Endocannabinoids in Chronic Migraine: CSF Findings Suggest a System Failure

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 32; no. 6; pp. 1384 - 1390
• Main Authors: Sarchielli, Paola, Pini, Luigi Alberto, Coppola, Francesca, Rossi, Cristiana, Baldi, Antonio, Mancini, Maria Luisa, Calabresi, Paolo
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2007; Nature Publishing; Nature Publishing Group
• Subjects: Adult; Analgesics; Arachidonic Acids - cerebrospinal fluid; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Calcitonin Gene-Related Peptide - cerebrospinal fluid; Cannabinoid Receptor Modulators - cerebrospinal fluid; Chromatography; Chromatography, High Pressure Liquid; Chronic Disease; Dopamine; Endocannabinoids; Ethanolamines; Female; Fibromyalgia; Gas Chromatography-Mass Spectrometry; Glycerides - cerebrospinal fluid; Headache Disorders, Secondary - cerebrospinal fluid; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Headaches; Humans; Irritable bowel syndrome; Male; Medical sciences; Medicine; Medicine & Public Health; Migraine; Migraine Disorders - cerebrospinal fluid; Nervous system (semeiology, syndromes); Neurology; Neurosciences; Nitric oxide; Nitrites - cerebrospinal fluid; original-article; Palmitic Acids - cerebrospinal fluid; Peptides; Pharmacotherapy; Polyunsaturated Alkamides - cerebrospinal fluid; Psychiatry; Public health; Surveys and Questionnaires; Vascular diseases and vascular malformations of the nervous system; Italy; analgesic overuse headache; calcitonin gene-related peptide; endocannabinoids; nitrites; chronic migraine; cerebrospinal fluid; Headache; Nervous system diseases; Migraine; Nitrites; Cardiovascular disease; Endogenous substance; Calcitonin gene related peptide; Cerebrospinal fluid; Cannabinoid; Neuropeptide; Cerebral disorder; Vascular disease; Chronic; Analgesic; Pain; Endocannabinoid; Central nervous system disease; Drug of abuse; Neurological disorder; Cerebrovascular disease
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/sj.npp.1301246

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.