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–NH 2) 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 μM–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 μ-opioid receptor antagonist CTOP (1 μM) did not significantly affect the spinal MELM overflow due to 0.1 mM 1DMe. In contrast, both naltrindole and nor-binaltorphimine, at concentrations (10 μM) that allow the selective blockade of ∂- and κ-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.