Pronociceptive effects of the neuropeptide, nociceptin, in the land snail, Cepaea nemoralis.

The peptide, Phe-Gly Phe-Thr-Gly-Ala-Arg-Lys-Ser-Ala-Arg-Lys-Leu-Ala-Asn-Gln-OH, recently isolated from rat brain, has been suggested to be an endogenous agonist for an orphan, opioid-like receptor (ORL1). This peptide, called "nociceptin" (or orphanin FQ), has been suggested to have pronociceptive, hyperalgesic functions. The present study examined the effects of nociceptin on aversive thermal (nociceptive) responses in an invertebrate, the land snail, Cepaea nemoralis. Nociceptin had significant, dose-related pro-nociceptive effects in Cepaea, whereas the opioid peptide, dynorphin A, which shares some sequence similarities with nociceptin, had significant antinociceptive effects. The effects of dynorphin were blocked by the kappa-opiate receptor antagonist, nor-binaltorphimine, whereas those of nociceptin were unaffected. Repeated daily administrations of nociceptin resulted in reduced pronociceptive effects, suggestive of the development of tolerance to the hyperalgesic actions of this opioid-related peptide. These findings suggest that the novel peptide, nociceptin, can influence nociceptive responses in the snail, Cepaea, in a manner similar to that indicated for rodents.