Effect of 5-hydroxytryptamine precursors on morphine analgesia in the formalin test

The 5-hydroxytryptamine (5HT) precursors tryptophan and 5-hydroxytryptophan had no significant effect on the behavior of rats in the formalin test when given by themselves. However, both compounds significantly attenuated the analgesic effect of morphine in the formalin test. The 5HT antagonist methysergide enhanced the antinociceptive effect of morphine but systemic 5HT had no effect. Assays of whole brain and spinal cord indoles revealed different patterns as a result of tryptophan or 5-hydroxytryptophan loading. The effect common to both treatments was an increase in brain 5HT. There was no effect of morphine on any measure. Formalin injection by itself did not alter indole levels in the brain or spinal cord. Our results, taken in conjunction with previous work, suggest that 1) 5HT in the spinal cord does not influence pain perception in the formalin test and 2) 5HT in the brain can antagonize morphine analgesia in the formalin test. We conclude that there may be circumstances in which the use of 5HT precursors for clinical pain management may be contraindicated.