THE PERMISSIVE ACTION OF GLUCOCORTICOID ON THE ANALGESIC EFFECT OF KYOTORPHIN AND ITS ANALOGUE

Kyotorphin (KTP) is an endogenous analgesic dipeptide which does not act on opiate receptors but may induce the release of endogenous opioid met-enkephalin. In order to investigate whether or not glucocorticoids have "permissive action" on KTP, hydrocortisone has been used to examine its action on the analgesic activities of KTP and its retro-isomer (riKTP) by employing thermal irradiation-tail flick method after intracerebroventricular injection.KTP and riKTP showed dose-dependent analgesic activity. Dose of KTP in the range of 6～24 mmol/L were effective, while the dose of riKTP at 6 mmol/L was shown to be ineffective. The analgesia of KTP was higher than that of riKTP. Hydrocortisone alone showed no significant analgesic effect. Linkers by connecting hydrocortisone with KTP or riKTP showed significantly higher analgesic effect compared with the corresponding dipeptides, not only in the duration of analgesia but also in potency. Solutions containing hydrocortisone and any one of the dipeptides exhibited the same effect as the linker. Pretreatment with sc naloxone (10 mg/kg) 15 min before icy of KTP or riKTP (24 mmol/L) could not block the analgesia.These findings implicate that: (1) Glucocorticoids have a permissive action on the analgesia of KTP and its retro-isomer. The glucocortieoids may exert its effects by acting on receptors in the membrane, and thus cause fast membrane effect. (2) KTP may also induce release of substances other than met-enkephalin to participate in the analgesia.