Increased Plasma Matrix Metalloproteinase-9 Levels in Migraineurs


  • Conflict of Interest: None.

Dr. Takao Takeshima, Associate Professor of Neurology, Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36-1 Nishicho, Yonago, 683-8504, Japan.


Background and Objective.— Cortical spreading depression and neurogenic inflammation have been hypothesized to be key steps in the development of migraine headache. Recent studies have highlighted matrix metalloproteinase-9 (MMP-9) in cortical spreading depression, neurogenic inflammation, and cerebral ischemia. To seek their possible association, we investigated plasma MMP-9 levels in migraineurs during headache-free periods.

Methods.— Plasma MMP-9 levels in 84 migraine subjects and 61 controls were determined by enzyme-linked immunosorbent assay. In addition, 23 patients with tension type headache were included in the study as comparative subjects.

Results.— The MMP-9 levels in migraineurs (42.5 ± 4.6 ng/mL, mean ± SE) were significantly higher than those in controls (25.4 ± 2.7 ng/mL, P < .005). Those levels in tension type headache subjects (24.6 ± 4.8 ng/mL) did not differ from those in controls. There was no significant difference between subjects having migraine with aura and those without aura. The MMP-9 levels did not correlate with age, duration of illness, frequency of migraine attack, duration of headache attack, or medication for headache. Mean plasma MMP-9 levels were the highest in subjects from whom blood samples were taken 2-4 days after their latest attack.

Conclusions.— The degradation of extracellular matrix showing the increase of MMP-9 in migrainurs may be associated with an abnormality in their blood vessel permeability. MPP-9 plays some role in migraine pathophysiology. Further studies of MMPs are necessary to elucidate their role.