dextrorphan and Spinal-Cord-Injuries

Within 3-4 weeks after spinal transection, morphine-induced antinociception, assessed with the tail flick reflex in rats, is profoundly reduced. The cause of this decrement is unknown. The present studies were conducted to determine whether this phenomenon reflects a general loss in opiate activity or a selective decline in opiate antinociception. This was accomplished by assessing the effect of morphine on two different responses, the tail flick reflex and the hindlimb spasticity that develops in chronic spinal rats. Because excitatory amino acid antagonists are also antinociceptive in acute spinal rats, the effect of one such drug, dextrorphan, on these two behaviors was also evaluated in chronic spinal animals. The antinociceptive and antispastic effect of subcutaneous (6 mg/kg) and intrathecal (5 micrograms) morphine injections were assessed in intact and chronic (21-28 days) spinal rats, whereas the effect of subcutaneous (25 and 40 mg/kg) and intrathecal (350 micrograms) dextrorphan was assessed in acute (1 day) and chronic spinal rats. The antinociceptive effect of both drugs was significantly reduced in chronic spinal animals, relative to saline controls. However, each drug treatment produced a significant antispastic effect in the same animals, indicating a selective decline in opiate action. This outcome also suggests that excitatory amino acid antagonists may be useful as adjunct antispastic agents.

Topics: Animals; Dextrorphan; Male; Morphine; Muscle, Skeletal; Narcotics; Pain Measurement; Rats; Spinal Cord Injuries; Time Factors

The potential role of N-methyl-D-aspartate (NMDA) receptors in the pathophysiology of spinal cord injury was examined in rats by comparing the effects of the non-competitive NMDA antagonist dextrorphan and the competitive NMDA antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) on the behavioral and anatomical consequences of impact trauma to the spinal cord. Treatment with either dextrorphan or CPP, administered intrathecally 15 min after trauma, significantly improved chronic (4 weeks) behavioral recovery. Treatment with CPP, but not dextrorphan, limited the decline in serotonin below the injury zone, as shown by both immunocytochemistry and high performance liquid chromatography. Beneficial effects of CPP were dose-dependent. Dextrorphan treatment also improved behavioral outcome when the drug was administered intravenously. These studies implicate NMDA receptor-mediated excitotoxins in tissue damage following spinal cord trauma and suggest that NMDA antagonists may be of value in the treatment of acute, clinical spinal cord injury.

Topics: Amino Acids; Animals; Anticonvulsants; Binding, Competitive; Dextrorphan; Injections, Spinal; Male; Morphinans; Motor Activity; Piperazines; Rats; Rats, Inbred Strains; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter; Spinal Cord Injuries