The ORL-1 (NOP 1) receptor ligand nociceptin/orphanin FQ (N/OFQ) inhibits neurogenic dural vasodilatation in the rat

Abstract

The effects of the ORL-1 (NOP 1) receptor ligand nociceptin (N/OFQ) and the nociceptin antagonists [Nphe 1]N/OFQ-(1-13)-NH 2 (Nphe) and nocistatin (NST) on neurogenic dural vasodilatation (NDV) in the rat dura mater evoked by electrical stimulation of a closed cranial window were studied. The middle meningeal artery was visualised using intravital microscopy, and the vessel diameter analysed using a video dimension analyser. N/OFQ (1, 10, 100 nmol kg −1; i.v., n=10) significantly and dose-dependently suppressed NDV maximally by 65% ( P<0.01). Neither Nphe (100 nmol kg −1; n=5) nor NST (100 nmol kg −1; n=4) alone had an effect on NDV ( P>0.05). Baseline vessel diameter was not significantly affected by application of N/OFQ, NST or Nphe. Application of the selective N/OFQ antagonist Nphe (10, 100 nmol kg −1 i.v., n=8) dose-dependently and significantly ( P<0.01) reversed the inhibition of NDV induced by application of N/OFQ (10 nmol kg −1). NST (10, 100 nmol kg −1; n=7) failed to reverse the effects elicited by N/OFQ. Application of N/OFQ elicited a dose-dependent transient decrease in arterial blood pressure ( P<0.01). Nphe dose-dependently reversed the cardiovascular effects induced by application of N/OFQ (10 nmol kg −1) ( P<0.01),while NST did not alter the blood pressure reaction elicited by N/OFQ. The results show that N/OFQ inhibits NDV, an effect which is antagonised by Nphe, but not by NST. ORL-1 (NOP 1) receptors located on trigeminal sensory fibres may be involved in the regulation of dural vessel diameter and hence may play a role in migraine pathophysiology.