title: Endocannabinoids in chronic migraine: CSF findings suggest a system failure.
abstract: Based on experimental evidence of the antinociceptive action of endocannabinoids and their role in the modulation of trigeminovascular system activation, we hypothesized that the endocannabinoid system may be dysfunctional in chronic migraine (CM). We examined whether the concentrations of N-arachidonoylethanolamide (anandamide, AEA), palmitoylethanolamide (PEA), and 2-arachidonoylglycerol (2-AG) in the CSF of patients with CM and with probable CM and probable analgesic-overuse headache (PCM+PAOH) are altered compared with control subjects. The above endocannabinoids were measured by high-performance liquid chromatography (HPLC), and quantified by isotope dilution gas-chromatography/mass-spectrometry. Calcitonin gene-related peptide (CGRP) levels were also determined by RIA method and the end products of nitric oxide (NO), the nitrites, by HPLC. CSF concentrations of AEA were significantly lower and those of PEA slightly but significantly higher both in patients with CM and PCM+PAOH than in nonmigraineur controls (p<0.01 and p<0.02, respectively). A negative correlation was found between AEA and CGRP levels in CM and PCM+PAOH patients (r=0.59, p<0.01 and r=-0.65, p<0.007; respectively). A similar trend was observed between this endocannabinoid and nitrite levels. Reduced levels of AEA in the CSF of CM and PCM+PAOH patients may reflect an impairment of the endocannabinoid system in these patients, which may contribute to chronic head pain and seem to be related to increased CGRP and NO production. These findings support the potential role of the cannabinoid (CB)1 receptor as a possible therapeutic target in CM.
authors.affiliation: Neurologic Clinic, Department of Medical and Surgical Specialties and Public Health, University of Perugia, Perugia, Italy. neuro.pg@tiscalinet.it
authors.forename: Paola
authors.initials: P
authors.lastname: Sarchielli
authors.forename: Luigi Alberto
authors.initials: LA
authors.lastname: Pini
authors.forename: Francesca
authors.initials: F
authors.lastname: Coppola
authors.forename: Cristiana
authors.initials: C
authors.lastname: Rossi
authors.forename: Antonio
authors.initials: A
authors.lastname: Baldi
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mancini
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
mesh_terms: D000328:Adult; D000577:Amides; D001095:Arachidonic Acids / Q000134:cerebrospinal fluid; D015740:Calcitonin Gene-Related Peptide / Q000134:cerebrospinal fluid; D063385:Cannabinoid Receptor Modulators / Q000134:cerebrospinal fluid*; D002851:Chromatography, High Pressure Liquid; D002908:Chronic Disease; D063388:Endocannabinoids; D004983:Ethanolamines; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005989:Glycerides / Q000134:cerebrospinal fluid; D051271:Headache Disorders, Secondary / Q000134:cerebrospinal fluid; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000134:cerebrospinal fluid*; D009573:Nitrites / Q000134:cerebrospinal fluid; D010169:Palmitic Acids / Q000134:cerebrospinal fluid; D053284:Polyunsaturated Alkamides / Q000134:cerebrospinal fluid; D011795:Surveys and Questionnaires
chemical_list: D000577:Amides; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D004983:Ethanolamines; D005989:Glycerides; D009573:Nitrites; D010169:Palmitic Acids; D053284:Polyunsaturated Alkamides; C005958:palmidrol; C094503:glyceryl 2-arachidonate; D015740:Calcitonin Gene-Related Peptide; C078814:anandamide