Pharmacological interaction between neuropeptides and pethidine or fentanyl in rat spinal cord.

Male Wistar rats were treated with pethidine (PT) or fentanyl (FN) subcutaneously (sc) followed by intrathecal (ith) non analgesic doses of methionine- (MENK) or leucine-enkephalin (LENK), neurotensin, (NT), substance P (SP) or cholecystokinin octapeptide 26-33 (CCK-8). Then the antinociceptive effect was measured during 1 h using tail-immersion test. LENK potentiated strongly PT and FN analgesia. MENK antagonized PT analgesia only transiently 30 min after administration and transiently potentiated FN analgesia. SP and CCK-8 potentiated significantly PT analgesia, whereas NT acted biphasically: increasing and then decreasing PT analgesia. SP, CCK-8 and NT augmented FN analgesia. Naloxone inhibited analgesia elicited by the studied opioids and neuropeptides. These data show that LENK affects similarly the analgesic effects of both studied opioids, whereas MENK acted differently on PT and FN analgesia. This may suggest that individual enkephalins have different pharmacological features when interacting with different analgesics. Also NT interacted differently with pethidine and fentanyl.