Methionine-enkephalin and serotonin in migraine and tension headache

Neuronal Signal Substances as Biomarkers of Migraine

“…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.…”

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.…”

Neuropeptides in Migraine and Cluster Headache

“…Morphine-like substances have been reported to be reduced during migraine (52), although no change in ß-endorphin can be detected (53). Interestingly, plasma and platelet met-enkephalin levels are moderately increased during headache (54,55).…”

“…Again, as with simple migraine with aura, plasma vasopressin levels are unchanged during headache (49). Conflicting data have emerged concerning the opioids; in two studies met-enkephalin and ß-endorphin have been shown to be marginally elevated (54,55), while in other studies no change has been found specifically in ß-endorphin (53). Studies of the cerebrospinal fluid have been limited to demonstrating that there is no change in either SP or somatostatin during headache (58).…”