Tolerance to the antinociceptive effect of intrathecal morphine in intact and chronic spinal rats

The antinociceptive effect of daily acute intrathecal morphine injections on the tail-flick withdrawal response was compared in Intact rats and rats that were spinally transected 3 to 4 weeks prior to morphine administration (Spinal rats). Spinal rats became tolerant to repeated intrathecal injections of 5, 15, or 30 micrograms of morphine within 3 days. Intact rats were not tolerant to these doses after 4 daily injections. Spinal rats, made tolerant to repeated intrathecal morphine injections, were not tolerant to a subcutaneous injection of 6.0 mg/kg of morphine. These data suggest that, in intact animals, tolerance to the antinociceptive effect of spinal morphine is modulated by descending, supraspinal input.