Serotonergic mediation of descending inhibition from midbrain periaqueductal gray, but not reticular formation, of spinal nociceptive transmission in the cat

Abstract

Electrical stimulation in the midbrain periaqueductal gray (PAG) and lateral midbrain reticular formation (LRF) of the cat strongly suppresses the responses of spinal dorsal horn neurons to noxious heating of the skin. The possible role of serotonin (5-hydroxytryptamine, 5-HT) was investigated by quantitatively comparing certain parameters of descending inhibition from PAG and LRF in normal cats and cats whose central 5-HT levels had been reduced by pretreatment with p-chlorophenylalanine (PCPA, 300 or 500 mg/kg i.p., 72 h prior to acute experiment). Single lumbar dorsal horn neuronal responses to noxious radiant heating of glabrous footpad skin (50.degree. C, 10 s, 1/3 min) were recorded in normal and PCPA-pretreated cats anesthetized with sodium pentobarbital and N2O. Inhibition of neuronal heat-evoked responses during midbrain stimulation (mean frequency 30 Hz, up to 800 .mu.A current intensity) was expressed as percent of the unit''s control response in the absence of midbrain stimulation. Inhibition by PAG stimulation of units from cats pretreated with 300 mg/kg PCPA (mean inhibition at 450 .mu.A to 60% of control in 12 units) was not detectably different from that in control (non-pretreated) cats. Inhibition by PAG stimulation was significantly weaker in units from cats pretreated with 500 mg/kg PCPA (mean to 83.4% of control in 9 units). In the latter group mean current threshold for inhibition was higher and slope of current-intensity plots lower than in the control and 300 mg/kg PCPA pretreatment groups. Mean inhibition by LRF stimulation was enhanced in the 300 and 500 mg/kg PCPA treatment groups in a dose-related manner. In normal (non-pretreated) cats systemic administration of the putative 5-HT antagonist methysergide (0.07-1 mg/kg) reduced or abolished inhibition by PAG stimulation in each of 8 units. Low doses of methysergide had little or no effect on inhibition produced by LRF stimulation in 6 units. Pharmacologically distinct mechanisms of inhibition are produced by stimulation in PAG and LRF.