Drug consumption in medication overuse headache is

Authors: Cherubino Di Lorenzo Giorgio Di Lorenzo Grazia Sances Natascia Ghiotto Elena Guaschino Gaetano S Grieco Filippo M Santorelli Carlo Casali Alfonso Troisi Alberto Siracusano Francesco Pierelli

Publish Date: 2009/10

Volume: 10, Issue: 5, Pages: 349-

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Abstract

Medication overuse headache MOH can be considered a clinical condition at the boundaries between drug addiction and chronic pain disorder The common 196G  A singlenucleotide polymorphism of BDNF gene resulting in a valine 66 to methionine Val66Met is related with behaviour disorders and substance abuse With the aim of identifying a worsening factor in MOH rather than the detection of a specific risk factor for the development of the disease we investigated whether the presence of a functional BDNF polymorphism might determine clinical differences within a group of 90 MOH patients particularly in monthly drug consumption that is the hallmark of disease Directly comparing MOH patients homozygous for G allele G/G with carriers of A allele nonG/G we have observed 47 G/G genotypes and 60 nonG/G genotypes NonG/G had a higher consumption of monthly drug number Cohen’s d = 076 than G/G patients At multiple regression analysis the Val66Met BDNF polymorphism emerged as a significant independent predictor of analgesic drug consumption Beta = 033 Cohen’s f2 = 0134 These findings showed an influence of examined BDNF polymorphism in the MOH clinical features supporting the idea that MOH is a substance abuse disorderMedication overuse headache MOH is a chronic headache disorder due to overuse of analgesic medicines taken to treat a primary headache and remitted by drug discontinuation 1 MOH has long been considered as a “biobehavioural” disorder in which the biological predisposition to develop a chronic headache interacts with an individual behaviour prone to develop a dependence disorder 2 3 The molecular basis of MOH are largely unknown though it has been hypothesized that this subtype of headache could be mediated by cognitive impulsivity and shares some pathophysiological mechanisms with drug addiction including dysfunction of the frontostriatal system and central pain sensitization induced by drug overuse 4 Based on this hypothesis there seems to be a role in MOH for BDNF brainderived neurotrophic factor because of its role in central pain sensitization and its relationship with substancerelated disorders 5 6BDNF is a member of “neurotrophin” family a unique group of polypeptide growth factors that influence differentiation and survival of neurons in the developing nervous system BDNF is involved in longterm potentiation LTP and therefore in learning and memory mechanisms Also a pathogenic role for BDNF has been shown in pain transduction and sensitization in epilepsy and in neuropsychiatric disorders 5BDNF is a member of “neurotrophin” family a unique group of polypeptide growth factors that influence differentiation and survival of neurons in the developing nervous system BDNF is involved in longterm potentiation LTP and therefore in learning and memory mechanisms Also a pathogenic role for BDNF has been shown in pain transduction and sensitization in epilepsy and in neuropsychiatric disorders 5BDNF gene mapped to chromosome 11p encodes for proBDNF that is subsequently cleaved in its mature form 5 Recently it has been observed that a common 196G  A singlenucleotide polymorphism SNP of BDNF gene resulting in a valine at residue 66 to methionine Val66Met substitution in proBDNF protein exhibits a functional relevance in that it seems to reduce BDNF activity by altering neurotrophin trafficking 7 The Val66Met variant affects anatomy cognition and behaviour in adults 7 and leads to memory impairment 5 and susceptibility to obsessivecompulsive eating substance abuse and mood disorders 6 8–10The rationale behind our study derives from two findings which have been consistently reported in previous researches 1 overuse of analgesic drugs is a defining feature of MOH and for this reason MOH has been related to behavioural syndromes associated with substance abuse 1–3 2 there is evidence that proneness to use/abuse substances is associated with the allele A of BDNF polymorphism 6Therefore we tested the frequency of the Val66Met genotype in a sample of MOH patients and compared clinical features between individuals homozygous for G allele G/G and carriers of the allele A nonG/G Aim of this study is to confirm our hypothesis that allele A of the examined BDNF polymorphism interfere with MOH seeking for clinical and psychiatric differences between the two groups mainly in the monthly drug consumption that is both the clinical hallmark of disease and the feature closest to abuse disorderWe would like to emphasize that although such studies are necessary to get a deeper understanding of the association between MOH and BDNF polymorphism the present study did not intend to ascertain whether the BDNF polymorphism is a risk factor for the development of MOH but only an aggravating factor for subjects that have already developed the disorderUnrelated consecutive MOH patients were enrolled from two Italian University Headache Clinics the inpatient HeadacheUnit of IRCCS “C Mondino” Institute of Neurology Foundation Pavia and Headache Outpatient Department of University of Rome “La Sapienza” among those admitted with a diagnosis of probable MOH 1 to undergo withdrawal from their overused medications Although revised criteria were formulated for MOH 11 patients’ enrolment was started before their statement thus original ICHDII version ie in the presence of headache improvement within 2 months after analgesics withdrawal 1 that is more conservative was adopted to recruit all patients a retrospective analysis will also confirm that all enrolled patients fulfilled the revised criteria

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