The Role of the Dorsolateral Pontine Tegmentum in Modulating Nociception

Abstract

Compelling evidence exists for the role of supraspinal centers in the modulation of nociception. For example, numerous studies have established that stimulation of the spinally-projecting serotonergic neurons in the ventromedial medulla (VMM) inhibits nociception. Several sites within the brainstem are known to innervate the VMM, including the periaqueductal gray (PAG) as well as other sites. Experiments performed in our laboratory have demonstrated that some neurons in the dorsolateral pontine tegmentum (DLPT) have dense projections to the VMM and appear to modulate nociception. The purpose of this research was to investigate the anatomical and functional role of these projections from the DLPT to the VMM.

The first set of experiments examined the anatomical projections from the DLPT to the VMM using both anterograde and retrograde tracers combined with immunocytochemistry. These studies revealed that cell bodies within the DLPT, specifically within the region of the A7 cell group but not including those noradrenergic cells, project diffusely to the VMM.

The second series of experiments explored the effect of electrical stimulation of the DLPT on paw withdrawal latencies. Electrical stimulation of the DLPT evoked antinociception that was blocked by the intrathecal administration of serotonergic antagonists, including methysergide and propranolol, but not by saline. These findings provide additional evidence that the antinociception derived from electrical stimulation of the DLPT is mediated, in part, by spinally-projecting serotonergic neurons.

The final group of experiments determined whether selective activation of neurons, but not axons of passage, could produce antinociception. The excitatory amino acid, glutamate, was used to selectively activate DLPT neurons. Glutamate microinjection produced a brief antinociceptive effect that was blocked by the microinjection of the local anesthetic tetracaine into the VMM.

The results of these experiments indicate that the non-noradrenergic neurons within the DLPT project to serotonin-containing neurons of the VMM and that these projections are involved in the modulation of nociception.