Pulse pressure obtained from alternatively calibrated tonometer-derived pressure waves and echo-tracking-derived distension waves demonstrates good accuracy. Accuracy of pulse pressure from internally calibrated applanation tonometer readings at the carotid artery is poor.

Functional arterial properties are altered in patients with migraine of recent onset.

Our study demonstrates that the innate pressure-dependence of arterial stiffness may have implications for the clinical use of arterial stiffness measurements, both in risk assessment and in treatment monitoring of individual patients. We propose a number of clinically feasible approaches to account for the blood pressure effect on PWV measurements.

Interictal serum C-reactive protein (CRP) was measured in 50 young adult patients with migraine and compared with 50 controls. The median CRP level was 1.42 mg/l in patients with migraine and 0.90 mg/l in controls (P = 0.03). This finding supports the role of inflammation in migraine, but needs confirmation in larger controlled studies. Prospective studies may establish whether measurements of CRP can identify patients with migraine at risk for cardiovascular events.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Calcitonin gene-related peptide (CGRP) was first described as a potent vasodilator.• CGRP is also increasingly recognized as a key player in the pathophysiology of migraine, and CGRP receptor antagonists potentially offer a new approach for treating migraine.• A novel pharmacodynamic assay to measure CGRP receptor antagonist activity non-invasively in humans has been developed, which involves measuring the increase in dermal blood flow induced by topical application of capsaicin on the forearm. WHAT THIS STUDY ADDS• This study shows that the novel oral CGRP receptor antagonist, telcagepant, inhibits the increases in dermal blood flow induced by the topical application of capsaicin on the human forearm.• This experimental medicine model may have utility to assist in dose selection for the development of CGRP receptor antagonists. AIMSTo evaluate inhibition of capsaicin-induced increase in dermal blood flow (DBF) following telcagepant (MK-0974), a potent and selective orally bioavailable calcitonin gene-related peptide (CGRP) receptor antagonist being developed for the acute treatment of migraine. METHODSA three-period crossover study in 12 healthy adult men. Each subject received a single oral dose of telcagepant 300 mg, telcagepant 800 mg or placebo at 0 h, followed 0.5 and 3.5 h later by two topical doses of 300 and 1000 mg capsaicin per 20 ml water-ethanol mixture. Capsaicin was applied at two sites on the volar surface of the subjects' left and right forearms. DBF was assessed by laser Doppler perfusion imaging immediately before ('baseline'), and 0.5 h after each capsaicin application at 1 and 4 h. Plasma samples to determine telcagepant concentrations were collected immediately after laser Doppler perfusion imaging. A pharmacodynamic model was developed to explore the relationship between plasma concentration and inhibition of capsaicininduced increase in DBF. RESULTSGeometric mean plasma concentrations after dosing with 300 mg and 800 mg telcagepant were 720 and 1146 nM, respectively, at 1 h, vs. 582 and 2548 nM, respectively, at 4 h. The pharmacodynamic model suggested that the EC90 for telcagepant inhibition of capsaicin-induced increases in DBF was 909 nM. CONCLUSIONSTelcagepant inhibits the increases in DBF induced by the topical application of capsaicin on the human forearm. This experimental medicine model may have utility to assist in dose selection for the development of CGRP receptor antagonists.