Role of nociceptin/orphanin FQ and the pseudopeptide [Phe1Ψ(CH2NH)Gly2]-nociceptin(1–13)-NH2 and their interaction with classic opioids in the modulation of thermonociception in the land snail Helix aspersa

The role in nociception of nociceptin/orphanin FQ (N/OFQ) and its receptor, the opioid receptor-like 1 (NOP), remains unclear because this peptide has been implicated in both suppression and enhancement of nociception. The present work characterises the effects of N/OFQ and the NOP receptor antagonist, the pseudopeptide [Phe1Ψ(CH2NH)Gly2]-nociceptin(1–13)-NH2 (Phe1Ψ), on thermonociception in the snail Helix aspersa using the hot plate assay. Additionally, the possible interaction of each of these compounds with morphine or dynorphin A1–17 and naloxone was studied. Compounds were administered into the hemocoel cavity of H. aspersa and the latency to the aversive withdrawal behaviour recorded. Dose–response and time course curves were done. N/OFQ and naloxone produced a similar dose-dependent pronociceptive effect; however, N/OFQ reached its peak effect earlier and was 30 times more potent than naloxone. [Phe1Ψ(CH2NH)Gly2]-nociceptin(1–13)-NH2 and the opioid agonists, morphine and dynorphin A1–17 produced antinociception with a similar efficacy, but [Phe1Ψ(CH2NH)Gly2]-nociceptin(1–13)-NH2 reached its peak effect more rapidly and lasted longer than that of dynorphin A1–17 and morphine. [Phe1Ψ(CH2NH)Gly2]-nociceptin(1–13)-NH2 was 50 times less potent than dynorphin A1–17, but 30 times more potent than morphine. N/OFQ significantly reduced morphine and dynorphin A1–17-induced antinociception. Combined administration of low doses of [Phe1Ψ(CH2NH)Gly2]-nociceptin(1–13)-NH2 and morphine or dynorphin A1–17 produced a potent antinociceptive effect. Sub-effective doses of naloxone and N/OFQ also synergised to produce pronociception. Data suggest that these two opioid classes regulate nociception through parallel systems. The H. aspersa model appears as a valuable experimental preparation to continue the study of these opioid receptor systems.