The effect of adrenergic compounds on neurogenic dural vasodilatation

The pharmacology of neurogenic trigeminovascular vasodilator responses in t he dura mater is of interest for understanding the pathophysiology of migra ine and to develop new therapies for this disabling common condition. Amine rgic mechanisms have been implicated in migraine through direct study of am ines in patients, and by inference from the pharmacology of many effective anti-migraine compounds, particularly preventative agents. This study used intravital microscopy to assess the role of aminergic transmission in neuro genic dural vasodilatation (NDV) by measuring directly the diameter of dura l arteries in sodium pentobarbitone anaesthetised rats. Electrical stimulat ion of a closed cranial window produces, by local depolarisation of nerves, dural vessel dilation that is monitored continuously on-line using video-m icroscopy and a video dimension analyser. This dural vasodilatation was not affected by pre-treatment with an alpha (1)-adrenoceptor agonist (phenylep hrine, 1 and 5 mug/kg), or antagonist (corynanthine, 1 and 2 mg/kg), nor by an alpha (2)-adrenoceptor agonist (UK14,304, 5 mug/kg) or antagonist (yohi mbine, 1 and 3 mg/kg). Similarly, we saw no effect of beta -adrenoceptor bl ockade (propranolol, 1 and 3 mg/kg). The lack of an inhibitory effect of UK 14,304 the model of neurogenic dural vasodilation contrasts with its effect in neurogenic dural plasma protein extravasation model. The lack of inhibi tion of beta -adrenoceptor antagonists in the neurogenic vasodilatation mod el contrasts with their usefulness as migraine prophylactics, and suggests that their mechanism of action in migraine is unlikely to be through sensor y trigeminal fibre terminals at the neurovascular junction. Moreover, the d ata indicate that the adrenergic system does not play a significant role in neurogenic dural vasodilation. (C) 2001 Elsevier Science B.V. All rights r eserved.