Antinociceptive effect of intrathecal morphine in tolerant and nontolerant spinal rats

Abstract

The antinociceptive effect of intrathecal morphine on the tail-flick (TF) reflex of rats was significantly enhanced within one day after spinal transection (ED50 = 0.125 microgram) relative to the effect obtained in intact rats (ED50 = 5.9 micrograms). By 20-30 days after spinalization the potency of intrathecally administered morphine had substantially declined. Intact rats, made tolerant to the antinociceptive effect of systemic morphine (3.0 mg/kg, SC on each of seven consecutive days), were not tolerant to intrathecal morphine (ED50 = 6.5 micrograms). In contrast, rats that were pretreated with either morphine alone, repeated TF tests alone, or both of these treatments, were tolerant to intrathecal morphine when tested one day after spinal transection. The results suggest first, that the antinociceptive effect of intrathecal morphine in intact rats is tonically inhibited by descending supraspinal input and that removal of this input is responsible for the enhanced antinociceptive effect of intrathecal morphine in spinal rats. Second, the data suggest that tolerance to the antinociceptive effect of intrathecal morphine in intact rats may also be tonically inhibited by supraspinal input, because spinal opiate tolerance is expressed after spinal transection.