The neuropeptide FF analogue, 1DME, enhances in vivo met-enkephalin release from the rat spinal cord

Behavioural studies have suggested that endogenous opioids mediate the anti nociceptive action of neuropeptide FF (FLFQPQRF-NH2) at the spinal level in the rat. This hypothesis was directly assessed by investigating the effect s of a NPFF analogue, 1DMe ([D-Tyr(1),(NMe)Phe(3)]NPFF), on the spinal outf low of met-enkephalin-like material (MELM) in halothane-anaesthetised rats. Intrathecal infusion (0.1 ml/min) of 1DMe (0.1 mu M-0.1 mM, for 45 min) pr oduced a concentration-dependent increase in spinal MELM outflow which pers isted for at least 90 min at the highest concentration tested. Intrathecal coadministration of the mu-opioid receptor antagonist CTOP (1 mu M) did not significantly affect the spinal MELM overflow due to 0.1 mM 1 DMe. In cont rast, both naltrindole and nor-binaltorphimine, at concentrations (10 mu M) that allow the selective blockade of partial derivative- and kappa-opioid receptors, respectively; significantly reduced the stimulatory effect of 1D Me on spinal MELM outflow. These data provide the first direct demonstratio n that met-enkephalin (among other opioid peptides) can mediate the antinoc iceptive action of NPFF at the spinal level in rats. In addition, they sugg est that reciprocal excitatory interactions between opioids and opioid-modu latory factors (such as NPFF) participate in the physiological control of n ociception. (C) 1999 Elsevier Science Ltd. All rights reserved.