Tolerance to the antinociceptive effect of morphine in spinally transected rats

The effect of a spinal transection on morphine-induced tolerance in rats was examined with the tail withdrawal reflex (tail flick; TF), elicited by noxious thermal stimulation. Intact rats became tolerant to sc morphine injections (3.0 mg/kg) if they were tested on the TF after each injection. Morphine administration alone did not produce tolerance; tail flick tests alone did, though not always to a significant extent. However, when morphine only, TF tests only, or both were administered prior to transection (acute spinal rats), all groups were tolerant when tested 1 day after spinalization. When the same treatments were administered to rats 3 weeks after spinal transection (chronic spinal rats), neither morphine nor TF tests alone produced tolerance. Chronic spinal rats became tolerant only if they were tested after each injection. These results suggest, first that tolerance develops at the spinal cord as a result of either chronic opiate exposure or performance of the nociceptive response but that, intact rats, tolerance is inhibited or suppressed by a supraspinal action of morphine. Second, the fact that chronic spinal rats did not become tolerant to morphine or TF tests alone suggests either that such tolerance is mediated by descending input or that spinal transection produces intrinsic changes in the spinal cord that preclude the development of tolerance induced only by opiate or behavioral stimulation.