Substance P, injected intrathecally, antagonizes the spinal antinociceptive effect of morphine, baclofen and noradrenaline.

The effect of substance P on the antinociceptive effect of morphine, baclofen and noradrenaline in the spinal cord was examined in the tail-flick and hot plate tests, after intrathecal administration. Substance P (5-20 micrograms) produced a dose-related antagonism of the effect of all three agents, which persisted for the entire time-course of the antinociceptive effect in each case. The rank order of potency of substance P and related peptides in antagonizing the antinociceptive effect of morphine, was substance P greater than physalaemin greater than eledoisin greater than eledoisin-related peptide. A similar order of potency was observed against noradrenaline, except that physalaemin appeared to be the most potent. The intrathecal administration of these peptides did not alter reaction latencies in the tail-flick test when baseline values were 2-3 sec, but produced a significant decrease in latency (hyperalgesia) when baseline values were 6-8 sec. There was a slight increase in reaction latency in the hot plate test. The specificity of the antagonism was examined by determining the effect of phentolamine on the antinociceptive effect of morphine and baclofen. Although phentolamine (30 micrograms) produced comparable hyperalgesia to substance P, it did not significantly alter the antinociceptive effect of morphine or baclofen. These results suggest that alterations in the function of substance P in the spinal cord may contribute to the spinal antinociceptive effects of morphine, baclofen and noradrenaline. The effects of substance P on nociception in the spinal cord appear to be mediated by substance P type receptors.