1DMe, a
neuropeptide FF (
NPFF) analogue, has been shown to produce antinociception and to enhance
morphine analgesia in rats after intrathecal administration. To determine whether 1DMe could correct
hyperalgesia and restore
morphine efficacy in mononeuropathic (MN) and diabetic (D) rats we examined the spinal effect of 1DMe in MN and D rats without and after spinal blockade of mu- and
delta-opioid receptors with
CTOP and
naltrindole, respectively. The influence of 1DMe on
morphine-induced antinociception was assessed in the two models using isobolographic analysis. Whereas 1DMe intrathecally injected (0.1, 1, 7.5 microg rat(-1)) was ineffective in normal (N) rats, it suppressed
mechanical hyperalgesia (decrease in paw pressure-induced vocalisation thresholds) in both MN and D rats. This effect was completely cancelled by
CTOP (10 microg rat(-1)) and
naltrindole (1 microg rat(-1)) suggesting that it requires the simultaneous availability of mu- and
delta-opioid receptors. The combinations of
morphine: 1DMe (80.6:19.4% and 99.8:0.2%, in MN and D rats, respectively) followed by isobolographic analysis, showed a superadditive interaction, relative to the antinociceptive effect of single doses, in D rats only. In N rats, the combination of
morphine: 1DMe (0.5 mg kg(-1), i.v.: 1 microg rat(-1), i.t., ineffective doses) resulted in a weak short-lasting antinociceptive effect. These results show a different efficacy of 1DMe according to the
pain model used, suggesting that the pro-
opioid effects of the
NPFF in
neuropathic pain are only weak, which should contribute to
hyperalgesia and to the impaired efficacy of
morphine.