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Discovery by a proteomic approach of possible early biomarkers of drug-induced nephrotoxicity in medication-overuse headache.

ABSTRACT: Medication-overuse headache (MOH) is a chronic headache condition that results from the overuse of analgesics drugs, triptans, or other antimigraine compounds. The epidemiology of drug-induced disorders suggests that medication overuse could lead to nephrotoxicity, particularly in chronic patients. The aim of this work was to confirm and extend the results obtained from a previous study, in which we analyzed the urinary proteome of 3 MOH patients groups: non-steroidal anti-inflammatory drugs (NSAIDs), triptans and mixtures abusers, in comparison with non-abusers individuals (controls).In the present work we employed specialized proteomic techniques, namely two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry (MS), and the innovative Surface-Enhanced Laser Desorption/Ionization Time-of-Flight mass spectrometry (SELDI-TOF-MS), to discover characteristic proteomic profiles associated with MOH condition.By 2-DE and MS analysis we identified 21 over-excreted proteins in MOH patients, particularly in NSAIDs abusers, and the majority of these proteins were involved in a variety of renal impairments, as resulted from a literature search. Urine protein profiles generated by SELDI-TOF-MS analysis showed different spectra among groups. Moreover, significantly higher number of total protein spots and protein peaks were detected in NSAIDs and mixtures abusers.These findings confirm the presence of alterations in proteins excretion in MOH patients. Analysis of urinary proteins by powerful proteomic technologies could lead to the discovery of early candidate biomarkers, that might allow to identify MOH patients prone to develop potential drug overuse-induced nephrotoxicity.

SUBMITTER: Bellei E

PROVIDER: S-EPMC3606963 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Discovery by a proteomic approach of possible early biomarkers of drug-induced nephrotoxicity in medication-overuse headache.

Bellei Elisa E Monari Emanuela E Cuoghi Aurora A Bergamini Stefania S Guerzoni Simona S Ciccarese Michela M Ozben Tomris T Tomasi Aldo A Pini Luigi Alberto LA

The journal of headache and pain 20130130

<h4>Background</h4>Medication-overuse headache (MOH) is a chronic headache condition that results from the overuse of analgesics drugs, triptans, or other antimigraine compounds. The epidemiology of drug-induced disorders suggests that medication overuse could lead to nephrotoxicity, particularly in chronic patients. The aim of this work was to confirm and extend the results obtained from a previous study, in which we analyzed the urinary proteome of 3 MOH patients groups: non-steroidal anti-inf ...[more]

PMID: 23565828

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Project description:BACKGROUND AND AIMS:Medication-overuse headache (MOH) is a common chronic headache caused by overuse of headache analgesics. It has similarities with substance dependence disorders. The treatment of choice for MOH is withdrawal of the offending analgesics. Behavioral brief intervention treatment using methods adapted from substance misuse settings is effective. Here we investigate the severity of analgesics dependence in MOH using the Severity of Dependence Scale (SDS), validate the SDS score against formal substance dependence diagnosis based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) and examine whether the SDS predicts successful withdrawal. METHODS:Representative recruitment from the general population; 60 MOH patients, 15 chronic headache patients without medication overuse and 25 population controls. Headaches were diagnosed using the International Classification of Headache Disorders, medication use was assessed and substance dependence classified according to the DSM-IV. The SDS was scored by interviewers blinded to patient group. Descriptive statistics were used and validity of the SDS score assessed against a substance dependence diagnosis using ROC analysis. RESULTS:Sixty-two percent of MOH patients overused simple analgesics, 38% centrally acting analgesics (codeine, opiates, triptans). Fifty percent of MOH patients were classified as DSM-IV substance dependent. Centrally active medication and high SDS scores were associated with higher proportions of dependence. ROC analysis showed SDS scores accurately identified dependence (area under curve 88%). Lower SDS scores were associated with successful withdrawal (P = 0.004). CONCLUSIONS:MOH has characteristics of substance dependence which should be taken into account when choosing treatment strategy. TRIAL REGISTRATION:Based on data collected in previously reported randomized BIMOH trial (; in the present manuscript, Clinical trials registration number: NCT01314768). The present part, however, represents observational data and is not a treatment trial.

Project description:ObjectiveTo estimate the relative frequency of acute medication overuse (AMO) among people with episodic migraine and chronic migraine, to characterize the types of acute medications overused for migraine, and to identify factors associated with AMO.MethodsWe analyzed data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study (ClinicalTrials.gov, NCT01648530), a cross-sectional and longitudinal internet study that included a systematic sampling of the US population. From September 2012 to November 2013, the CaMEO Study respondents participated in different modules to collect data on the clinical course of migraine, family burden, barriers to care, endophenotypes, and comorbidities. Among people who met the criteria for migraine consistent with the International Classification of Headache Disorders, third edition (ICHD-3), we evaluated types and frequency of medications used for headache/migraine, selected comorbidities, and emergency department (ED) and urgent care (UC) use. AMO was defined by days per month of medication use as specified by ICHD-3 criteria for medication overuse headache (MOH) without the requirement for ≥15 monthly headache days (MHDs). Nested, multivariable binary logistic regression modeling was used to identify factors associated with an increased risk of AMO.ResultsOf 16,789 CaMEO respondents with migraine, 2,975 (17.7%) met the AMO criteria. Approximately 67.9% (2,021/2,975) of AMO respondents reported <15 MHDs. Simple analgesics, combination analgesics, and opioids were the medication classes most commonly overused. Factors associated with AMO in the final multivariable logistic regression model included ≥15 MHDs, moderate to severe disability, severe migraine interictal burden, use of preventive medication, and an ED/UC visit for headache within 6 months.ConclusionsApproximately two-thirds of respondents with AMO reported <15 MHDs and therefore did not meet the criteria for MOH. Those with AMO had greater disease burden and increased ED/UC utilization relative to people with migraine but not AMO.

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Discovery by a proteomic approach of possible early biomarkers of drug-induced nephrotoxicity in medication-overuse headache.

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Discovery by a proteomic approach of possible early biomarkers of drug-induced nephrotoxicity in medication-overuse headache.

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