An analgesic effect of enkephalinase inhibition is modulated by monoamine oxidase-B and REM sleep deprivations.

Both the MAO-B inhibitor deprenyl (2.5-10 mg/kg, ip, 60 min prior) and the MAO-B substrate beta-phenylethylamine (PEA, 40 micrograms, icv) potentiated the analgesic action of the enkephalinase inhibitor phosphoramidon (250 micrograms, icv) in animals allowed normal sleep. The enhancing effect of PEA on phosphoramidon analgesia was further potentiated by deprenyl (5 mg/kg, ip) pretreatment. Deprenyl (5 mg/kg, ip) or PEA (40 micrograms, iv) given alone did not induce analgesia in animals allowed undisturbed sleep. REM sleep deprivation (REMSD) decreased the basal pain threshold and abolished the analgesic effect of phosphoramidon. The administration of deprenyl and/or PEA failed to restore the analgesic effect of phosphoramidon in REM sleep deprived animals. The results indicate that excess PEA has a stimulatory effect on the analgesic activity of endogenously released enkephalins in rats allowed undisturbed sleep but not in REM sleep deprived animals. It is suggested that the failure of phosphoramidon to induce analgesia after REMSD, is probably due to a functional insufficiency of an enkephalinergic system.