Role of opioid receptors in the spinal antinociceptive effects of neuropeptide FF analogues

Abstract

1 Neuropeptide FF (NPFF) has been shown to produce antinociceptive effects and enhance morphineinduced antinociception after intrathecal (i.t.) injection. In this study, the spinal effects of two NPFF analogues, [D-Tyr',(NMe) (11 nmol 5 The results of this study show that spinal ,-and 6-opioid receptors play a role in antinociception produced by NPFF analogues. These results also suggest a role for NPFF in modulation of nociceptive signals at the spinal level.

Neuropeptide FF Receptors Have Opposing Modulatory Effects on Nociception

“…Although it remains plausible that NPFF agonists can potentiate the antinociceptive actions of opioids (Kontinen and Kalso, 1995;Gouardères et al, 1996;Xu et al, 1999), depending on the route of administration, this possibility was beyond the scope of the present investigation. Given the lack of activity of AC-263093 on acute sensory thresholds, we also profiled this compound in the formalin and carrageenan models.…”

“…Although "classically" NPFF is characterized as an antiopioid peptide, it has been shown to also elicit robust antinociceptive effects depending on the dose and route of administration used (for review, see Yang et al, 2008). For example, intrathecal administration of NPFF or of its stable analog [D-Tyr 1 ,(NMe)Phe 3 ]NPFF (1DMe) either elicits antinociception or potentiates the antinociceptive effect of morphine (Kontinen and Kalso, 1995;Gouardères et al, 1996;Xu et al, 1999). In contrast, intracerebroventricular administration of these agents antagonizes morphine-induced antinociception (Gicquel et al, 1992;Oberling et al, 1993;Dupouy and Zajac, 1995).…”

Identification and Characterization of Two G Protein-coupled Receptors for Neuropeptide FF

“…There is a large body of evidence suggesting that NPFF is involved in nociception and in the modulation of opiate-induced analgesia, morphine tolerance, and morphine abstinence (3)(4)(5)(6)(7)(8)(9)(10)(11). Interestingly, NPFF possesses both anti-opioid and pro-opioid actions in animal models of pain.…”

Identification of proNeuropeptide FFA peptides processed in neuronal and non‐neuronal cells and in nervous tissue

“…There is a large body of evidence that NPFF exhibits antiopioid properties; in rodents, morphine-induced analgesia decreased following administration of NPFF or NPFF analogues and increased, as stress-induced analgesia, in response to anti-NPFF antibody administration [6][7][8]. In contrast, intrathecal injections of NPFF analogues induced a long-lasting analgesia [9,10] by increasing opioid peptide release in the spinal cord through the functional blockade of presynaptic delta-opioid autoreceptors [11,12]. Recent data provided evidence that opioid and NPFF endogenous systems exert a tonic activity, NPFF counteracting tonic opioid analgesia under resting conditions [13].…”

“…In contrast, intrathecal injections of NPFF analogues induced a long-lasting analgesia [9,10] by increasing opioid peptide release in the spinal cord through the functional blockade of presynaptic delta-opioid autoreceptors [11,12]. Recent data provided evidence that opioid and NPFF endogenous systems exert a tonic activity, NPFF counteracting tonic opioid analgesia under resting conditions [13].…”