Identification of candidate proteomic markers in the serum of medication overuse headache patients: An exploratory study

Abstract

Purpose of the study The pathophysiological mechanism of medication overuse headache is uncertain; no distinctive markers have been described right now. The aim of this study was to conduct proteomic analyses on serum samples from patients with medication overuse headache and healthy individuals. Specifically, mono- (SDS-PAGE) and two-dimensional gel electrophoresis (2-DE) followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) were used to evaluate changes in serum proteins. Main findings By SDS-PAGE, four over-expressed bands were revealed in patients, compared to controls. 2-DE combined with LC-MS/MS analysis allowed confirmation of some proteins preliminarily detected by SDS-PAGE: Hemopexin, alpha-1-acid glycoprotein 1, apolipoprotein A4 and haptoglobin. Moreover, other differential proteins were isolated, mostly increased in MOH patients: Alpha-1-antitrypsin, immunoglobulin heavy constant alpha 1, retinol binding protein and transthyretin. Only one protein, immunoglobulin kappa constant, was decreased in the patients’ group. Conclusions The investigation of the serum proteome can offer a better understanding about biological mechanisms underlying medication overuse headache. Specifically, medication overuse headache shares some serum biochemical markers with chronic pain conditions. Further studies might uncover the relevance of these proteins in medication overuse headache.

Urinary Proteomics Reveals Promising Biomarkers in Menstrually Related and Post-Menopause Migraine

“…Only two proteins were down-regulated in both MM and PM groups compared to CTRL: APOA1 ( Figure 4 F), a negative acute phase protein implicated in cholesterol transport and lipid metabolism, and A1AT, the most abundant circulating serine proteinase inhibitor, with a duplex immunomodulatory and anti-inflammatory function. Similarly, a deficiency of A1AT has been documented in patients with cluster headache [ 41 ], while it was increased in serum of MOH patients [ 16 ] and PM women [ 18 ]. The high presence of A1AT in serum samples could reflect and explain the low levels found in urine.…”

“…This system is involved in inflammatory-like responses during the normal functions of the ovary and uterus, which seem to be regulated by estrogen [ 25 ]. Increased KNG1 levels were also detected in serum of MOH patients vs. non-headache controls [ 16 ]. Therefore, these results contribute to enhance the hypothesis about a reasonable activation of the inflammatory system in MM.…”

“…Both UROM and AMBP were further demonstrated to be increased by western blot analysis ( Figure 4 B and Figure 4 C, respectively). Moreover, they were previously found over-expressed in urine [ 12 , 13 , 14 ] and serum [ 16 ] of MOH patients and MM and PM women [ 18 ]. Based on their involvement in immune and inflammatory processes, these proteins found to be increased in PM women may be hypothetical biomarkers of the migraine permanence even after menopause.…”

“…SDS-PAGE was performed under reducing conditions according to the Laemmli’s method, as previously described [ 16 ]. Pooled urinary samples (5 pools per group) were diluted 1:1 with the Laemmli sample buffer added of 20% 2-mercaptoethanol (Merck KGaA, Darmstadt, Germany) and heated at 95 °C for 5 min.…”

“…However, at present, few proteomics studies have been developed in the attempt to identify promising biomarkers and new physiopathological pathways associated with migraine and other types of headache disorders. In the last few years, our group widely investigated the medication-overuse headache (MOH) by proteomics, to discover candidate urinary biomarkers of drug-induced nephrotoxicity [ 12 , 13 ] and allodynia [ 14 ], as well as serum targets of chronic pain in MOH patients [ 15 , 16 ] and in an animal model of chronic neuropathic pain [ 17 ]. Moreover, we have examined the serum proteome of female suffering from MM and PM, in the search of potential serum biomarkers [ 18 ].…”