Role of opioid receptors in neurogenic dural vasodilation and sensitization of trigeminal neurones in anaesthetized rats

1 Migraine headache is thought to be caused by a distension of meningeal bl ood vessels, the activation of trigeminal sensory neurones and the the deve lopment of a central sensitization within the trigeminal nucleus caudalis ( TNC). It has been proposed that clinically effective 5-HT1B/1D agonists act peripherally to inhibit the release of calcitonin gene-related peptide (CG RP) and neurogenic dural vasodilation, and to attenuate nociceptive neurotr ansmission within the TNC. Since opioids are also effective anti-migraine a gents the present studies investigated the role of opioids within the trige mino-vascular system in anaesthetised rats. 2 Electrical stimulation of the dura mater evoked neurogenic dural vasodila tion which was significantly inhibited by morphine (1 mg kg(-1)) the select ive mu -opioid agonist DAGO (10 mug kg(-1)) and the mixed agonist/antagonis t butorphanol (1 mg kg(-1)) but not by the kappa- and delta -opioid agonist s (+/-) U50488H (100 mug kg(-1)) and DPDPE (1 mg kg(-1)). Morphine had no e ffect on CGRP-evoked dural vasodilation. 3 In electrophysiological studies morphine (1-10 mg kg(-1)) significantly a ttenuated brainstem neuronal activity in response to electrical stimulation of the dura by 65% at 10 mg kg(-1) Morphine (3 mg kg(-1)) also inhibited t he TNC neuronal sensitization following CGRP-evoked dilation. 4 The present studies have demonstrated that opioids block the nociceptive neurotransmission within the trigeminal nucleus caudalis and in addition in hibit neurogenic dural vasodilation via an action on mu -opioid receptors l ocated on trigeminal sensory fibres innervating dural blood vessels. These peripheral and central actions are similar to those of the 'triptan' 6-HT1B /1D agonists and could account for the anti-migraine actions of opioids.