Experimental studies have shown that infusion of vasoactive neurotransmitters may trigger headache or migraine-like attacks in man. Pituitary adenylate cyclase activating peptide-38 (PACAP38) is a strong vasodilator found in trigeminal sensory and parasympathetic perivascular nerve fibers. We therefore hypothesized that infusion of PACAP38 would cause headache in healthy subjects and migraine-like attacks in migraine patients. Twelve healthy subjects and 12 migraine patients were examined in two separate studies. All subjects were allocated to receive 10 pmol/kg/min PACAP38 and placebo in a randomized, double-blind crossover study design. Headache was scored on a verbal rating scale (VRS) during hospital (0-2 h) and post-hospital (2-12 h) phases. Mean blood flow velocity in the middle cerebral artery (V(MCA)) by transcranial Doppler (TCD) and diameter of the superficial temporal artery (STA) by high resolution ultrasonography were recorded during hospital phase in migraineurs. PACAP38 infusion caused headache in all healthy subjects and 11 out of 12 migraine patients. Seven migraine patients experienced migraine-like attacks after PACAP38 and none after placebo (P = 0.016). Most of attacks (6 out of 7) occurred during the post-hospital phase [mean time 6 h (range 2-11)]. Two healthy subjects reported migraine-like attacks after PACAP38 during the hospital phase and none during the post-hospital phase. In the hospital phase, the area under the curve (AUC) for headache score was larger during PACAP38 infusion compared to placebo in healthy subjects (P = 0.005) and tended to be larger in migraineurs (P = 0.066). In the post-hospital phase, the AUC for headache was larger after PACAP38 infusion compared to placebo in both healthy subjects (P = 0.005) and migraine patients (P = 0.013). In migraine patients, PACAP38 caused a peak decrease of 16.1% in V(MCA) and a 37.5% increase in STA diameter at 20 min after start of infusion. In conclusion, PACAP38 infusion caused headache and vasodilatation in both healthy subjects and migraine patients. In migraine sufferers, PACAP38 caused delayed migraine-like attacks. The findings stimulate further investigation of the neuronal and vascular mechanisms of PACAP38.
Background: Prostaglandin E2 (PGE2) has been suggested to play an important role in the pathogenesis of migraine. In the present experiment we investigated if an intravenous infusion of PGE2 would induce migraine-like attacks in patients with migraine. Methods: Twelve patients with migraine without aura were randomly allocated to receive 0.4 µg/kg/min PGE2 (Prostin®E2, dinoprostone) or placebo over 25 minutes in a two-way, crossover study. Headache intensity was recorded on a verbal rating scale, middle cerebral artery blood flow velocity (VMCA) was measured by transcranial Doppler (TCD) and diameter of the superficial temporal artery (STA) was obtained by c-series scan (Dermascan C). Results: In total, nine migraine patients (75%) experienced migraine-like attacks after PGE2 compared to none after placebo (p = 0.004). Seven out of 9 (58%) patients reported the migraine-like attacks during the immediate phase (0–90 min) (p = 0.016). Only two patients experienced the delayed migraine-like attacks several hours after the PGE2 infusion stop (p = 0.500). The VMCA decreased during the PGE2 infusion (p = 0.005) but there was no significant dilatation of the STA (p = 0.850). Conclusion: The migraine-like attacks during, and immediately after, the PGE2 infusion contrast with those found in previous provocation studies, in which the other pharmacological compounds triggered the delayed migraine-like attacks several hours after the infusion. We suggest that PGE2 may be one of the important final products involved in the generation of migraine attacks.
Measurements of cerebral blood flow (CBF) show large variability among healthy subjects. The aim of the present study was to investigate the relative effect of established factors influencing CBF on the variability of resting CBF. We retrospectively analyzed spontaneous variability in 430 CBF measurements acquired in 152 healthy, young subjects using 133 Xe single-photon emission computed tomography. Cerebral blood flow was correlated positively with both end-tidal expiratory P CO 2 (P ET CO 2 ) and female gender and inversely with hematocrit (Hct). Between-and within-subject CO 2 reactivity was not significantly different. Including P ET CO 2 , Hct and gender in the model reduced between-subject and within-subject variance by 14% and 13.5%, respectively. Withinsubject variability was mainly influenced by P ET CO 2 and between-subject variability mostly by Hct, whereas gender appeared to be of little added value when Hct was also accounted for. The present study confirms large between-subject variability in CBF measurements and that gender, Hct, and P ET CO 2 explain only a small part of this variability. This implies that a large fraction of CBF variability may be due to unknown factors such as differences in neuron density or metabolism that could be subject for further studies.
Background and purpose-It is important to find a reliable and bedside method, which can estimate the cerebral blood flow (CBF) of patients in clinical settings. Estimation of CBF by calculating a blood flow index (BFI) using continuous wave near-infrared spectroscopy (CW-NIRS) and indocyanine green (ICG) as an iv tracer has been proposed to be a feasible and promising method. To validate if the BFI method can detect relative changes in CBF we compared data with the established method 133 Xenon single photon emission computer tomography ( 133 Xe-SPECT).
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