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 (po0.01 and po0.02, respectively). A negative correlation was found between AEA and CGRP levels in CM and PCM + PAOH patients (r ¼ 0.59, po0.01 and r ¼ À0.65, po0.007; 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.

Dependent Behavior in Patients with Medication-Overuse Headache

“…In support of this hypothesis, Sarchielli and colleagues [41] found cerebrospinal fluid (CSF) concentrations of anandamide (AEA), a biologically active endocannabinoid, were lower in patients with chronic migraine with or without MOH than in nonmigraine control patients [41]. They further demonstrated the platelet levels of AEA and 2-acylglycerol, another biologically active endocannabinoid, were lower in patients with chronic migraine with and without MOH than in control patients, and serotonin levels also were reduced in these two CDH patient groups, with higher values for the MOH patients [42].…”

Migraine and neuropeptides

“…In female migraineurs during NTG-induced migraine attacks the plasma CGRP concentration proved to be decreased in parallel with the headache intensity score after the administration of sumatriptan (Juhasz et al, 2005). An increased CGRP level has been reported in the cerebral spinal fluid (CSF) in chronic migraine subjects as compared with control subjects (Sarchielli et al, 2007). Intravenous administration of CGRP caused migraine-like attacks both in migraineurs with aura and in those without aura (Hansen et al, 2010;Lassen et al, 2002).…”

Medical marijuana in neurology

“…Experimental evidence suggests there are reduced levels of AEA in the cerebrospinal fluid of patients with chronic migraine and analgesic overuse headache. These results suggest that impairment of the endogenous cannabinoid system may result in increased calcitonin gene-related peptide and no production, allowing for activation of the trigeminovascular system, subsequent sensitization and potential for 'chronification' of pain [25]. Evidence suggests that there is increased degradation of AEA in platelets of female (but not male) migraineurs, suggesting that the decreased level of circulating AEA may contribute to a reduced pain threshold [26].…”