An ascending serotonergic pain modulation pathway from the dorsal raphe nucleus to the parafascicularis nucleus of the thalamus.

Three types of spontaneously active neurons were found in the parafascicularis (PF) nucleus of the thalamus of the rat: slow firing units (0.5-10 spikes/s), bursting units (2-5 spikes/burst in 10-20 ms, one burst every 1-2 s) and fast firing units (15-40 spikes/s). A similar population of neurons was found in the PF of rats treated with 5,7-dihydroxytryptamine (5,7-DHT), a serotonin neurotoxin. Noxious tail pinch (TP) caused 68% of the PF neurons to increase their firing rates to 242% of their initial baseline activity, while non-noxious touch stimulation failed to induce a response. In the 5,7-DHT-treated rats, TP caused 85% of the neurons in the PF to increase their firing rates to 581% of their initial baseline activity and 22% of the neurons increased their firing in response to touching the tail. Both the number of cells responding (P less than 0.05) and the percentage increase (P less than 0.001) were statistically greater in serotonin-depleted rats than in controls. This indicates that serotonin (5-HT) has a tonic inhibitory influence on responses to both noxious and non-noxious sensory stimuli. In control rats, electrical stimulation of the dorsal raphe nucleus (DR) decreased the firing rates of PF neurons. In contrast, the same DR stimulation induced an increase in PF firing rates during stimulation in serotonin-depleted rats and this increase in firing rates remained several seconds after cessation of stimulation. This indicates that the DR may use at least two different neurotransmitters in its projections to forebrain structures. In control rats, the TP stimulation induced an increase in firing rates of rates of PF neurons while DR stimulation attenuated the excitation induced by TP stimulation. In serotonin-depleted rats, DR stimulation and TP both caused an increase in firing rates. This effect was not additive indicating that there may be a serotonergic projection from the DR to the PF which modifies responses to somatosensory stimuli. The inhibitory effects elicited by electrical stimulation were limited to the immediate area of the DR. Stimulation of the adjacent reticular formation 1 mm lateral to the DR produced the opposite effect, an increase in firing rate often accompanied by driven spike activity in the PF.