Dynorphin: potent analgesic effect in spinal cord of the rat

Evidences are presented to show a strong and long-lasting analgesic effect after injection of dynorphin into the subarachnoid space of the spinal cord in the rat. Taking the amplitude and time course of the increase of tail flick latency as the indices of analgesia, dynorphin elicited dose-dependent analgesic effect in the range of 2.3-18.6 nmol. Calculating on a molar basis dynorphin was 6-10 times more potent than morphine and 65-100 times more potent than morphiceptin, another mu opiate receptor agonist. Dynorphin analgesia was completely reversed by intrathecal injection of anti-dynorphin IgG and partially reversed by naloxone. Acute tolerance to morphine analgesia did not affect the occurrence of dynorphin analgesia, indicating the absence of cross tolerance between morphine and dynorphin. Evidence from different lines of approach suggests that dynorphin may bind with kappa opiate receptors in the spinal cord to exert its analgesic effect.