Fibromyalgia notable studies

Fibromyalgia notable studies houses the research for the Fibromyalgia (FM/FMS) page.

Notable studies

2000-2004

• 2002, Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia

Reported as Fibromyalgia Pain Isn't All In Patient's Heads, New Brain Study Finds

• 2004, A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing

2005-2009

• 2006, Prevalence of fibromyalgia syndrome in migraine patients.

• 2007, Neuroimaging revolutionizes therapeutic approaches to chronic pain

Chronic pain is a multidimensional process that now must be considered as a chronic degenerative disease not only affecting sensory and emotional processing, but also producing an altered brain state. Therapeutic interventions should be reconsidered in this context.

Schematic Examples of CNS Structural Changes. Red circles signify decreased gray matter density relative to controls. A. Subjects with chronic back pain show decreases in gray matter density in bilateral dorsolateral prefrontal cortex (DLPFC) and right anterior thalamus (adapted from [25]). B. Patients with fibromyalgia show decreases in cingulate cortex (CC), medial prefrontal cortex (Med. PFC), parahippocampal gyrus (PHG) and insula (adapted from [27]). 3-D surface renderings were created using Freesurfer. Borsook et al. Molecular Pain 2007 3:25 doi:10.1186/1744-8069-3-25

• 2007, Clinical and Economic Characteristics of Patients With Fibromyalgia Syndrome (Abstract)

• 2008, Symptom Clusters in Fibromyalgia (Abstract)

• 2009, Fibromyalgia comorbidity in primary headaches.

2010-2014

• 2010, Interstitial cystitis/painful bladder syndrome and associated medical conditions with an emphasis on irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome.

• 2010, Pain Inhibition Is Deficient in Chronic Widespread Pain but Normal in Major Depressive Disorder

• 2011, Improving the Recognition and Diagnosis of Fibromyalgia

• 2011, Fibromyalgia and neuropathic pain - differences and similarities. A comparison of 3057 patients with diabetic painful neuropathy and fibromyalgia.

• 2011, The Clinical Concept of Fibromyalgia as a Changing Paradigm in the Past 20 Years

• 2011, The comparative burden of mild, moderate and severe Fibromyalgia: results from a cross-sectional survey in the United States

• 2012, Fibromyalgia Syndrome: An Overview of Pathophysiology, Diagnosis and Management

Pathophysiology: Although the etiology remains unclear, characteristic alterations in the pattern of sleep and changes in neuroendocrine transmitters such as serotonin, substance P, growth hormone and cortisol suggest that regulation of the autonomic and neuro-endocrine system appears to be the basis of the syndrome. Fibromyalgia is not a life-threatening, deforming, or progressive disease. Anxiety and depression are the most common association. Aberrant pain processing, which can result in chronic pain, may be the result of several interplaying mechanisms. Central sensitization, blunting of inhibitory pain pathways and alterations in neurotransmitters lead to aberrant neuro-chemical processing of sensory signals in the CNS, thus lowering the threshold of pain and amplification of normal sensory signals causing constant pain.

The frequent co-morbidity of fibromyalgia with mood disorders suggests a major role for the stress response and for neuroendocrine abnormalities. The hypothalamic pituitary axis (HPA) is a critical component of the stress-adaptation response. In FMS, stress adaptation response is disturbed leading to stress induce symptoms. Psychiatric co-morbidity has been associated with FMS and needs to be identified during the consultation process, as this requires special consideration during treatment.

• 2012, Dysfunctional endogenous analgesia during exercise in patients with chronic pain: To exercise or not to exercise?
• 2014, Aquatic exercise training for fibromyalgia.

2015-2019

• 2015, Evidence for brain glial activation in chronic pain patients

Whole-brain voxel-wise analyses. (A) Median SUVR map from healthy controls (n = 9) and patients with chronic LBP (n = 10) are presented. Matched-pairs tests (nine versus nine) revealed significantly higher TSPO levels in patients, in thalamus, pre- and postcentral gyri, and paracentral lobule (P < 0.05 corrected for multiple comparisons; permutation testing, 10 000 permutations). As two patients were matching the same controls, the analyses were performed first using the patient best matching the control. A second analysis was performed using the other patient, limiting our search to significant clusters from the first analysis, with identical results. (B) Boxplots for each of the four regions demonstrating statistically higher SUVRs in patients are shown for illustrative purposes. postc. = postcentral; g. = gyrus; parac. lob. = postcentral lobule; prec. = precentral.

• 2015, Some oxidative and antioxidative parameters and their relationship with clinical symptoms in women with fibromyalgia syndrome

• 2015, Understanding the Association of Fatigue With Other Symptoms of Fibromyalgia: Development of a Cluster Model

• 2015, Evaluation of Antiviral Antibodies against Epstein-Barr Virus and Neurotransmitters in Patients with Fibromyalgia

• 2015, Sleep is associated with task-negative brain activity in fibromyalgia participants with comorbid chronic insomnia

• 2015, Cognitive performance is related to central sensitization in patients with chronic whiplash-associated disorders and fibromyalgia: a case-control study

• 2015, Fibromyalgia: A search for markers and their evaluation throughout a treatment

• 2015, Normalization of aberrant resting state functional connectivity in fibromyalgia patients following a three-month physical exercise therapy

• 2015, Thalamic Mechanisms Underlying Alpha-Delta Sleep with Implications for Fibromyalgia

Our model also suggests that drugs that specifically target the somatosensory thalamus may be effective in treating fibromyalgia.

• 2015, The Iceberg Nature of Fibromyalgia Burden: The Clinical and Economic Aspects

• 2015, The effects of aquatic, isometric strength-stretching and aerobic exercise on physical and psychological parameters of female patients with fibromyalgia syndrome

The probability densities of CCC test scores of 119 controls, 160 FM patients, 100 SLE patients and 98 RA patients

• 2015, Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis, and systemic lupus erythematosus: a potentially useful tool in differential diagnosis.

Nearly 500 FM, autoimmune and healthy control patients underwent testing for cytokine/chemokine activity after mitogenic stimulation. Using a numerical score, all three groups had unique patterns with FM patients demonstrating less response to stimulation. This cytokine profile test had a 93 % sensitivity and an 89.4 % specificity for the diagnosis of FM. We also found that these profiles are relatively sensitive and specific for FM compared to SLE and RA. It remains unclear if these differences are directly related to the pathogenesis of FM.

• 2015, The Somatosensory Link in Fibromyalgia: Functional Connectivity of the Primary Somatosensory Cortex Is Altered by Sustained Pain and Is Associated With Clinical/Autonomic Dysfunction
• 2015, Identification of a MicroRNA Signature for the Diagnosis of Fibromyalgia

• 2016, Fibromyalgia syndrome: metabolic and autophagic processes in intermittent cold stress mice.

• 2016, The association between borderline personality disorder, fibromyalgia and chronic fatigue syndrome: systematic review

There does not appear to be firm and consistent evidence to support the hypothesis that the prevalence of BPD (Borderline Personality Disorder) would be higher in individuals with fibromyalgia compared with the general population.

• 2016, Fibromyalgia Is Correlated with Retinal Nerve Fiber Layer Thinning

Fibromyalgia causes subclinical axonal damage in the RNFL that can be detected using innocuous and non-invasive OCT, even in the early disease stages. The impact on the RNFL in the temporal sectors is greater in patients with biologic fibromyalgia, suggesting the presence of neurodegenerative processes in this subgroup of patients with fibromyalgia.

Fig 1. Representation and interpretation of the report from the Axonal application of the Spectralis optical coherence tomography in a control (left side) and in a patient with fibromyalgia and retina nerve fiber layer thinning (right side)

• 2016, The prevalence of severe fatigue in rheumatic diseases: an international study.

• 2016, Characteristics of Disturbed Sleep in Patients With Fibromyalgia Compared With Insomnia or With Pain-Free Volunteers

• 2016, Is Efficacy of Milnacipran in Fibromyalgia Predictable? A Data Mining Analysis of Baseline and Outcome Variables.

• 2017, The degree of cardiac baroreflex involvement during active standing is associated with the quality of life in fibromyalgia patients. (Orthostatic intollerance.)

• 2017, Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma

Figure 2

• 2017, Towards a neurophysiological signature for fibromyalgia.

Here, we identify a set of three brain patterns based on fMRI responses to pressure pain and non-painful multisensory stimulation. These patterns, taken together, discriminate FM from matched healthy controls with 92% sensitivity and 94% specificity.

Figure 2. Multivariate brain pattern that predicts fibromyalgia status on the basis of brain activation during painful (pressure) stimulation. Positive weight values reflect higher pain-evoked activation in FM patients relative to healthy participants, whereas negative weight values reflect reduced pain-evoked activation in FM patients. A. SVM pattern of whole-brain voxel weights that optimizes classification of FM patients and healthy participants. We provide the voxel-by-voxel weights for three representative regions (anterior SII, right dorsolateral and dorsomedial PFC) to illustrate the concept of weighted pattern. B. Regions whose voxel weights contributed most reliably to the prediction of FM status (q<0.05 FDR-corrected for the first two rows; p-uncorrected<0.001 to further illustrate the findings).

• 2017, Diagnostic confounders of chronic widespread pain: not always fibromyalgia

• 2018, A Blinded, Randomized, Placebo-Controlled Study to Investigate the Efficacy and Safety of Ferric Carboxymaltose in Iron-Deficient Patients with Fibromyalgia.

• 2018, Primary and Secondary Fibromyalgia Are The Same: The Universality of Polysymptomatic Distress "PFM and SFM are equivalent regarding symptom burden."

• 2018, SNPs in inflammatory genes CCL11, CCL4 and MEFV in a fibromyalgia family study

SNPs with significant TDTs were found in 36% of the cohort for CCL11 and 12% for MEFV, along with a protein variant in CCL4 (41%) that affects CCR5 down-regulation, supporting an immune involvement for FM.

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  Fig 1. Expression of wild type and variant (Ala23Thr) CCL11

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  Fig 3. Functional analyses of WT vs varCCL4 in immature dendritic cells or CEM.NKR CCR5 T-cells

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  Fig 4. Wild type versus varCCL4 in the down-regulation of CCR5 in a 9 day mixed lymphocyte culture

• 2018, Cognitive Impairment in Fibromyalgia: A Meta-Analysis of Case-Control Studies

• 2018, A comparison of the clinical manifestation and pathophysiology of myofascial pain syndrome and fibromyalgia: implications for differential diagnosis and management

See Table 1 "Summary of the pathophysiology of fibromyalgia and myofascial pain syndrome." p. 29 (p. 4 of PDF)

• 2018, Brain glial activation in fibromyalgia – A multi-site positron emission tomography investigation

Our work provides the first in vivo evidence supporting a role for glial activation in FM pathophysiology. Given that the elevations in [¹¹C]PBR28 signal were not also accompanied by increased [¹¹C]-_L-deprenyl-D₂ signal, our data suggests that microglia, but not astrocytes, may be driving the TSPO elevation in these regions. Although [¹¹C]-_L-deprenyl-D₂ signal was not found to be increased in FM patients, larger studies are needed to further assess the role of possible astrocytic contributions in FM. Overall, our data support glial modulation as a potential therapeutic strategy for FM.

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  Fig 1. Fibromyalgia Glial Activation Voxelwise group differences in [¹¹C]PBR28 VT. A

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  Fig. 2. Fibromyalgia Glial Activation Voxelwise group differences in [¹¹C]PBR28 SUVR A

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  Fig. 3. Fibromyalgia Glial Activation Agreement between SUVR and VT analyses A

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  Fig 4. Fibromyalgia Glial Cells Associations between [¹¹C]PBR28 SUVR and clinical variables

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  Fig. 5. Fibromyalgia Glial Cells Absence of group differences in [¹¹C]-L-deprenyl-D2 λk3

• 2018, Altered Cervical Spinal Cord Resting State Activity in Fibromyalgia (See: "Supporting Information" for images.)
• 2018, Fibromyalgia diagnosis and biased assessment: Sex, prevalence and bias

What we did not find in our unbiased CritFM samples was 9:1 female to male fibromyalgia ratios that are widely described by expert sources [11–13]. We believe that such findings only occur in the presence of selection bias or biased ascertainment.

As unbiased epidemiological studies show only a small increase in the female to male sex ratio (~1.5:1) as opposed to the observed ratio in clinical studies of 9:1, we believe that the over-identification of fibromyalgia in women and the consequent under-identification of men is the result of bias.

• 2018, Characterizing classes of fibromyalgia within the continuum of central sensitization syndrome

FM is a disease continuum characterized by progressive and identifiable classifications. Four classes of FM can be differentiated by pain and symptom severity, specific comorbidities, and use of clinical procedures.

• 2018, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences

This commentary presents a simplified way of making the diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) using the 1994 Centers for Disease Control and Prevention case definition. The format used can easily be modified for other case definitions. The commentary then discusses whether ME/CFS is the same or a different illness from fibromyalgia. Because overlap exists between the 2 syndromes, some investigators have posited that they are variants of the same illness. I have viewed this as an empirically testable hypothesis and have summoned considerable amounts of data that suggest that the 2 illnesses differ. Were differences to exist, that would suggest different pathophysiologic processes for each, leading to different treatments.

• 2018, The neurobiology of central sensitization

• 2019, Metabolic fingerprinting for diagnosis of fibromyalgia and other rheumatologic disorders

A fibromyalgia blood test was the aim of the study by Hacksaw et al (2018), which looked for a fibromyalgia biomarker and found a unique metabolic fingerprint which distinguished all patients with fibromyalgia from those with systemic lupus erythematosus, rheumatoid arthritis and osteoarthritis. The study only analysed blood samples from rheumatic diseases, so it did not include patients with ME/CFS or other illnesses which can chronic pain.

• 2019, RETRACTED Is insulin resistance the cause of fibromyalgia? A preliminary report (Full text)

Retraction notice. :Retracted due to post-publication ethics approval and lack of gender, age and ethnic group controls in comparison group.

• 2019, A systematic review and meta-analysis of the prevalence of small fiber pathology in fibromyalgia: Implications for a new paradigm in fibromyalgia ethiopathogenesis

• 2019, Mixed exercise training for adults with fibromyalgia

• 2019, An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia

• 2019, Dietary interventions in fibromyalgia: a systematic review

• 2019, Low-Level Laser Therapy for Fibromyalgia: A Systematic Review and Meta-Analysis

• 2019, AAPT Diagnostic Criteria for Fibromyalgia

2020-2024

• 2020, Determining the association between fibromyalgia, the gut microbiome and its biomarkers: A systematic review
• 2020, A systematic review of the association between fibromyalgia and functional gastrointestinal disorders
• 2020, Investigating Fatigue and Exercise Intolerance in a University Immunology Clinic

• 2020, Fibromyalgia and obesity: A comprehensive systematic review and meta-analysis

• 2020, Comorbidities of self-reported fibromyalgia in United States adults: A cross-sectional study from The National Epidemiological Survey on Alcohol and Related Conditions (NESARC-III)

• 2020, Is Transcranial Direct Current Stimulation (tDCS) Effective for the Treatment of Pain in Fibromyalgia? A Systematic Review and Meta-Analysis

• 2020, Effects of transcranial direct current stimulation and transcranial magnetic stimulation in patients with fibromyalgia. A systematic review

See also

Transcranial direct current stimulation and Transcranial magnetic stimulation.

• 2021, Analysis of Retinal Layers in Fibromyalgia Patients with Premium Protocol in Optical Tomography Coherence and Quality of Life

A potential biomarker for fibromyalgia, using a non-invasive eye test.

• 2021, The Search for Biomarkers in Fibromyalgia
• 2021, Insulin Resistance is Associated with Central Pain in Patients with Fibromyalgia Observational Study - authors in common with the retracted 2019 insulin resistance study

Depression and anxiety

• 2008, The relationship between fibromyalgia and major depressive disorder: a comprehensive review (Abstract)
• 2010, Anxiety and depressive symptoms in fibromyalgia are related to poor perception of health but not to pain sensitivity or cerebral processing of pain (Abstract)
• 2012, Fibromyalgia a discrete entity? (Full text)

Psychological paradigm

• 2012, Personality and Fibromyalgia Syndrome (Full text)

Conclusion: No specific fibromyalgia personality is defined but it is proposed that personality is an important filter that modulates a person’s response to psychological stressors. Certain personalities may facilitate translation of these stressors to physiological responses driving the fibromyalgia mechanism.

• 2015, Brain "fog," inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin. (Full text)

• 2015, Hyperbaric Oxygen Therapy Can Diminish Fibromyalgia Syndrome (Full text)

See also

Hyperbaric oxygen therapy.

• 2016, Explaining unexplained pain to fibromyalgia patients: finding a narrative that is acceptable to patients and provides a rationale for evidence-based interventions (Full text)

• 2016, Fibromyalgia: A Short Commentary (Full text)

Grant awards and current research

• Oct 2016, Chronic pain researchers to expand work with $7.5M award from NIH
• Jun 2018, The Bateman Horne Center will be an All of Us recruitment center for people living with ME/CFS and fibromyalgia. All of Us is a ten year Precision Medicine Initiative project that has been funded $1.5 Billion to recruit one million patients for its bio-bank. The idea is to research all diseases, from the most common to the most rare while taking into account lifestyle, environment, and biology.

See also

• Fibromyalgia
• Fibromyalgia disability process
• Fibromyalgia drugs

central nervous system (CNS) - One of the two parts of the human nervous system, the other part being the peripheral nervous system. The central nervous system consists of the brain and spinal cord, while the peripheral nervous system consists of nerves that travel from the central nervous system into the various organs and tissues of the body.

etiology The cause of origin, especially of a disease.

neuroendocrine relating to hormones that influence the nervous system

neuroendocrine relating to hormones that influence the nervous system

Canadian Consensus Criteria (CCC) - A set of diagnostic criteria used to diagnose ME/CFS, developed by a group of practicing ME/CFS clinicians in 2003. The CCC is often considered to be the most complex criteria, but possibly the most accurate, with the lowest number of patients meeting the criteria. Led to the development of the International Consensus Criteria (ICC) in 2011.

cytokine any class of immunoregulatory proteins secreted by cells, especially immune cells. Cytokines are small proteins important in cell signaling that modulate the immune system. (Learn more: me-pedia.org)

T cell A type of white blood cell which is mostly produced or matured in the thymus gland (hence T-cell) and is involved in the adaptive immune response on a cellular level. Also known as a T lymphocyte. (Learn more: www.youtube.com)

bias Bias in research is "a systematic deviation of an observation from the true clinical state". (Learn more: me-pedia.org)

bias Bias in research is "a systematic deviation of an observation from the true clinical state". (Learn more: me-pedia.org)

cerebral 1. of or relating to the brain or the intellect 2. of, relating to, affecting, or being the cerebrum.

physiological Concerning living organisms, such as cells or the human body.  Physio logical (as in physio) is not to be confused with psych ological (emotional stress).

somatic symptom disorder A psychiatric term to describe an alleged condition whereby a person's thoughts somehow cause physical symptoms. The actual existence of such a condition is highly controversial, due to a lack of scientific evidence. It is related to other psychiatric terms, such as "psychosomatic", "neurasthenia", and "hysteria". Older terms include "somatization", "somatoform disorder", and "conversion disorder". Such terms refer to a scientifically-unsupported theory that claims that a wide range of physical symptoms can be created by the human mind, a theory which has been criticized as "mind over matter" parapsychology, a pseudoscience.