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Passive transfer of fibromyalgia symptoms from patients to mice.

ABSTRACT: Fibromyalgia syndrome (FMS) is characterized by widespread pain and tenderness, and patients typically experience fatigue and emotional distress. The etiology and pathophysiology of fibromyalgia are not fully explained and there are no effective drug treatments. Here we show that IgG from FMS patients produced sensory hypersensitivity by sensitizing nociceptive neurons. Mice treated with IgG from FMS patients displayed increased sensitivity to noxious mechanical and cold stimulation, and nociceptive fibers in skin-nerve preparations from mice treated with FMS IgG displayed an increased responsiveness to cold and mechanical stimulation. These mice also displayed reduced locomotor activity, reduced paw grip strength, and a loss of intraepidermal innervation. In contrast, transfer of IgG-depleted serum from FMS patients or IgG from healthy control subjects had no effect. Patient IgG did not activate naive sensory neurons directly. IgG from FMS patients labeled satellite glial cells and neurons in vivo and in vitro, as well as myelinated fiber tracts and a small number of macrophages and endothelial cells in mouse dorsal root ganglia (DRG), but no cells in the spinal cord. Furthermore, FMS IgG bound to human DRG. Our results demonstrate that IgG from FMS patients produces painful sensory hypersensitivities by sensitizing peripheral nociceptive afferents and suggest that therapies reducing patient IgG titers may be effective for fibromyalgia.

SUBMITTER: Goebel A

PROVIDER: S-EPMC8245181 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Passive transfer of fibromyalgia symptoms from patients to mice.

Goebel Andreas A Krock Emerson E Gentry Clive C Israel Mathilde R MR Jurczak Alexandra A Urbina Carlos Morado CM Sandor Katalin K Vastani Nisha N Maurer Margot M Cuhadar Ulku U Sensi Serena S Nomura Yuki Y Menezes Joana J Baharpoor Azar A Brieskorn Louisa L Sandström Angelica A Tour Jeanette J Kadetoff Diana D Haglund Lisbet L Kosek Eva E Bevan Stuart S Svensson Camilla I CI Andersson David A DA

The Journal of clinical investigation 20210701 13

Fibromyalgia syndrome (FMS) is characterized by widespread pain and tenderness, and patients typically experience fatigue and emotional distress. The etiology and pathophysiology of fibromyalgia are not fully explained and there are no effective drug treatments. Here we show that IgG from FMS patients produced sensory hypersensitivity by sensitizing nociceptive neurons. Mice treated with IgG from FMS patients displayed increased sensitivity to noxious mechanical and cold stimulation, and nocicep ...[more]

PMID: 34196305

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Project description:BackgroundFibromyalgia (FM) patients frequently complain of cognitive problems, but it remains unclear whether these cognitive complaints can be attributed to a dysfunction of the central nervous system or if they can be explained by other factors associated with the disease, such as depression, anxiety and sleep dysfunction.MethodsOne hundred and ten patients with FM were compared with thirty-three patients diagnosed with a depressive disorder (DD) and fifty healthy controls (HC). Several measures of attention and executive functions were used to make these comparisons and the patients were also asked to complete questionnaires on depression, anxiety and sleep quality. Univariate analyses of covariance (ANCOVA) were performed to identify and control confounders and multiple linear models were used to examine the effects of fibromyalgia and depression on cognitive measures.ResultsFM and HC differed significantly with respect to depression, anxiety and sleep dysfunction, whereas FM and DD did not differ in terms of symptoms of depression and anxiety. However, FM was associated with a worse quality of sleep than DD. Comparisons of cognitive performance between groups showed that short-term and working memory and inattention measures were only associated with symptoms of depression, whereas selective attention was associated with both depression and fibromyalgia, and processing speed, cognitive flexibility and inhibitory control showed a significant interaction between depression and fibromyalgia. Moreover, cognitive flexibility and inhibition abilities were specifically associated with FM.ConclusionFM patients show a cluster of cognitive impairment in the attentional and executive domains, although some of the symptoms observed could be explained by the severity of the symptoms of depression, while others seem to depend on the effects of fibromyalgia. Implications of the findings for the understanding and management of cognitive impairment of FM patients are discussed.

Project description:ObjectiveSeveral epidemiological and clinical reports associate fibromyalgia (FM) with seizure disorders, and clinical studies associate FM diagnosis with psychogenic non-epileptic seizures. However, these associations rely on self-reports of being diagnosed with FM or unstandardized clinical diagnosis in combination with small samples. We investigated the association of FM and self-reported seizures using a large rheumatic disease databank and the current established self-reported, symptom-based FM diagnostic criteria.MethodsWe selected a random observation from 11,378 subjects with rheumatoid arthritis (RA), 2,390 (21.0%) of whom satisfied 2016 revised criteria for FM. Patients were inquired about the presence of any kind of seizures in the previous 6 months, anti-epileptic medications, and patient-reported symptoms and outcomes.ResultsSeizures were reported by 89 RA patients who met FM criteria (FM+) and by 97 patients who did not (FM-), resulting in an age- and sex-adjusted seizure prevalence of 3.74 (95% CI 2.95 to 4.53) per 100 FM+ subjects and 1.08 (95% CI 0.87 to 1.30) in FM- subjects. The seizure odds ratio of FM+ to FM- cases was 3.54 (95% CI 2.65 to 4.74). Seizures were associated to a very similar degree with symptom reporting (somatic symptom count and comorbidity index) as to FM diagnosis variables. RA patients reporting seizures also reported worse pain, quality of life, and functional status. Seizure patients treated with anti-seizure medication had worse outcomes and more comorbidities than seizure patients with no seizure drugs.ConclusionsWe found a significant and similar association of both FM diagnostic variables and FM-related symptom variables, including the number of symptoms and comorbidities, with self-reported seizures in people with RA. The observed association was similar to those found in previous studies of symptoms variables and seizures and does not suggest a unique role for fibromyalgia diagnosis. Rather, it suggests that multi-symptom comorbidity is linked to seizures in a complex and not yet clearly understood way. As the current study relied on self-reported seizures and was not able to distinguish between epileptic and psychogenic nonepileptic seizures, future studies are needed to replicate the findings using both validated FM criteria assessments and clinically verified diagnoses of epileptic and psychogenic seizures.

Project description:PurposeTo describe and evaluate somatic symptoms in patients with rheumatoid arthritis (RA) and fibromyalgia, determine the relation between somatization syndromes and fibromyalgia, and evaluate symptom data in light of the Diagnostic and Statistical Manual-5 (DSM-5) criteria for somatic symptom disorder.MethodsWe administered the Patient Health Questionnaire-15 (PHQ-15), a measure of somatic symptom severity to 6,233 persons with fibromyalgia, RA, and osteoarthritis. PHQ-15 scores of 5, 10, and 15 represent low, medium, and high somatic symptom severity cut-points. A likely somatization syndrome was diagnosed when PHQ-15 score was ≥10. The intensity of fibromyalgia diagnostic symptoms was measured by the polysymptomatic distress (PSD) scale.Results26.4% of RA patients and 88.9% with fibromyalgia had PHQ-15 scores ≥10 compared with 9.3% in the general population. With each step-wise increase in PHQ-15 category, more abnormal mental and physical health status scores were observed. RA patients satisfying fibromyalgia criteria increased from 1.2% in the PHQ-15 low category to 88.9% in the high category. The sensitivity and specificity of PHQ-15≥10 for fibromyalgia diagnosis was 80.9% and 80.0% (correctly classified = 80.3%) compared with 84.3% and 93.7% (correctly classified = 91.7%) for the PSD scale. 51.4% of fibromyalgia patients and 14.8% with RA had fatigue, sleep or cognitive problems that were severe, continuous, and life-disturbing; and almost all fibromyalgia patients had severe impairments of function and quality of life.ConclusionsAll patients with fibromyalgia will satisfy the DSM-5 "A" criterion for distressing somatic symptoms, and most would seem to satisfy DSM-5 "B" criterion because symptom impact is life-disturbing or associated with substantial impairment of function and quality of life. But the "B" designation requires special knowledge that symptoms are "disproportionate" or "excessive," something that is uncertain and controversial. The reliability and validity of DSM-5 criteria in this population is likely to be low.

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Passive transfer of fibromyalgia symptoms from patients to mice.

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Passive transfer of fibromyalgia symptoms from patients to mice.

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