Morphine analgesia and the bulbospinal noradrenergic system: increase in the concentration of normetanephrine in the spinal cord of the rat caused by analgesics.

1 Administration of an analgesic dose (10 mg/kg, s.c.) of morphine increased the concentration of a noradrenaline metabolite, normetanephrine (NM) in the spinal cord of normal rats. The time course of the change in the NM concentration corresponded approximately to that of the morphine analgesia. The concentration of noradrenaline was not affected.2 A similar effect on the NM concentration was also observed after the administration of pentazocine (30 mg/kg, s.c.) and nalorphine (20 mg/kg, s.c.).3 The NM increasing effect of morphine, pentazocine and nalorphine was found in the dorsal half of the spinal cord but not in the ventral half.4 The increase in the concentration of NM induced by morphine, pentazocine or nalorphine was completely suppressed by naloxone (1 mg/kg, s.c.) given 5 min before the administration of these drugs.5 When the spinal cord was transected at C1, the NM increasing effect of morphine disappeared, yet when the brain stem was transected at the inter-collicular level, the effect remained.6 In morphine-tolerant rats, the concentration of NM in the spinal cord was almost the same as that observed in normal rats, but the increase in the concentration of NM in the spinal cord after the acute administration of morphine did not take place.7 The NM concentration in the spinal cord of normal rats was not modified by aminopyrine (75 mg/kg, s.c.), chlorpromazine (10 mg/kg, s.c.), mephenesin (100 mg/kg, i.p.) or naloxone (25 mg/kg, s.c.).8 The possible relation between morphine analgesia and the descending noradrenergic neurones in the spinal cord of rats is discussed.