PIII‐36

BACKGROUND Administration of nitric oxide (NO) donors provides a reliable model of migraine induction. NO was reported to cause a reproducible dilation of meningeal vessels and delayed inflammation in rat meninges. This may contribute to the pathogenesis of migraine headaches. TPM, an anti‐seizure drug, has shown efficacy in migraine prophylaxis, however, the mechanism of this effect is unclear. We studied the effect of GTN infusion on DBF in migraineurs before and after an 8‐week course of TPM. METHODS Migraineurs with and without aura (IHS criteria) underwent measurement of DBF using 15 O‐water (H 2 15 O) and positron emission tomography (PET). Measurements were made at baseline and following stepwise infusion of GTN at 0.125, 0.25 and 0.5 mcg/kg/min (∼15 min at each dose step), and were repeated following 8w of treatment with a maximal dose of 100mg BID of TPM. Quantitative measurement of blood flow was done in a series of regions of interest (ROI) including an ROI inclusive of the dura mater. RESULTS The following table shows DBF (mL/min/g) measurements obtained from 8 migraineurs; mean (SD). ANOVA demonstrated no statistically significant interaction between TPM and GTN (p>0.05).Baseline 0.125 * 0.25 * 0.5 * 30 min post * 60 min post *Pre TPM 0.44 (0.1) 0.47 (0.1) 0.48 (0.2) 0.44 (0.1) 0.47 (0.1) 0.44 (0.1)Post TPM 0.77 (0.6) 0.60 (0.2) 0.51 (0.1) 0.52 (0.2) 0.52 (0.2) 0.47 (0.1)GTN (mcg/kg/min).CONCLUSIONS Migraineurs, on or off TPM, did not show a significant change in their DBF during and shortly after GTN infusion. Delayed measurements of regional cerebral blood flow at different ROIs including the dura mater may reveal a possible involvement of human meninges in migraine pathogenesis. Clinical Pharmacology & Therapeutics (2005) 79 , P68–P68; doi: 10.1016/j.clpt.2005.12.244