Abstract
BackgroundFibromyalgia syndrome (FMS) is a chronic pain syndrome. A plausible pathogenesis of the disease is uncertain and the pursuit of measurable biomarkers for objective identification of affected individuals is a continuing endeavour in FMS research. Our objective was to perform an explorative metabolomics study (1) to elucidate the global urinary metabolite profile of patients suffering from FMS, and (2) to explore the potential of this metabolite information to augment existing medical practice in diagnosing the disease.MethodsWe selected patients with a medical history of persistent FMS (n = 18), who described their recent state of the disease through the Fibromyalgia Impact Questionnaire (FIQR) and an in-house clinical questionnaire (IHCQ). Three control groups were used: first-generation family members of the patients (n = 11), age-related individuals without any indications of FMS or related conditions (n = 10), and healthy young (18–22 years) individuals (n = 20). All subjects were female and the biofluid under investigation was urine. Correlation analysis of the FIQR showed the FMS patients represented a well-defined disease group for this metabolomics study. Spectral analyses of urine were conducted using a 500 MHz 1H nuclear magnetic resonance (NMR) spectrometer; data processing and analyses were performed using Matlab, R, SPSS and SAS software.Results and discussionUnsupervised and supervised multivariate analyses distinguished all three control groups and the FMS patients, and significant increases in metabolites related to the gut microbiome (hippuric, succinic and lactic acids) were observed. We have developed an algorithm for the diagnosis of FMS consisting of three metabolites — succinic acid, taurine and creatine — that have a good level of diagnostic accuracy (Receiver Operating Characteristic (ROC) analysis — area under the curve 90%) and on the pain and fatigue symptoms for the selected FMS patient group.ConclusionOur data and comparative analyses indicated an altered metabolic profile of patients with FMS, analytically detectable within their urine. Validation studies may substantiate urinary metabolites to supplement information from medical assessment, tender-point measurements and FIQR questionnaires for an improved objective diagnosis of FMS.
Highlights
Fibromyalgia syndrome (FMS) is a chronic pain syndrome
To characterize further the relationship between questions or variables making up the Fibromyalgia Impact Questionnaire (FIQR) questionnaire, we calculated Kendall’s tau correlation coefficients for the FMS patient group (Fig. 1)
We conclude the FMS patients represent a well-defined group for this explorative metabolomics study
Summary
Fibromyalgia syndrome (FMS) is a chronic pain syndrome. A plausible pathogenesis of the disease is uncertain and the pursuit of measurable biomarkers for objective identification of affected individuals is a continuing endeavour in FMS research. Fibromyalgia syndrome (FMS) is a common chronic pain syndrome characterized by widespread musculoskeletal pain and associated with multiple other symptoms such as cognitive impairment, disrupted sleep and chronic fatigue. The American College of Rheumtology (ACR) first published criteria for FMS in 1990 [1] which emphasized chronic widespread musculo-skeletal pain (including pain in the axial skeleton) in the presence of pain on at least 11 of 18 specified tender point sites with digital palpation of 4 kg/cm. FMS is currently viewed as a central sensitivity syndrome associated with abnormal pain processing. It is regarded as a “pain amplification syndrome” associated with increased sensitivity of the nervous system and decreased anti-nociception which results in the clinical phenomena of hyperalgesia and allodynia. Dysfunction in central mono-aminergic neurotransmission which involves serotonin, norepinephrine, nerve growth factor, substance P and others have been implicated in the patho-physiology of FMS. [5,6,7,8] FMS patients often have associated comorbidities such as irritable bowel syndrome, interstitial cystitis and mood disorders [9, 10]
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