Inhibition of spinal dorsal horn neuronal responses to noxious skin heating by lateral hypothalamic stimulation in the cat.

The responses of single lumbar dorsal horn units to noxious radiant heating (50 degrees C, 10 s) of glabrous foot pad skin were recorded in cats anesthetized with sodium pentobarbital and 70% N2O. The heat-evoked responses of each of 38 units were markedly reduced during electrical stimulation (100-ms trains at 100 Hz, 3/s, 25-300 microA) in the lateral hypothalamic area (LH). LH sites at which stimulation inhibited dorsal horn unit heat-evoked responses were mapped by systematically varying the position of the stimulating electrode. Inhibition was generated at posterior through anterior hypothalamic levels in a region extending laterally from the periventricular gray (PVG) to the cerebral peduncles on both sides and ventrally to the base of the brain. The magnitude of inhibition increased with graded increases in LH stimulation intensity. Respective mean current intensities at threshold for generating inhibition were 27.6 +/- 17.4 (SD) microA for contralateral and 30.1 +/- 23.7 microA for ipsilateral LH stimulation. Dorsal horn unit responses to a series of graded noxious heat stimuli generally increased linearly from threshold (38-45 degrees C) to 52 degrees C. The slopes of such linear temperature-response functions were reduced, with no significant change in threshold, when the temperature series was repeated during concomitant ipsilateral LH stimulation. Contralateral LH stimulation produced similar slope reductions but additionally produced a significant mean threshold increase of 1.7 degrees C. The inhibitory effect of LH stimulation was significantly reduced in nine units from a mean of 28 +/- 18% of control to a mean of 59 +/- 18% following systemic administration of the serotonin (5-hydroxytryptamine, 5-HT) antagonist, methysergide (0.3-1 mg/kg). Possible functional relationships of LH with brain stem inhibitory systems and its role in analgesic mechanisms are discussed.

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

Electrical stimulation in the midbrain periaqueductal gray (PAG) and lateral midbrain reticular formation (LRF) 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 [14,15] 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 degrees C, 10 sec, 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 microA 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 microA to 60% of control in 12 units) was not detectably different from that in control (non-pretreated) cats. However, 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. In contrast, 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. The results suggest pharmacologically distinct mechanisms of inhibition produced by stimulation in PAG and LRF.