1. The responses of primate spinothalamic tract cells innervating the glabrous skin of the foot to noxious thermal stimuli have been examined. 2. Of the 41 cells studied, 98% responded to noxious thermal stimuli. Heating the cutaneous receptive field with a series of stimuli from 35 to 43, 47, and 50 degrees C produced a graded increase in discharge rate. The responses were characterized by an onset, which occurred after the temperature change had either slowed or stopped, an acceleration in the discharge up to a peak, and then an adaptation to a new base-line level. The time constants of adaptation were faster than those reported for C polymodal nociceptors. 3. No systematic differences were found in the responses to noxious thermal stimuli of cells with wide dynamic range receptive fields and of cells with narrow dynamic range, high-threshold receptive fields. There were also no differences in the responses of cells located in the marginal zone and of cells located in the neck of the dorsal horn. 4. The relationship between peak frequency and final skin temperature with a 30 s stimulus duration can best be described by a power function with an exponent of 2.1. An increase in the stimulus duration to 120 s resulted in an increase in the exponent of the power function to 3.2. 5. Repetition of the series of 30-s heat stimuli resulted in an increase in peak frequency, total impulse count, and background activity. Repetition of stimuli having a duration of 120 s produced an increase in the peak frequency at 43 and 45 degrees C, a smaller increase at 47 degrees C, and a decrease at 50 degrees C. Background activity was increased by the lower temperature stimuli, but was decreased following higher temperature stimuli. 6. In six additional cells, the skin was heated with three consecutive presentations at each temperature level (43, 45, 47, and 50 degrees C) for 30 s. No change was observed in the peak frequencies of the responses to successive stimuli of the same intensity. However, the exponent of the power function relating the average peak frequency for the six cells to changes in skin temperature was 3.9. This exponent was larger than that seen when two series of graded heat stimuli of 120 s duration were used, indicating more sensitization despite the fact the total time of exposure to noxious heat was less. 7. A role for both high-threshold and wide dynamic range spinothalamic cells in transmitting nociceptive information to the diencephalon is postulated.

The effects of glutamate (Glu), gamma-aminobutyric acid (GABA), glycine (Gly), serotonin (5-HT), norepinephrine (NE), dopamine (DA), and acetylcholine (ACh) were examined in this study by iontophoretic application onto primate spinothalamic tract (STT) neurons identified antidromically by stimulation in the contralateral thalamus. Drugs were tested for effects on background activity, Glu-induced firing, and activity evoked by pinching of the skin. Whereas Glu excited STT cells and was thus used for tests of the other compounds, the amino acids GABA and Gly inhibited Glu- and pinch-induced activity in all STT cells examined. STT cells were also inhibited by 5-HT, NE, and DA. Only two cases of excitation by 5-HT were seen (of 58 cells tested). ACh also had inhibitory actions on STT cells, although 3 of 21 cells exhibited some enhancement of activity. The effects of these compounds on identified STT cells resemble previous demonstrations of the effects of these drugs on dorsal horn interneurons. The results suggest that GABA, Gly, 5-HT, NE, and DA may be inhibitory neurotransmitters on nociceptive STT cells.

The activity of 132 neurons in the caudal part of the ventral posterior lateral nucleus (VPLc) of the thalamus was recorded from 23 anesthetized monkeys. All single thalamic units that could be excited by electrical search stimuli applied to the contralateral sciatic nerve were investigated. Responses of these cells to mechanical, thermal, and electrical stimuli applied in the periphery indicated that at least half of the sampled cells were nociceptive. Based on responses to graded mechanical stimuli applied to the periphery, 110 of the sampled cells that received a predominant input from cutaneous receptive fields were classified. There were 56 low-threshold, 39 wide dynamic range, and 15 high-threshold cells. The same neurons were also classified into five mechanical types based on a cluster analysis: types 1-5 contained 25, 34, 17, 10, and 24 cells, respectively. The fact that about half the population of cells belonged to either the wide dynamic or the high threshold group (or mechanical types 3-5) suggested that a large population of VPLc neurons respond to mechanical nociceptive stimuli either exclusively or preferentially. Responses of 63 thalamic neurons were tested to noxious heat pulses applied to their cutaneous receptive fields with a contact thermostimulator. Of these, 47 cells were excited, whereas only 16 cells did not respond. The peripheral nerve that innervated the receptive field of each of 82 thalamic neurons was stimulated with graded strengths to activate A fibers only or both A and C fibers. All tested cells responded to peripheral A fiber volleys. In addition, 42 of these cells responded to peripheral C fiber volleys. The C fiber responses could be either short lasting (a few hundreds of milliseconds) or long lasting (up to several seconds). The recording sites of 80 cells were reconstructed. Of these, 78 were in the VPLc nucleus and the remaining two were in the reticular nucleus of the thalamus. No obvious relationship between the response characteristics and the locations of the cells within the VPLc nucleus was found. Sampled thalamic units had a variety of sources of input from the periphery, including both cutaneous and/or deep tissue receptive fields. The majority of the cells, however, had exclusively cutaneous receptive fields. The sizes of the cutaneous receptive fields were often very small, so that nearly half (41%) of the receptive fields of cells sampled occupied an area of skin smaller than half the foot.(ABSTRACT TRUNCATED AT 400 WORDS)

1. The responses of spinothalamic tract cells in the lumbosacral spinal cords of anesthetized monkeys were examined following electrical stimulation of the sural nerve or the application of noxious thermal and mechanical stimuli to the skin on the lateral aspect of the foot. 2. The spinothalamic tract neurons were classified as wide dynamic range (WDR), high-threshold (HT), or low-threshold (LT) cells on the basis of their responses to mechanical stimuli. 3. All of the WDR and HT spinothalamic tract cells tested responded to volleys in A- and C-fibers. However, strong C-fiber responses were more common in HT than in WDR cells. 4. The responses atributed to C-fibers were graded with the size of the C-fiber volley. The latencies of the responses attributed to C-fibers indicated that the fastest afferents involved had a mean conduction velocity of 0.9 m/s. The responses remained after anodal blockade of conduction in A-fibers. 5. Temporal summation of the responses of spinothalamic tract cells was demonstrated both to brief trains of stimuli at 33 Hz and to single stimuli repeated at 1- to 2-s intervals. The latter phenomenon is often called "windup." 6. The responses of several spinothalamic tract cells to noxious heat pulses could still be elicited during anodal blockade of conduction in A-fibers. Similarly, it was possible to demonstrate an excitatory action of noxious mechanical stimuli despite interference with conduction in A-fibers by anodal current. 7. The cells investigated were located either in the marginal zone or in the layers of the dorsal horn equivalent to Rexed's laminae IV-VI in the cat. The cells were generally activated antidromically from the caudal part of the ventral posterior lateral nucleus of the thalamus.

The peptides substance P (SP), methionine-enkephalin (M-ENK), leucine-enkephalin (L-ENK), and cholecystokinin (CCK) were released iontophoretically near spinothalamic tract (STT) cells in anesthetized monkeys and STT-like cells in decorticate, spinalized monkeys. Peptide effects were observed on background discharges, firing induced by release of glutamate, and activity evoked by pinching the skin. SP could have any of several actions on STT cells, including excitation, inhibition, or biphasic effects. Multiple effects often resulted while recording from an individual cell when the dose or the electrode position was changed. M-ENK and L-ENK generally inhibited STT cells, and in some cases it was possible to demonstrate a reversal of the inhibition by naloxone. CCK also caused an inhibition that was additive with that produced by L-ENK. The multiple actions of SP on STT cells suggests the possibility that there may be more than one type of SP receptor on STT cells, although alternative explanations should be considered. Inhibition of STT cells by M- and L-ENK is consistent with the known analgesic action of opiates through spinal cord mechanisms. CCK has an action on STT cells similar to that of the enkephalins.