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

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.Medication-overuse headache (MOH) is a secondary cause of chronic daily headache, where headaches occur 15 or more days per month when the therapeutic agent is used excessively and on a regular basis for 3 or more months, and when headaches have developed or markedly worsened during the period of medication overuse [1]. Approximately 40% of all patients attending Headache Centers presents a chronic form of headache and 80% of these subjects excessively use symptomatic drugs which include analgesics, migraine-specific medications (such as triptans), opioids, or drugs combinations [2]. Although MOH has a prevalence of 1-2% in the general population, it represents a relevant health problem associated with significant long-term morbidity and disability [3]. MOH manifests as increased frequency and intensity of migraine attacks and as enhanced sensitivity to stimuli that elici