Familial Hemiplegic Migraine Type 1 Shows no Hypersensitivity to Nitric Oxide

• Published in: Cephalalgia Vol. 28; no. 5; pp. 496 - 505
• Main Authors: Hansen, JM, Thomsen, LL, Olesen, J, Ashina, M
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.05.2008; Blackwell Publishing Ltd
• Subjects: Adult; Cyclic GMP - metabolism; Familial hemiplegic migraine; Female; Humans; Male; Middle Aged; migraine; migraine pathogenesis; Migraine with Aura - metabolism; neurotransmitters; nitric oxide; Nitric Oxide - metabolism; Nitroglycerin - administration & dosage; Signal Transduction - drug effects; Vasodilator Agents - administration & dosage; Familial hemiplegic migraine; nitric oxide; migraine; neurotransmitters; migraine pathogenesis
• ISSN: 0333-1024; 1468-2982
• DOI: 10.1111/j.1468-2982.2008.01559.x

Familial hemiplegic migraine type 1 (FHM-1) is a dominantly inherited subtype of migraine with aura and transient hemiplegia associated with mutations in the CACNA1A gene. FHM-1 shares many phenotypical similarities with common types of migraine, indicating common neurobiological pathways. Experimental studies have established that activation of the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway plays a crucial role in migraine pathophysiology. Therefore, we tested the hypothesis that CACNA1A mutations in patients with FHM-1 are associated with hypersensitivity to NO-cGMP pathway. We included eight FHM-1 patients with R583Q and C1369Y mutations and nine healthy controls, who received intravenous infusions of 0.5 μg kg−1 min−1 glyceryl trinitrate (GTN) over 20 min. We recorded: headache intensity on a verbal rating scale; mean flow velocity in the middle cerebral artery (VmeanMCA) by transcranial Doppler; diameter of the superficial temporal artery (STA) by Dermascan. One patient reported migraine without aura 5 h after start of the GTN infusion. No aura was reported. The AUCheadache in the immediate phase was more pronounced in patients than in controls (P = 0.01). In the 14 h following GTN infusion, there was no difference in the AUCheadache between patients and controls (P = 0.17). We found no difference in the AUCVmeanMCA (P = 0.12) or AUCSTA (P = 0.71) between FHM-1 patients and controls. None of the control persons reported migraine-like headache. FHM-1 patients do not show hypersensitivity of the NO-cGMP pathway, as characteristically seen in migraine patients with and without aura. This indicates that the pathophysiological pathways underlying migraine headache in FHM-1 may be different from the common types of migraine.