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

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.

A case-control study of visually evoked postural responses in childhood with primary headaches.

BACKGROUND: Disorientation, nausea, confusion, dizziness, and displacement are frequently complained by headache-suffering children. Anyhow, the cause of these symptoms is still unclear, and a dysfunction of vestibular pathways or their alteration due to central pain pathways hyper-activation, has been proposed. The aim of this study is to use posturography to explore the balance function of headache-suffering children during pain-free periods. METHODS: Posturography was performed on 19 migraineurs, 11 tension-type headache sufferers, and 20 healthy controls. Posturographic measures were performed during headache-free periods under different conditions: with eyes opened, eyes closed, and during right and left optokinetic stimulation. The last 2 conditions were used to mimic unreliable visual signals that can confound vestibular system. RESULTS: During eyes-closed conditions, headache-suffering children displayed higher displacements than healthy controls, since statokinesiogram surface was higher in tension-type headache sufferers and migraineurs compared with controls (P value = 0.0095). Romberg's index, indicating the overall stability of the subject, was lower in healthy controls than in headache sufferers (P = 0.0139), thus suggesting a vestibular impairment in the seconds. Moreover, both during right and left optokinetic stimulation, the statokinesiogram length was higher in headache-suffering children (P < 0.0001). Thereafter, statokinesiogram surface was higher in migraineurs during right optokinetic stimulation (P = 0.0388) than in tension-type headache sufferers when stimulation was directed on the opposite side (P = 0.0249). CONCLUSIONS: These results suggest a central alteration of vestibular pathways in headache-suffering children, that makes balance function more dependent from visual inputs than healthy subjects, even in inter-ictal phases.

Exploration of candidate serum biomarkers potentially related to the chronic pain condition in Medication-overuse headache.

BACKGROUND: Medication 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. METHODS: Sixty-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. RESULTS: CPTs 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. CONCLUSIONS: L-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.

Nabilone administration in refractory chronic diarrhea: a case series.

BACKGROUND: Daily cannabis assumption is currently associated with several physical and mental health problems, however in the past it was prescribed for a multitude of symptoms, including vomiting, abdominal pain and diarrhea. Through the years, the endocannabinoid system has been recognized in the homeostatic mechanisms of the gut, as well as in the physiological control of intestinal motility and secretion. Accordingly, cannabinoids may be a promising therapy against several gastrointestinal conditions, such as abdominal pain and motility-related disorders. CASE PRESENTATION: We retrospectively analysed the efficacy and safety of a CB1-receptor agonist administered in six patients with refractory chronic diarrhea, between April 2008 and July 2016. After three months of therapy, oral nabilone improved the health of nearly all patients, with visible improvements in reducing diarrheal symptoms and weight gain. Most of the benefits persisted through the three-month follow-up. Only one patient interrupted the treatment after one month, due to severe fatigue and mental confusion; the symptoms disappeared in the follow-up period. CONCLUSIONS: These findings encourage the study of cannabinoids acting on CB1 receptors in chronic gastrointestinal disorders, especially in refractory chronic diarrhea, offering a chance for a substantial improvement in the quality of life of selected patients, with a reasonable safety profile.

Current and emerging evidence-based treatment options in chronic migraine: a narrative review.

BACKGROUND: Chronic migraine is a disabling condition that is currently underdiagnosed and undertreated. In this narrative review, we discuss the future of chronic migraine management in relation to recent progress in evidence-based pharmacological treatment. FINDINGS: Patients with chronic migraine require prophylactic therapy to reduce the frequency of migraine attacks, but the only currently available evidence-based prophylactic treatment options for chronic migraine are topiramate and onabotulinumtoxinA. Improved prophylactic therapy is needed to reduce the high burden of chronic migraine in Italy. Monoclonal antibodies that target the calcitonin gene-related peptide (CGRP) pathway of migraine pathogenesis have been specifically developed for the prophylactic treatment of chronic migraine. These anti-CGRP/R monoclonal antibodies have demonstrated good efficacy and excellent tolerability in phase II and III clinical trials, and offer new hope to patients who are currently not taking any prophylactic therapy or not benefitting from their current treatment. CONCLUSIONS: Treatment of chronic migraine is a dynamic and rapidly advancing area of research. New developments in this field have the potential to improve the diagnosis and provide more individualised treatments for this condition. Establishing a culture of prevention is essential for reducing the personal, social and economic burden of chronic migraine.

Development and validation of the ID-EC - the ITALIAN version of the identify chronic migraine.

BACKGROUND: Case-finding tools, such as the Identify Chronic Migraine (ID-CM) questionnaire, can improve detection of CM and alleviate its significant societal burden. We aimed to develop and validate the Italian version of the ID-CM (ID-EC) in paper and as a smart app version in a headache clinic-based setting. METHODS: The study investigators translated and adapted to the Italian language the original ID-CM questionnaire (ID-EC) and further implemented it as a smart app. The ID-EC was tested in its paper and electronic version in consecutive patients referring to 9 Italian tertiary headache centers for their first in-person visit. The scoring algorithm of the ID-EC paper version was applied by the study investigators (case-finding) and by patients (self-diagnosis), while the smart app provided to patients automatically the diagnosis. Diagnostic accuracy of the ID-EC was assessed by matching the questionnaire results with the interview-based diagnoses performed by the headache specialists during the visit according to the criteria of International Classification of Headache Disorders, III edition, beta version. RESULTS: We enrolled 531 patients in the test of the paper version of ID-EC and 427 in the validation study of the smart app. According to the clinical diagnosis 209 patients had CM in the paper version study and 202 had CM in the smart app study. 79.5% of patients returned valid paper questionnaires, while 100% of patients returned valid and complete smart app questionnaires. The paper questionnaire had a 81.5% sensitivity and a 81.1% specificity for case-finding and a 30.7% sensitivity and 90.7% specificity for self-diagnosis, while the smart app had a 64.9% sensitivity and 90.2% specificity. CONCLUSIONS: Our data suggest that the ID-EC, developed and validated in tertiary headache centers, is a valid case-finding tool for CM, with sensitivity and specificity values above 80% in paper form, while the ID-EC smart app is more useful to exclude CM diagnosis in case of a negative result. Further studies are warranted to assess the diagnostic accuracy of the ID-EC in general practice and population-based settings.

Drug-drug interactions in the treatment for alcohol use disorders: A comprehensive review.

Drug interactions are one of the most common causes of side effects in polypharmacy. Alcoholics are a category of patients at high risk of pharmacological interactions, due to the presence of comorbidities, the concomitant intake of several medications and the pharmacokinetic and pharmacodynamic interferences of ethanol. However, the data available on this issue are limited. These reasons often frighten clinicians when prescribing appropriate pharmacological therapies for alcohol use disorder (AUD), where less than 15% of patients receive an appropriate treatment in the most severe forms. The data available in literature regarding the relevant drug-drug interactions of the medications currently approved in United States and in some European countries for the treatment of AUD (benzodiazepines, acamprosate, baclofen, disulfiram, nalmefene, naltrexone and sodium oxybate) are reviewed here. The class of benzodiazepines and disulfiram are involved in numerous pharmacological interactions, while they are not conspicuous for acamprosate. The other drugs are relatively safe for pharmacological interactions, excluding the opioid withdrawal syndrome caused by the combination of nalmefene or naltrexone with an opiate medication. The information obtained is designed to help clinicians in understanding and managing the pharmacological interactions in AUDs, especially in patients under multi-drug treatment, in order to reduce the risk of a negative interaction and to improve the treatment outcomes.

Pharmacokinetics and tolerability of oral cannabis preparations in patients with medication overuse headache (MOH)-a pilot study.

PURPOSE: The recent release of a medical cannabis strain has given a new impulse for the study of cannabis in Italy. The National Health Service advises to consume medical cannabis by vaporizing, in decoction or oil form. This is the first study that explores the pharmacokinetics and tolerability of a single oral dose of cannabis as decoction (200 ml) or in olive oil (1 ml), as a first step to improve the prescriptive recommendations. METHODS: This is a single-center, open-label, two-period crossover study designed to assess the pharmacokinetics and tolerability of oral cannabis administered to 13 patients with medication overuse headache (MOH). A liquid chromatography tandem-mass spectrometry (LC-MS/MS) method was conducted for the quantification of THC, CBD, 11-OH-THC, THC-COOH, THC-COOH-glucuronide, THCA-A, and CBDA. Blood pressure, heart rate, and a short list of symptoms by numerical rating scale (NRS) were assessed. RESULTS: Decoctions of cannabis showed high variability in cannabinoids content, compared to cannabis oil. For both preparations, THCA-A and CBDA were the most widely absorbed cannabinoids, while THC and CBD were less absorbed. The most important differences concern the bioavailability of THC, higher in oil (AUC0-24 7.44, 95% CI 5.19, 9.68) than in decoction (AUC0-24 3.34, 95% CI 2.07, 4.60), and the bioavailability of CBDA. No serious adverse events were reported. CONCLUSIONS: Cannabis decoction and cannabis oil showed different pharmacokinetic properties, as well as distinct consequences on patients. This study was performed in a limited number of patients; future studies should be performed to investigate the clinical efficacy in larger populations.

Therapeutical approaches to paroxysmal hemicrania, hemicrania continua and short lasting unilateral neuralgiform headache attacks: a critical appraisal.

BACKGROUND: Hemicrania continua (HC), paroxysmal hemicrania (PH) and short lasting neuralgiform headache attacks (SUNCT and SUNA) are rare syndromes with a difficult therapeutic approach. The aim of this review is to summarize all articles dealing with treatments for HC, PH, SUNCT and SUNA, comparing them in terms of effectiveness and safety. METHODS: A survey was performed using the pubmed database for documents published from the 1st January 1989 onwards. All types of articles were considered, those ones dealing with symptomatic cases and non-English written ones were excluded. RESULTS: Indomethacin is the best treatment both for HC and PH. For the acute treatment of HC, piroxicam and celecoxib have shown good results, whilst for the prolonged treatment celecoxib, topiramate and gabapentin are good options besides indomethacin. For PH the best drug besides indomethacin is piroxicam, both for acute and prolonged treatment. For SUNCT and SUNA the most effective treatments are intravenous or subcutaneous lidocaine for the acute treatment of active phases and lamotrigine for the their prevention. Other effective therapeutic options are intravenous steroids for acute treatment and topiramate for prolonged treatment. Non-pharmacological techniques have shown good results in SUNCT and SUNA but, since they have been tried on a small number of patients, the reliability of their efficacy is poor and their safety profile mostly unknown. CONCLUSIONS: Besides a great number of treatments tried, HC, PH, SUNCT and SUNA management remains difficult, according with their unknown pathogenesis and their rarity, which strongly limits the studies upon these conditions. Further studies are needed to better define the treatment of choice for these conditions.

Onabotulinumtoxin A for the management of chronic migraine in current clinical practice: results of a survey of sixty-three Italian headache centers.

BACKGROUND: Chronic migraine is a complex clinical condition often undertreated. Onabotulinumtoxin A (OBT-A) was approved in Italy in 2013 for symptom relief in patients with chronic migraine who have failed, or do not tolerate, oral prophylactic treatments. However, the impact of OBT-A in clinical practice remains to be defined. METHODS: To investigate the current management of chronic migraine with OBT-A in clinical practice, a web-based survey was conducted among clinicians working in third-level headache centers across Italy. A 26-item questionnaire was designed and developed by a group of 10 Italian headache specialists to address the following issues: treatment paradigm and OBT-A injection intervals, frequency of treatment and retreatment, definition of responders/non-responders, satisfaction with treatment potential impact of early treatment with OBT-A. Ninety-six headache centers were selected and contacted via e-mail. The online survey was anonymous and carried out using a secure website. RESULTS: Overall, 64 of the 96 centers (66.7%) completed the questionnaire. Most centers (98.4%) had been using OBT-A for >1 year. OBT-A was administered according to the PREEMPT paradigm in most centers (88.9%). While during the first year of prophylaxis with OBT-A most clinicians (93.6%) repeated OBT-A treatment every 3 months, as recommended, in the following years interval duration was variable. Response to OBT-A was defined as a ≥ 50% reduction in the headache days by 58.7% of the clinicians, and as a ≥ 30% reduction by 25.4% of them. Almost 60% of the clinicians considered OBT-A as a long-lasting therapy, while for one-third of them treatment could be discontinued in patients showing a benefit for ≥6 months. According to 80% of the clinicians, early administration of OBT-A after the onset of chronic migraine was associated with better outcomes, and 47.6% felt that OBT-A should be recommended as a first-line option. CONCLUSIONS: This survey indicates that in third-level headache centers in Italy OBT-A is used in good compliance with current recommendations. There is agreement about the definition of response as a reduction in headache days by 30% to 50%. Additional effort is required to define response to OBT-A and to establish optimal treatment duration.

A genome-wide analysis in cluster headache points to neprilysin and PACAP receptor gene variants.

BACKGROUND: Cluster Headache (CH) is a severe primary headache, with a poorly understood pathophysiology. Complex genetic factors are likely to play a role in CH etiology; however, no confirmed gene associations have been identified. The aim of this study is to identify genetic variants influencing risk to CH and to explore the potential pathogenic mechanisms. METHODS: We have performed a genome-wide association study (GWAS) in a clinically well-defined cohort of 99 Italian patients with CH and in a control sample of 360 age-matched sigarette smoking healthy individuals, using the Infinium PsychArray (Illumina), which combines common highly-informative genome-wide tag SNPs and exonic SNPs. Genotype data were used to carry out a genome-wide single marker case-control association analysis using common SNPs, and a gene-based association analysis focussing on rare protein altering variants in 745 candidate genes with a putative role in CH. RESULTS: Although no single variant showed statistically significant association at the genome-wide threshold, we identified an interesting suggestive association (P = 9.1 × 10-6) with a common variant of the PACAP receptor gene (ADCYAP1R1). Furthermore, gene-based analysis provided significant evidence of association (P = 2.5 × 10-5) for a rare potentially damaging missense variant in the MME gene, encoding for the membrane metallo-endopeptidase neprilysin. CONCLUSIONS: Our study represents the first genome-wide association study of common SNPs and rare exonic variants influencing risk for CH. The most interesting results implicate ADCYAP1R1 and MME gene variants in CH susceptibility and point to a role for genes involved in pain processing. These findings provide new insights into the pathogenesis of CH that need further investigation and replication in larger CH samples.

Children's Headache: Drawings in the Diagnostic Work Up.

OBJECTIVES: This study aims to evaluate the drawings effectiveness in childhood headache assessment. BACKGROUND: Headache is a common cause of pain in children. Although drawings have been used in childhood to recognize psychological insights and pain perception, they were rarely used for headache characterization. METHODS: We collected drawings from 67 subjects with cephalalgia during a 22-month timeframe. The clinical diagnosis was made according to the 2nd edition of The International Headache Classification. Drawings were independently categorized as migraine or tension-type headache (TTH) by two child neuropsychiatrists blinded to the clinical data. Cohen kappa for interrater agreement, sensitivity, specificity, and positive predictive value (PPV) were calculated. Subjects were also divided into three age groups to assess the influence of age. Finally, a control group of 90 subjects was collected and K-means cluster analysis was performed. RESULTS: The drawings had a sensitivity of 85.71 and 81.48%, a specificity of 81.48 and 85.71%, and a PPV of 85.71 and 81.48%, for migraine and TTH diagnosis, respectively. Drawings by the older age group showed the highest predictability degree. Finally, by mean of cluster analysis, 59 of the 67 patients were correctly classified, whereas control subjects were similarly distributed between the two clusters. CONCLUSIONS: Drawings are a useful instrument for migraine and TTH differential diagnosis. Thus, we suggest their inclusion in childhood headache diagnostic assessment.

Increased efficacy of regularly repeated cycles with OnabotulinumtoxinA in MOH patients beyond the first year of treatment.

BACKGROUND: Chronic migraine is one of the most common diseases in the world and it is often associated with medication overuse that can worsen the headache itself. Thus, it is important to adopt effective therapies to relieve pain and improve patients' quality of life. The PREEMT studies have already demonstrated the effectiveness of OnabotulinumtoxinA in the treatment of chronic migraine. With this in mind, the aim of this real life observation has been to assess the clinical improvements as well as the impact on the quality of life of patients being regularly (every three months) administered this therapy. METHODS: Data from 66 chronic-migraineurs treated with OnabotulinumtoxinA after failing previous therapies were collected. Only 57 of them were analysed since 9 discontinued the therapy due to administrative reasons. For every patient enrolled, headache frequency, analgesic consumption, pain severity, headache-related disability, health-related quality of life as well as anxiety and depression symptoms were collected through the Headache Index (HI), analgesic consumption rate in one day (AC), VAS score, Headache Impact Test (HIT-6) and the Short Form (36) Health Survey questionnaire Version 2 (SF-36®), Zung Self-Rating Anxiety Scale (ZUNG-A) and Zung Self-Rating Depression Scale (ZUNG-D), respectively. All the changes vs baseline (Tx vs T0) were expressed as mean ± SD and analysed with a one-way ANOVA plus non-parametric Wilcoxon test, that was used for paired data for each subject. RESULTS: As the number of injection increased, those patients injected regularly observed a statistically significant reduction in the headache frequency, pain intensity, headache disability score and an overall marked improvement in patients' quality of life. There was also a significant reduction in anxiety and depressive symptoms as for the ZUNG-A and ZUNG-D scales scores. At any time point, those patients who stopped the therapy worsened their overall conditions as confirmed by quality of life parameters. CONCLUSIONS: This study outpoints that OnabotulinumtoxinA treatment is an effective treatment to reduce the headache-related disability and improve patients' quality of life when patients are treated regularly every three months and consistently overtime. Therapy discontinuation leads to a general worsening of health-related quality of life. Long term treatment over one year confirms a consistently positive and sustained trend of improvement with a high safety profile.

Validation of potential candidate biomarkers of drug-induced nephrotoxicity and allodynia in medication-overuse headache.

BACKGROUND: Medication-overuse headache (MOH) is a chronic disorder that results from the overuse of analgesics drugs, triptans or other acute headache compounds. Although the exact mechanisms underlying MOH remain still unknown, several studies suggest that it may be associated with development of "central sensitization", which may cause cutaneous allodynia (CA). Furthermore, the epidemiology of drug-induced disorders suggests that medication overuse could lead to nephrotoxicity. The aim of this work was to confirm and validate the results obtained from previous proteomics studies, in which we analyzed the urinary proteome of MOH patients in comparison with healthy non-abusers individuals. METHODS: MOH patients were divided into groups on the basis of the drug abused: triptans, non-steroidal anti-inflammatory drugs (NSAIDs) and mixtures, (mainly containing indomethacin, paracetamol and, in some cases, caffeine). Healthy subjects, with a history of normal renal function, were used as controls. In this study, four proteins that were found differentially expressed in urine, and, on the basis of the literature review, resulted related to kidney diseases, were verified by Western Blot and Enzyme-linked Immunosorbent Assay (ELISA); Prostaglandin-H2 D-synthase (PTGDS), uromodulin (UROM), alpha-1-microglobulin (AMBP) and cystatin-C (CYSC). RESULTS: Western blot analysis allowed to validate our previous proteomics data, confirming that all MOH patients groups show a significant over-excretion of urinary PTGDS, UROM, AMBP and CYSC (excluding triptans group for this latter), in comparison with controls. Moreover, the expression of PTGDS was further evaluated by ELISA. Also by this assay, a significant increase of PTGDS was observed in all MOH abusers, according to 2-DE and Western blot results. CONCLUSIONS: In this study, we confirmed previous findings concerning urinary proteins alterations in MOH patients, identified and demonstrated the over-expression of PTGDS, UROM, AMBP, and CYSC, particularly in NSAIDs and mixtures abusers. Over-expression of these proteins have been related to renal dysfunction and probably, PTGDS, to the development of CA. The detection and confirmation of this proteins pattern represent a promising tool for a better understanding of potential nephrotoxicity induced by drugs overuse and may enhance awareness related to the MOH-associated risks, even in absence of clinical symptoms.

The Nursing Role in the Management of Medication Overuse Headache: Realities and Prospects.

This review aims to analyze the current literature to identify articles related to the role of nurses and, in general, the nursing management of patients suffering from medication overuse headache (MOH), a globally spread disease. We specifically argue for non-pharmacological approaches to pain management, such as multidisciplinary team approaches, holistic treatment, cognitive behavioral therapy and exercise. For this review, we investigated international scientific databases, including PubMed, CINAHL, Scopus and Embase, in the period between 2000 and 2024. We observed a wealth of scientific articles related to MOH, but a poverty of articles relating to the nursing management of headache. The research included the presence of academic-level training for nurses, whereas there are few institutions that train competent professionals in both pharmacological and non-pharmacological management of MOH patients. Nursing assessment and assistance strategies are indicated to plan tailored treatment paths related to the specific needs of these patients.

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

BACKGROUND: Medication-overuse headache (MOH) is a chronic headache condition that results from the overuse of analgesics drugs, triptans, or other antimigraine compounds. The epidemiology of drug-induced disorders suggests that medication overuse could lead to nephrotoxicity, particularly in chronic patients. The aim of this work was to confirm and extend the results obtained from a previous study, in which we analyzed the urinary proteome of 3 MOH patients groups: non-steroidal anti-inflammatory drugs (NSAIDs), triptans and mixtures abusers, in comparison with non-abusers individuals (controls). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The omics in migraine.

The term omics consist of three main areas of molecular biology, such as genomics, proteomics and metabolomics. The omics synergism recognise migraine as an ideal study model, due to its multifactorial nature. In this review, the plainly research data featuring in this complex network are reported and analyzed, as single or multiple factor in pathophysiology of migraine. The future of migraine biomolecular research shall be focused on networking among these different and hierarchical disciplines. We have to look for its Ariadne's tread, in order to see the whole painting of migraine molecular biology.

Impact of continuing or quitting smoking on episodic cluster headache: a pilot survey.

BACKGROUND: The majority of patients suffering from cluster headache (CH) are smokers and it has been suggested that smoking may trigger the development of CH. The aim of this pilot survey was to describe: 1. the differences between current, former, and never smokers CH patients; 2. if smoking changed during an active cluster period; 3. if CH changed after quitting. METHODS: All outpatients with episodic CH according to the criteria of ICHD-II who were consecutively seen for the first time from October 2010 to April 2012 at a headache centre were interviewed by phone using a specifically prepared questionnaire. Statistical differences between continuous variables were analysed by the Student's t-test or the one-way analysis of variance (ANOVA), followed by Newman-Keuls post-hoc testing. Comparisons between percentages were made using the Chi-square test or Fisher's exact test. All data were expressed as the mean ± standard deviation (SD). RESULTS: Among a total of 200 patients surveyed (172 males, 28 females; mean age ± SD: 48.41 ± 12 years) there were 60%, 21%, and 19% of current, former, and never smokers, respectively. Current smokers reported longer active periods (12.38 ± 10 weeks) and a higher maximum number of attacks per day (3.38 ± 1) compared to never smoker CH patients (5.68 ± 4 weeks, P <0.05 and 2.47 ± 1, P <0.05, respectively). During the active period most of the patients stated to decrease (45.7%) or not to change (45.7%) the number of cigarettes smoked. Among those who decreased smoking, most (83.8%) reported that they had less desire to smoke. After quitting, the majority of former smokers stated that their headache had not changed. CONCLUSIONS: Patients with episodic CH who are also smokers appear to have a more severe form of the disorder. However, it is unlikely that between CH and smoking there is a causal relationship, as CH patients rarely improve quitting smoking.

Comparison of tolerability and efficacy of a combination of paracetamol + caffeine and sumatriptan in the treatment of migraine attack: a randomized, double-blind, double-dummy, cross-over study.

In this study, we compared the efficacy and tolerability of the combination of paracetamol 1,000 mg + caffeine 130 mg (PCF) with sumatriptan 50 mg (SUM) in migraine attacks. This was a multi-center randomized double-blind, double-dummy, cross-over controlled trial. The efficacy was assessed by the sum of pain intensity differences, the curve of mean pain intensity, the number of pain free at 2 h, and the total pain relief. Tolerability was assessed by recording adverse events within 4 h after drug assumption and evaluating the global judgement of patients. The comparison of these parameters did not show differences between the two drugs which resulted absolutely overlapping in pain relief and patients evaluation. In conclusion, we confirm the efficacy and safety of PCF such as SUM in the treatment of migraine attacks.