responders were defined as those who met the pain and PGIC criteria. Adverse events reported by patients or observed by investigators were recorded throughout the trial. RESULTS: Of 2270 patients screened, 1196 were randomized to receive milnacipran 100 mg/d (n = 399), milnacipran 200 mg/d (n = 396), or placebo (n = 401). The majority of patients were female (96.2%) and white (93.5%). The population had a mean age of 50.2 years, a mean baseline weight of 180.8 pounds, and a mean baseline body mass index of 30.6 kg/m(2). Compared with placebo, significantly greater proportions of milnacipran-treated patients were FM composite responders (100 mg/d: P = 0.01; 200 mg/d: P = 0.02) and FM pain composite responders (100 mg/d: P = 0.03; 200 mg/d: P = 0.004). Milnacipran was associated with significant improvements in pain after 1 week of treatment (100 mg/d: P = 0.004; 200 mg/d: P = 0.04), as well as significant improvements in multiple secondary efficacy end points, including global status (PGIC: P<0.001 for both doses), physical function (SF-36 physical functioning domain-100 mg/d: P < 0.001; 200 mg/d: P = 0.02), and fatigue (Multidimensional Fatigue Inventory- 100 mg/d: P = 0.04). The most commonly reported adverse events with milnacipran were nausea (100 mg/d, 34.3%; 200 mg/d, 37.6%), headache (18.0% and 17.7%, respectively), and constipation (14.3% and 17.9%). Adverse events resulted in premature study discontinuation in 19.5% and 23.7% of those who received milnacipran 100 and 200 mg/d, respectively, compared with 9.5% of placebo recipients. CONCLUSION: In these adult patients with FM, both doses of milnacipran (100 and 200 mg/d) were associated with significant improvements in pain and other symptoms. Clinical Trials Identification Number: NCT00098124.

Zhang Y, Holliman C, Tang D, Fast D, Michael S. · Pharmacokinetics, Dynamics & Metabolism, Pfizer Global Research and Development, Pfizer Inc., Ann Arbor, MI 48105, USA. · J Chromatogr B Analyt Technol Biomed Life Sci. · Pubmed #18755638 No free full text.

Abstract: Pregabalin (Lyrica) is the first compound approved to treat the neural pain associated with fibromyalgia. Pregabalin is the S-enantiomer of a gamma-amino acid analogue and chiral separation from its R-enantiomer must be achieved to support metabolic studies. The direct chiral separation of pregabalin from its R-enantiomer has been developed and HPLC/MS/MS assays have been validated to support isolated perfused rat kidney studies. The separation was developed through serial coupling of various macrocyclic glycopeptide stationary phases until partial separation of the enantiomers was achieved. Identification of the resolving stationary phase followed by optimization of the mobile phase enabled the baseline resolution of the enantiomers using mass spectrometry compatible solvents and modifiers. Assays were developed and validated for quantitation of the enantiomers from rat urine, isolated rat kidney perfusate, and isolated rat kidney perfusate ultrafiltrate to support pregabalin metabolic studies.

Geisser ME, Strader Donnell C, Petzke F, Gracely RH, Clauw DJ, Williams DA. · Chronic Pain and Fatigue Research Center, Dept. of Internal Medicine, Div. of Rheumatology, Univ. of Michigan, Ann Arbor, MI 48108, USA. · Psychosomatics. · Pubmed #18448779 links to  free full text

Abstract: BACKGROUND: Somatic symptoms are common in conditions such as fibromyalgia (FM) and chronic fatigue syndrome (CFS). OBJECTIVE: Authors investigated a potential shared pathologic mechanism: a generalized perceptual abnormality where there is heightened responsiveness to varied sensory stimulation, including pain. METHOD: A composite measure of sensory sensitivity was created and compared with measures of somatic symptoms, comorbid psychological disturbances, and self-reported physical functioning in 38 patients with FM and/or CFS. RESULTS: Sensory amplification influenced physical functioning indirectly through pain intensity, and physical symptoms and fatigue also independently contributed to physical functioning. CONCLUSION: Sensory amplification may be an underlying pathophysiologic mechanism in these disorders that is relatively independent of depression and depressive symptoms.

Clemens JQ, Meenan RT, O'Keeffe Rosetti MC, Kimes TA, Calhoun EA. · Department of Urology, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA. · J Urol. · Pubmed #18423759 No free full text.

Abstract: PURPOSE: We used physician assigned diagnoses in an electronic medical record to assess comorbidities associated with interstitial cystitis. MATERIALS AND METHODS: A computer search of the administrative database at Kaiser Permanente Northwest, Portland, Oregon was performed for May 1, 1998 to April 30, 2003. All women with a medical record diagnosis of interstitial cystitis (ICD-9 code 595.1) were identified. These cases were then matched with 3 controls each based on age and duration in the health plan. The medical diagnoses (using ICD-9 codes restricted to 3 digits) assigned to these 2 groups were compared using the OR. RESULTS: A total of 239 cases and 717 matched controls were analyzed. There were 23 diagnoses that were significantly more common in cases than in controls (p < or = 0.005). Seven of these 23 diagnoses were other urological or gynecological codes used to describe pelvic symptoms. Additional specific conditions associated with interstitial cystitis were gastritis (OR 12.2), child abuse (OR 9.3), fibromyalgia (OR 3.0), anxiety disorder (OR 2.8), headache (OR 2.5), esophageal reflux (OR 2.2), unspecified back disorder (OR 2.2) and depression (OR 2.0). CONCLUSIONS: A diagnosis of interstitial cystitis was associated with multiple other unexplained physical symptoms and certain psychiatric conditions. Studies to explore the possible biological explanations for these associations are needed. Interstitial cystitis was also associated with a history of child abuse, although 96% of patients with IC did not have this diagnosis.

Saber AA, Boros MJ, Mancl T, Elgamal MH, Song S, Wisadrattanapong T. · Department of Surgery, Michigan State University/Kalamazoo Center for Medical Studies, 1000 Oakland Drive, Kalamazoo, MI 49008, USA. · Obes Surg. · Pubmed #18401670 No free full text.

Abstract: BACKGROUND: Fibromyalgia is a chronic debilitating disorder affecting 3-5% of the US population. Treatment of this disorder is a challenge. The incidental finding of improvement of fibromyalgia following laparoscopic Roux-en-Y gastric bypass stimulated us to study this phenomenon. METHODS: A retrospective chart review of patients with fibromyalgia who underwent laparoscopic Roux-en-Y gastric bypass. RESULTS: Postoperative decrease in median of BMI from 49.4 to 29.7 was significant (p value = 0.0010). This was associated with statistically significant improvement in median of pain score (p value = 0.0010) and median points of tenderness (p value = 0.0010). CONCLUSION: Significant weight loss following laparoscopic Roux-en-Y gastric bypass is associated with resolution or improvement of fibromyalgia. Consequently, the bariatric surgeon should be a member of the multidisciplinary team approach for treating fibromyalgia.

Petrou M, Harris RE, Foerster BR, McLean SA, Sen A, Clauw DJ, Sundgren PC. · Department of Radiology, Division of Neuroradiology, University of Michigan Hospitals, 1500 E. Medical Center Dr, Ann Arbor, MI 48109-0030, USA. · AJNR Am J Neuroradiol. · Pubmed #18339723 links to  free full text

Abstract: BACKGROUND AND PURPOSE: Widespread pain sensitivity in patients with fibromyalgia (FM) suggests a central nervous system (CNS)-processing problem. Therefore, it is conceivable that metabolic alterations exist in pain-processing brain regions of people with FM compared with healthy controls (HC) and that such metabolic data could correlate with clinical symptoms. The purpose of this study was to test these hypotheses using proton MR spectroscopy ((1)H-MR spectroscopy). MATERIALS AND METHODS: There were 21 patients with FM and 27 HC who underwent conventional structural MR imaging and additional 2D-chemical shift imaging (CSI) MR-spectroscopy sequences. For the 2D-CSI spectroscopy, larger volumes of interest (VOIs) were centered at the level of the basal ganglia and the supraventricular white matter. Within these larger areas, 16 smaller voxels were placed in a number of regions previously implicated in pain processing. N-acetylaspartate (NAA)/creatine(Cr), choline (Cho)/Cr and NAA/Cho ratios were calculated for each voxel. Subjects underwent clinical and experimental pain assessment. RESULTS: Mean metabolite ratios and ratio variability for each region were analyzed by using repeated-measures analysis of variance (ANOVA). Correlations between clinical symptoms and metabolite ratios were assessed. Cho/Cr variability in the right dorsolateral prefrontal cortex (DLPFC) was significantly different in the 2 groups; a significant correlation between Cho/Cr in this location and clinical pain was present in the FM group. Evoked pain threshold correlated significantly with NAA/Cho ratios in the left insula and left basal ganglia. CONCLUSION: Our data suggest that there are baseline differences in the variability of brain metabolite relative concentrations between patients with FM and HC, especially in the right DLPFC. Furthermore, there are significant correlations between metabolite ratios and clinical and experimental pain parameters in patients with FM.

Burns JW, Crofford LJ, Chervin RD. · Michigan Tech Research Institute, Michigan Technological University, 3600 Green Court, Suite 100, Ann Arbor, MI 48105, USA. · Sleep Med. · Pubmed #18314389 No free full text.

Abstract: OBJECTIVE: To determine whether previously described sleep stage dynamics, reflecting the mean duration of specific sleep stages, may have clinical utility in a sample of patients with fibromyalgia syndrome (FMS) and controls. METHODS: Women with FMS (n=15, screened to exclude other sleep disorders) and age-matched women in good health (n=15) were studied with nocturnal polysomnography, multiple sleep latency tests, 2-week pain diaries, and a measure of current pain intensity. RESULTS: The FMS subjects, in comparison to controls, did not show differences in several common polysomnographic measures, except for increased numbers of stage shifts (126+/-27 vs. 107+/-22, p=.042). Mean durations for episodes of total sleep, stage 1 sleep, stage 3/4 sleep, and rapid eye movement sleep failed to distinguish FMS and control subjects (Wilcoxon rank sum tests, p>.10 for each), but those for stage 2 sleep were shorter in the FMS subjects (p=.006), possibly because transitions to stage 3/4 sleep occurred more quickly (p=.036). Shorter stage 2 sleep durations predicted higher pain diary scores (Spearman rho=-.56, p=.0014) and current pain intensity (rho=-.71, p<0.0001). CONCLUSIONS: Sleep stage dynamic, and, more specifically, shorter durations of sleep stage 2 periods, distinguish FMS and control female subjects and may predict pain levels experienced in FMS. Analysis of the lengths of individual sleep stages, in addition to the usual sleep stage amounts and percentages listed in standard polysomnogram reports, may have clinical utility.

Harris RE, Sundgren PC, Pang Y, Hsu M, Petrou M, Kim SH, McLean SA, Gracely RH, Clauw DJ. · University of Michigan, Chronic Pain and Fatigue Research Center, Ann Arbor, MI 48106, USA. · Arthritis Rheum. · Pubmed #18311814 links to  free full text

Abstract: OBJECTIVE: Fibromyalgia (FM) is a chronic widespread pain condition that is thought to arise from augmentation of central neural activity. Glutamate (Glu) is an excitatory neurotransmitter that functions in pain-processing pathways. This study was carried out to investigate the relationship between changing levels of Glu within the insula and changes in multiple pain domains in patients with FM. METHODS: Ten patients with FM underwent 2 sessions of proton magnetic resonance spectroscopy (H-MRS) and 2 sessions of functional magnetic resonance imaging (FMRI), each conducted before and after a nonpharmacologic intervention to reduce pain. During H-MRS, the anterior and posterior insular regions were examined separately using single-voxel spectroscopy. The levels of Glu and other metabolites were estimated relative to levels of creatine (Cr) (e.g., the Glu/Cr ratio). During FMRI, painful pressures were applied to the thumbnail to elicit neuronal activation. Experimental pressure-evoked pain thresholds and clinical pain ratings (on the Short Form of the McGill Pain Questionnaire [SF-MPQ]) were also assessed prior to each imaging session RESULTS: Both experimental pain (P = 0.047 versus pretreatment) and SF-MPQ-rated clinical pain (P = 0.043 versus pretreatment) were reduced following treatment. Changes from pre- to posttreatment in Glu/Cr were negatively correlated with changes in experimental pain thresholds (r = -0.95, P < 0.001) and positively correlated with changes in clinical pain (r = 0.85, P = 0.002). Changes in the FMRI-determined blood oxygenation level-dependent effect (a measure of neural activation) were positively correlated with changes in Glu/Cr within the contralateral insula (r = 0.81, P = 0.002). CONCLUSION: Changes in Glu levels within the insula are associated with changes in multiple pain domains in patients with FM. Thus, H-MRS data may serve as a useful biomarker and surrogate end point for clinical trials of FM.

Geisser ME, Glass JM, Rajcevska LD, Clauw DJ, Williams DA, Kileny PR, Gracely RH. · Chronic Pain and Fatigue Research Center, Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, Michigan 48108, USA. · J Pain. · Pubmed #18280211 No free full text.

Abstract: Fibromyalgia (FM) is characterized by widespread tenderness. Studies have also reported that persons with FM are sensitive to other stimuli, such as auditory tones. We hypothesized that subjects with FM would display greater sensitivity to both pressure and auditory tones and report greater sensitivity to sounds encountered in daily activities. FM subjects (n = 30) and healthy control subjects (n = 28) were administered auditory tones and pressure using the same psychophysical methods to deliver the stimuli and a common way of scaling responses. Subjects were also administered a self-report questionnaire regarding sensitivity to everyday sounds. Participants with FM displayed significantly greater sensitivity to all levels of auditory stimulation (Ps < .05). The magnitude of difference between FM patients' lowered auditory sensitivity (relative to control subjects) was similar to that seen with pressure, and pressure and auditory ratings were significantly correlated in both control subjects and subjects with FM. FM patients also were more sensitive to everyday sounds (t = 8.65, P < .001). These findings support that FM is associated with a global central nervous system augmentation in sensory processing. Further research is needed to examine the neural substrates associated with this abnormality and its role in the etiology and maintenance of FM. PERSPECTIVE: Muscle tenderness is the hallmark of FM, but the findings of this study and others suggest that persons with FM display sensitivity to a number of sensory stimuli. These findings suggest that FM is associated with a global central nervous system augmentation of sensory information. These findings may also help to explain why persons with FM display a number of comorbid physical symptoms other than pain.

Harris RE, Clauw DJ, Scott DJ, McLean SA, Gracely RH, Zubieta JK. · Department of Internal Medicine, The University of Michigan, Ann Arbor, Michigan 48109, USA. · J Neurosci. · Pubmed #17855614 links to  free full text

Abstract: The underlying neurophysiology of acute pain is fairly well characterized, whereas the central mechanisms operative in chronic pain states are less well understood. Fibromyalgia (FM), a common chronic pain condition characterized by widespread pain, is thought to originate largely from altered central neurotransmission. We compare a sample of 17 FM patients and 17 age- and sex-matched healthy controls, using mu-opioid receptor (MOR) positron emission tomography. We demonstrate that FM patients display reduced MOR binding potential (BP) within several regions known to play a role in pain modulation, including the nucleus accumbens, the amygdala, and the dorsal cingulate. MOR BP in the accumbens of FM patients was negatively correlated with affective pain ratings. Moreover, MOR BP throughout the cingulate and the striatum was also negatively correlated with the relative amount of affective pain (McGill, affective score/sensory score) within these patients. These findings indicate altered endogenous opioid analgesic activity in FM and suggest a possible reason for why exogenous opiates appear to have reduced efficacy in this population.

Sundgren PC, Petrou M, Harris RE, Fan X, Foerster B, Mehrotra N, Sen A, Clauw DJ, Welsh RC. · Department of Radiology, University of Michigan, 1500 E Medical Center Drive, Ann Arbor, MI 48109-0030, USA. · Acad Radiol. · Pubmed #17574134 No free full text.

This publication has no abstract.

Young JL, Redmond JC. · Rochester Center for Behavioral Medicine, Rochester Hills, MI. · Psychopharmacol Bull. · Pubmed #17285103 No free full text.

Abstract: Adult attention deficit hyperactivity disorder (ADHD) may share common features with fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS). In an outpatient psychiatric clinic, a number of adult patients who presented primarily with symptoms of ADHD, predominately inattentive type, also reported unexplained fatigue, widespread musculoskeletal pain or a pre-existing diagnosis of CFS or FMS. As expected, ADHD pharmacotherapy usually attenuated the core ADHD symptoms of inattention, distractibility, hyperactivity, and impulsivity. Less expected was the observation that some patients also reported amelioration of pain and fatigue symptoms. The utility of ADHD medications in FMS and CFS states may be their innate arousal and enhanced filtering properties. This model supposes that FMS and CFS are central processing problems rather than peripheral disorders of muscles and joints.

Gillis ME, Lumley MA, Mosley-Williams A, Leisen JC, Roehrs T. · Department of Psychoogy, Wayne State University, Detroit, MI 48202, USA. · Ann Behav Med. · Pubmed #16972811 No free full text.

Abstract: BACKGROUND: The presence and severity of the chronic pain syndrome fibromyalgia (FM) is associated with unresolved stress and emotional regulation difficulties. Written emotional disclosure is intended to reduce stress and may improve health of people with FM. PURPOSE: This study tests the effects of at-home, written emotional disclosure about stressful experiences on the health of people with FM and uses multiple follow-ups to track the time course of effects of disclosure. METHODS: Adults with FM (intention-to-treat, n=83; completers, n=72) were randomized to write for 4 days at home about either stressful experiences (disclosure group) or neutral time management (control group). Group differences in immediate mood effects and changes in health from baseline to 1-month and 3-month follow-ups were examined. RESULTS: Written disclosure led to an immediate increase in negative mood, which did not attenuate across the 4 writing days. Repeated-measures analyses from baseline to each follow-up point were conducted on both intention-to-treat and completer samples, which showed similar outcomes. At 1 month, disclosure led to few health benefits, but control writing led to less negative affect and more perceived support than did disclosure. At 3-month follow-up, these negative affect and social support effects disappeared, and written disclosure led to a greater reduction in global impact, poor sleep, health care utilization, and (marginally) physical disability than did control writing. Interpretation of these apparent benefits needs to be made cautiously, however, because the disclosure group had somewhat poorer health than controls at baseline and the control group showed some minor worsening over time. CONCLUSIONS: Written emotional disclosure can be conducted at home, and there is tentative evidence that disclosure benefits the health of people with FM. The benefits, however, may be delayed for several months after writing and may be of limited clinical significance.