Abstract

BackgroundMedication Overuse Headache (MOH) is a prevalent and disabling disorder resulting from the overuse of analgesic drugs, triptans or other acute headache medications. In previous proteomic studies, several proteins have been found at high concentrations in the urine of MOH patients and in the serum of rats with neuropathic pain. The aim of this study was to compare the serum levels of lipocalin-type Prostaglandin D2 synthase (L-PGDS), Vitamin D-binding protein (VDBP), apolipoprotein E (APOE) and apolipoprotein A1 (APOA1) in MOH patients and healthy individuals, further exploring their relationship with cutaneous pain thresholds (CPTs) in the territories innervated by the trigeminal nerve.MethodsSixty-nine MOH patients and 42 age- and sex-matched healthy volunteers were enrolled in the study. Von Frey-like filaments were applied to the skin territories innervated by the trigeminal nerve, to determine the CPTs. L-PGDS, VDBP, APOE and APOA1 were quantified in the serum by Enzyme-linked Immunosorbent Assay (ELISA). Clinical and laboratory data were collected. Comparisons between MOH patients and healthy individuals were performed using independent t test or χ2 test. To correlate serum proteins with CPTs, Pearson correlation coefficient or Spearman’s rank correlation coefficient were used.ResultsCPTs were lower among MOH patients. L-PGDS, VDBP and APOE had significantly different serum concentrations between groups (p < 0.01), but no correlation was found with CPTs. APOA1 serum concentrations did not differ between patients and healthy individuals.ConclusionsL-PGDS, VDBP and APOE had abnormal serum levels in MOH patients, confirming their alteration in some conditions of chronic headache and neuropathic pain. However, they had no relationship with CPTs. The in-depth study of serum proteins represents a promising approach for a better understanding of MOH, as well as the detection of candidate biomarkers for chronic headache or the risks associated with overuse medications.

Highlights

  • Medication Overuse Headache (MOH) is a prevalent and disabling disorder resulting from the overuse of analgesic drugs, triptans or other acute headache medications

  • MOH may complicate the majority of primary headaches and it can be caused by several acute headache medications, including migraine-specific and nonspecific drugs

  • Assuming that some pathophysiological processes may be shared between MOH and neuropathic pain, the primary objective of this study was to quantify and compare the serum levels of lipocalin-type Prostaglandin D2 synthase (L-PGDS), Vitamin D-binding protein (VDBP), apolipoprotein E (APOE) and apolipoprotein A1 (APOA1), as well as the cutaneous pain thresholds (CPTs) in the territories innervated by the trigeminal nerve in MOH patients and healthy individuals as control group

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Summary

Introduction

Medication Overuse Headache (MOH) is a prevalent and disabling disorder resulting from the overuse of analgesic drugs, triptans or other acute headache medications. Chronic pain (CP) is a major health care problem. It affects approximately 20% of the European population [1], and gives considerable costs to the society, more than heart diseases, cancer and diabetes put together [2]. The almost daily intake of acute headache medications can paradoxically worsen the chronic symptoms, leading to a secondary headache named medication-overuse headache (MOH) [8]. MOH may complicate the majority of primary headaches and it can be caused by several acute headache medications, including migraine-specific (triptans and ergotamine) and nonspecific (nonsteroidal antiinflammatory drugs or NSAIDs, paracetamol, opioids and combinations of analgesics or mixture) drugs. The only proposed was cutaneous allodynia (CA) [12], defined as pain resulting from an innocuous stimulus to normal skin

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