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 antinociceptive action of neuropeptide FF (FLFQPQRF-NH2) at the spinal level in the rat. This hypothesis was directly assessed by investigating the effects of a NPFF analogue, 1DMe ([D-Tyr(1),(NMe)Phe(3)]NPFF), on the spinal outflow 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) produced a concentration-dependent increase in spinal MELM outflow which persisted 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 contrast, 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 1DMe on spinal MELM outflow. These data provide the first direct demonstration that met-enkephalin (among other opioid peptides) can mediate the antinociceptive action of NPFF at the spinal level in rats. In addition, they suggest that reciprocal excitatory interactions between opioids and opioid-modulatory factors (such as NPFF) participate in the physiological control of nociception. (C) 1999 Elsevier Science Ltd. All rights reserved.