A systematic review and critical appraisal of gene polymorphism association studies in medication-overuse headache

Abstract

Purpose of review Medication-overuse headache is a secondary chronic headache disorder, evolving from an episodic primary headache type, caused by the frequent and excessive use of headache symptomatic drugs. While gene polymorphisms have been deeply investigated as susceptibility factors for migraine, little attention has been paid to medication-overuse headache genetics. In the present study we conducted a systematic review to identify, appraise and summarize the current findings of gene polymorphism association studies in medication-overuse headache. Methods A comprehensive literature search was conducted on PubMed and Web of Knowledge databases of primary studies that met the diagnostic criteria for medication-overuse headache according to the temporally-relevant Classification of Headache Disorder of the International Headache Society. Results A total of 17 candidate gene association studies focusing on medication-overuse headache were finally included in the qualitative review. Among these, 12 studies investigated the role of common gene polymorphisms as risk factors for medication-overuse headache susceptibility, six studies focused on the relationship with clinical features of medication-overuse headache patients, and four studies evaluated their role as determinants of clinical outcomes in medication-overuse headache patients. Conclusion Results of single studies show a potential role of polymorphic variants of the dopaminergic gene system or of other genes related to drug-dependence pathways as susceptibility factors for disease or as determinants of monthly drug consumption, respectively. In this systematic review, we summarize the findings of gene polymorphism association studies in medication-overuse headache and discuss the methodological issues that need to be addressed in the design of future studies.

Medication-overuse headache: a widely recognized entity amidst ongoing debate

“…In a recent systematic review, Cargnin et al described candidate polymorphic variants in genes of the dopaminergic gene system (DRD4, DRD2, SLC6A3), and genes related to drug-dependence pathways (WSF1, BDNF, ACE, HDAC3). The authors concluded that these traits are potential risk factors for MOH susceptibility or determinants of monthly drug consumption [ 100 – 107 ].…”

The Many Faces of Medication‐Overuse Headache in Clinical Practice

“…The development of MOH is associated with a background of a primary headache disorder, frequent intake of analgesics, increasing frequency of headaches, psychological and personality traits, and genetic predisposition 24,25 . Genes involved in pain, drug‐dependence, metabolic, serotonergic, and dopaminergic pathways have been linked to MOH 24‐28 . Interestingly, regular use of analgesics for a non‐headache indication is associated with the development of chronic headache, specifically in migraine patients 29,30 .…”

Evaluation of LY573144 (lasmiditan) in a preclinical model of medication overuse headache

“…Imaging studies, however, indicate differences in the brains of patients with migraine and with MOH, including reductions in the grey matter volume in areas associated with pain processing ( 41 , 42 ), and functional reactivity and resting state connectivity of brain regions involved in pain processing and modulation as well as cognitive and affective processing of pain ( 43 ). Furthermore, genetic studies have suggested particular gene polymorphisms may increase the risk of patients developing MOH, including genes involved in dopaminergic and serotonergic pathways ( 44 ). These studies augment findings that the serotonin (5-HT) system is altered in MOH, with decreased 5-HT levels ( 45 ) and increased levels of 5-HT receptors ( 46 ) in patients with MOH.…”