The different phases of an acute headache episode in chronic cluster patients were generally (6 out of 8 subjects) accompanied by rapid, significant changes in platelet-rich plasma (PRP) methionine-enkephalin (MET) levels. In contrast to these findings, platelet MET levels remained fairly unchanged in individual subjects and the observed intergroup variations well within the range of experimental error of the analytical technique used. With each patient serving as its own control we observed that “precluster” plasma peptide levels were substantially higher than their corresponding “during crisis” values, which in turn were higher than the “postcluster” MET concentration. When considered as a group, we showed statistically significant differences between the “pre” and “during cluster” and “pre” and “postcluster” headache phases, but not between the “during” and “postcluster” group of values. Each of these six patients had “precluster” PRP peptide concentration (range 198–318 pg MET/ml) above the range of normal controls (n=19, 54–126 pg MET/ml) and dramatically higher than their own levels when analyzed approximately six months later; at this time none of the subjects were in a “pro” or “during cluster” headache phase. In the other two patients PRP MET levels were fairly unchanged during the acute headache episode, at levels falling below the x ± 1 S.D. of normal controls.

These results show that, similarly to what has been reported for acute migraine headaches, the “precluster” phase of an acute cluster headache episode is accompanied by significant increases in plasma MET levels. However, and in contrast to migraine, peptide levels decrease rapidly to normal control values (“during cluster” phase), falling even further in the “postcluster” period. These results indicate that cluster patients lack the ability observed in migraineurs to keep a long lasting, sustained increase in plasma peptide concentration, a difference which could prove important for a better understanding of the possible different mechanisms involved in the modulation of the pain response between migraine and cluster headaches, as well as to differentiate biochemically both groups of patients.