Studies on the intrathecal effect of beta-endorphin in primate

The intrathecal administration of beta-endorphin in the primate through an indwelling spinal catheter, produced a significant elevation in the nociceptive threshold as measured by the discrete trial shock titration task. The time of onset, duration of effect and magnitude of effect were all dose-dependent over a range of 150-750 micrograms. The effects were antagonized in a dose-dependent fashion by the systemic administration of naloxone. Aside from the elevations in the shock titration threshold produced by intrathecal beta-endorphin, no untoward effects on the animal's motor function or behavioral reactivity was noted. Significantly, unlike morphine, intrathecal beta-endorphin failed to produce any signs of scratching behavior at the doses used in these experiments. Once daily administration of intrathecal beta-endorphin (500 micrograms) showed a significant progressive decline in the antinociceptive effect over an 8-day period. Animals made tolerant to beta-endorphin in this fashion showed a significantly reduced response to an otherwise active dose of intrathecal morphine, indicating evidence for cross tolerance.