Selective innervation of lamina I projection neurones that possess the neurokinin 1 receptor by serotonin-containing axons in the rat spinal cord.

Axons containing serotonin descend from brainstem to spinal cord and are thought to contribute to stimulation-produced and opioid analgesia, partly by a direct inhibitory action of serotonin on projection neurones. The density of serotoninergic innervation is highest in lamina I, which contains many nociceptive projection neurones. Two sets of anatomical criteria have been used to classify lamina I projection neurones: somatodendritic morphology and presence or absence of the neurokinin 1 receptor. To test whether the strength of serotoninergic innervation of lamina I projection neurones was related to morphology or neurokinin 1 receptor expression, we used confocal microscopy to determine the density of serotoninergic contacts on 60 cells retrogradely labelled from the caudal ventrolateral medulla. The contact density on neurones with the neurokinin 1 receptor was variable, with some cells receiving heavy input and others having few contacts. However, on average they received significantly more contacts (5.64 per 1000 microm(2) plasma membrane +/- 0.47, S.E.M.) than neurones which lacked the receptor (2.49 +/- .36). Among the neurokinin 1 neurones, serotoninergic innervation density was not related to morphology. Since the majority of serotoninergic boutons in lamina I of rat spinal cord do not appear to form synapses, we carried out electron microscopy on three heavily innervated neurokinin 1 receptor-immunoreactive projection neurones. Symmetrical synapses were found at 89% of serotoninergic contacts. These results indicate that serotoninergic innervation of lamina I projection neurones in the rat spinal cord is related to expression of neurokinin 1 receptors, but not to morphology, and that (at least on heavily innervated neurones) most serotonin-containing boutons which are in contact form synapses.