Abstract
Medication-overuse headache (MOH) is a chronic disorder associated with overuse of analgesic drugs, triptans, non-steroidal anti-inflammatory drugs (NSAIDs) or other acute headache compounds. Various epidemiologic investigations proved that different drug types could cause nephrotoxicity, particularly in chronic patients. The aim of the present work was to analyze, by a proteomic approach, the urinary protein profiles of MOH patients focusing on daily use of NSAIDs, mixtures and triptans that could reasonably be related to potential renal damage. We selected 43 MOH patients overusing triptans (n = 18), NSAIDs (n = 11), and mixtures (n = 14), for 2–30 years with a mean daily analgesic intake of 1.5 ± 0.9 doses, and a control group composed of 16 healthy volunteers. Urine proteins were analyzed by mono-dimensional gel electrophoresis and identified by mass spectrometry analysis. Comparing the proteomic profiles of patients and controls, we found a significantly different protein expression, especially in the NSAIDs group, in which seven proteins resulted over-secreted from kidney (OR = 49, 95% CI 2.53–948.67 vs. controls; OR = 11.6, 95% CI 0.92–147.57 vs. triptans and mixtures groups). Six of these proteins (uromodulin, α-1-microglobulin, zinc-α-2-glycoprotein, cystatin C, Ig-kappa-chain, and inter-α-trypsin heavy chain H4) were strongly correlated with various forms of kidney disorders. Otherwise, in mixtures and in triptans abusers, only three proteins were potentially associated to pathological conditions (OR = 4.2, 95% CI 0.33–53.12, vs. controls). In conclusion, this preliminary proteomic study allowed us to define the urinary protein pattern of MOH patients that is related to the abused drug. According with the obtained results, we believe that the risk of nephrotoxicity should be considered particularly in MOH patients who abuse of NSAIDs.
Highlights
The aim of the present work was to analyze, by a proteomic approach, the urinary protein profiles of Medication-overuse headache (MOH) patients focusing on daily use of non-steroidal anti-inflammatory drugs (NSAIDs), mixtures and triptans that could reasonably be related to potential renal damage
Comparing the proteomic profiles of patients and controls, we found a significantly different protein expression, especially in the NSAIDs group, in which seven proteins resulted over-secreted from kidney (OR = 49, 95% CI 2.53–948.67 vs. controls; Odds ratio (OR) = 11.6, 95% CI 0.92–147.57 vs. triptans and mixtures groups)
The term medication-overuse headache (MOH) was recently introduced by the International Headache Society to describe daily or nearly daily headache that occurs after the regular intake of analgesic drugs, triptans, or other anti-headache or anti-migraine drugs [1, 2]; their excessive use for the treatment of pain conditions led to the development of MOH in about 1.7% of the people in Europe, Asia, and North America [3]
Summary
The term medication-overuse headache (MOH) was recently introduced by the International Headache Society to describe daily or nearly daily (chronic) headache that occurs after the regular intake (overuse) of analgesic drugs, triptans, or other anti-headache or anti-migraine drugs [1, 2]; their excessive use for the treatment of pain conditions led to the development of MOH in about 1.7% of the people in Europe, Asia, and North America [3].The molecular basis and the pathophysiology of MOH are still largely unknown, it has been hypothesized that this condition could be mediated by cognitive impulsivity, and shares some dysfunction mechanisms with drug addiction [4], probably involving factors beyond the pain alone, such as certain behaviors and psychologic states [5]. An involvement of the serotonin transporter gene in the development of analgesics overuse in chronic tension-type headache patients has been postulated [10]. Human urine is a useful biologic fluid for clinical proteomics study, as it can be collected and non-invasively in large quantities, and because it is a stable sample compared with other biofluids. It has been defined as a fluid biopsy of the kidney and urogenital tract, so many changes in these organs may be detected in urine [14, 15]. Urinary proteomics has become one of the most attractive subdisciplines in clinical proteomics, for biomarker discovery [16] and clinical diagnostics [17]
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