The antinociceptive role of a bulbospinal serotonergic pathway in the rat brain

The antinociceptive role of spinal serotonin (5-HT) neurons descending from 5-HT cells near the ventrolateral surface of the medulla oblongata was investigated by stimulating these cells in normal rats, in rats with generalized or selective chemical ablation of 5-HT nerves, and in rats with postsynaptic blockade of 5-HT receptors. Electrical stimulation of the lateral medulla elicited analgesia in normal rats; the increase in pain threshold was proportional to the intensity and to the frequency of stimulation. In addition, microinjection of kainic acid or L-glutamate at the same sites also produced analgesia. However, generalized destruction of CNS 5-HT nerves produced by intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) or selective destruction of spinal 5-HT nerves produced by intraspinal injection of 5,7-DHT reduced the magnitude of the antinociceptive responses to electrical stimulation. Postsynaptic blockade of CNS 5-HT receptors produced by intraventricular injection of cyproheptadine also reduced the stimulation-produced analgesia. The specificity of the lesions for 5-HT nerves is demonstrated by the lack of effect on the levels of noradrenaline in the same brain regions. The results indicate that the activity of 5-HT nerve cells adjacent to the ventrolateral surface of the medulla oblongata and projecting to the spinal cord serves to elevate pain threshold.