Proteomic analysis of urine in medication-overuse headache patients: possible relation with renal damages.

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.

• Authors: Elisa Bellei, Aurora Cuoghi, Emanuela Monari, Stefania Bergamini, Luca Isaia Fantoni, Maurizio Zappaterra, Simona Guerzoni, Annalisa Bazzocchi, Aldo Tomasi, Luigi Alberto Pini
• Journal: The journal of headache and pain (J Headache Pain) Vol. 13 Issue 1 Pg. 45-52 (Jan 2012) ISSN: 1129-2377 [Electronic] England
• PMID: 21997203 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics

Topics

• Adult
• Aged
• Analgesics (adverse effects)
• Comet Assay
• Female
• Headache (chemically induced, urine)
• Humans
• Kidney Diseases (chemically induced, urine)
• Male
• Mass Spectrometry
• Middle Aged
• Proteomics