Plasma Methionine Enkephalin. Increased Levels During a Migraine Episode

Abstract

SYNOPSIS Plasma methionine‐enkephalin (MET) levels in migraine patients, either during an attack or when pain‐free, are statistically significantly higher than in matched controls; this is also true when comparing the classical and nonclassical migraine subpopulations with the control group. Individual patients consistently presented lower MET plasma concentrations in the pain‐free period than during the acute headache, with some subjects showing values falling within the range of controls. Platelet neuropeptide content was similar in patients and controls, irrespective of plasma MET levels. These results indicate that increased plasma MET concentrations are associated with the occurrence of a migraine episode and suggests that they are not a constant characteristic of migraineurs.

Neuronal Signal Substances as Biomarkers of Migraine

“…During attacks of cluster headache, somatostatin and substance P levels are not changed or at most slightly reduced 15 . On the other hand a more consistent pattern of reactivity has been noted for Met‐enkephalin and β‐endorphin, both showing increased plasma levels in migraine 6,16 …”

“…There have been many studies of plasma levels of Met‐enkephalin and β‐endorphin. In general there appears to be a slight increase in Met‐enkephalin in migraine 5–7 . One interesting observation is that the Met‐enkephalin levels are almost 10 times higher outside attacks than during headache attacks and in control patients.…”

“…Several studies reported on decreased CSF levels of “morphine”‐like factors and changes in plasma β‐endorphin levels in unspecified headache sufferers 13 . However, there are studies on platelet and plasma levels of Met‐enkephalin that show that they are increased, albeit only slightly, in patients with migraine 5–7 . Another study on 11 patients with migraine 8 did not reveal any change in plasma levels of β‐endorphin and ACTH in headache attacks as compared to headache‐free periods.…”

Role of neuropeptides in migraine: where do they stand in the latest expert recommendations in migraine treatment?

“…Met-Enk-containing neurons and terminals are present in the mesencephalon and spinal cord, and Met-Enk may be released from such terminals on somatic stimulation [Yaksh and Elde, 1981]. Increased levels of Met-Enk [Mosnaim et al, 1985[Mosnaim et al, , 1986 and b-endorphin levels have been detected in the plasma of migraine patients [see Edvinsson, 2006, for review].…”

Selected Confirmed, Probable, and Exploratory Migraine Biomarkers

“…Twenty‐two different mutations identified.SCN1A mutations on chromosome 2q24Familial hemiplegic migraine 3Genetic linkage studies; mutational analysisTrait (genetic marker) 26 Encodes α1 subunit of neuronal voltage‐gated sodium channel.C677T mutations in methylenetetrahydrofolate reductase (MHTR) geneMigraine without aura in clinic and population‐based studiesAssociation studiesTrait (genetic marker) 27–31 Homozygosity for C677T variant confers 2× increase in risk for migraine with aura; effect increased in combination with ACE ID/DD genotype. ACE‐DD variant seemed to have a slight protective effect against migraine in male patients.Short/short genotype of 5‐HTTLPR on serotonin transporter geneMigraine with and without auraAssociation studiesTrait (genetic marker) 32–38 Risk factor for increased attack frequency, especially in patients with migraine with aura.4q21‐24Migraine with and without auraGenetic linkage studiesTrait (genetic marker) 39,40 Identified in Finnish families (migraine with aura); overlaps with allele identified in Icelandic study (migraine without aura).6p12.2‐p21.1Migraine with and without auraGenetic linkage studies; latent class analysisTrait (genetic marker) 41,42 Identified in Swedish families; supported by an Australian study.Altered levels of met‐enkephalinMigrainePlasma and platelet assaysTrait (interictal) and state (during headache) 41–44 Met‐enkephalin levels almost 10× higher outside attacks than during attacks or in control subjects. During migraine attacks both platelet and plasma concentrations increase; between attacks they had high platelet and reduced plasma levels.Increased CGRP levels in external jugular veinMigrainePlasma assayState (during headache) 45,46 No change in levels of neuropeptide Y, vasoactive intestinal polypeptide, or Substance P. CGRP plasma levels return to normal upon headache relief with sumatriptan.…”