Primate Spinothalamic Neurons Research Articles

Relief of itch by scratching: state-dependent inhibition of primate spinothalamic tract neurons

Itch is relieved by scratching, but the neural mechanisms that are responsible for this are unknown. Spinothalamic tract (STT) neurons respond to itch-producing agents and transmit pruritic information to the brain. We observed that scratching the cutaneous receptive field of primate STT neurons produced inhibition during histamine-evoked activity but not during spontaneous activity or activity evoked by a painful stimulus, suggesting that scratching inhibits the transmission of itch in the spinal cord in a state-dependent manner.

Gene therapy for the management of pain: part II: molecular targets.

TREATMENT of chronic pain, particularly of neuropathic etiology, is extremely difficult and resistant to many available pharmacologic therapies. Current analgesic agents may be limited with regard to analgesic efficacy or side effects. Newer and experimental pharmacologic agents may also have significant limitations. By targeting a specific receptor or other specific protein targets, a gene therapy approach to the treatment of pain may provide greater analgesic efficacy without the limitations associated with current pharmacotherapy. Advances in the field of gene therapy, along with significant increases in our understanding of the neurobiology of nociception and knowledge of the fundamental genetic structure of many nociceptive targets, have made gene therapy for the management of pain a conceivable reality. In part I of this review, we introduced the basic concepts of gene therapy with an emphasis on the available tools (e.g., viral vectors and antisense oligonucleotides) and strategies for upregulating antinociceptive or downregulating pronociceptive targets. In part II, we summarize current knowledge regarding the nociceptive role, molecular biology, and antisense and knockout data of several novel nociceptive targets for gene therapy. We base our selection of the targets included in this review on the three aforementioned criteria. The targets selected are the best characterized and, in our opinion, most likely amenable to the gene therapeutic approach. A simple but feasible strategy and potential gene therapy targets for the management of pain are summarized in figure 1. However, the list is admittedly incomplete, and the readers are referred to other recent reviews cited in part I of this review for a broader perspective on potential targets for the management of pain.

The effect of phorbol esters on the responses of primate spinothalamic neurons to mechanical and thermal stimuli

1. Sensitization of dorsal horn neurons is thought to play an important role in pain perception, secondary hyperalgesia, and allodynia. Recent experimental evidence suggests that the sensitization of dorsal horn neurons is induced by combined increased release of excitatory amino acids and peptides in the spinal cord dorsal horn from nociceptive primary afferents due to an injury-caused barrage of impulses. We tested the hypothesis that protein kinase C (PKC) is involved as a second messenger in this process of neuronal sensitization. To activate PKC, infusion of a phorbol ester [12-O-tetradecanoylphorbol-13-acetate (TPA)] into the dorsal horn through a microdialysis fiber was used. During TPA infusion the background activity of spinothalamic (STT) neurons increased substantially. After TPA application, while the background activity of the STT neurons was still increased, the responses evoked by either innocuous or noxious mechanical stimulation of the cutaneous receptive field did not change from the control level. However, 1 h after TPA administration the background activity returned to the control level and responses to innocuous mechanical stimuli were significantly elevated. The responses of STT cells to noxious heat and noxious mechanical stimuli did not change significantly after TPA administration. When a phorbol ester that does not activate PKC was applied (alpha-TPA), no significant changes in background or evoked activity of STT cells were observed. Our results provide evidence that PKC may play an important role in the process of sensitization of dorsal horn neurons to innocuous mechanical stimuli.

Chronic effects of topical application of capsaicin to the sciatic nerve on responses of primate spinothalamic neurons

The responses of 144 spinothalamic tract (STT) cells were recorded in 15 anesthetized macaque monkeys ( Macaco fascicularis). Three to 4 weeks prior to the acute experiment, the sciatic nerve was surgically exposed on one or both sides so that capsaicin or vehicle could be applied. Responses of STT cells recorded in 3 experimental groups were compared: untreated (21 cells), vehicle-treated (40 cells), and capsaicin-treated (83 cells). The background activity of cells in the vehicle- and capsaicin-treated groups was the same as in the untreated group (that is, cells on the side contralateral to surgery). Responses to innocuous (BRUSH) and noxious (PINCH) mechanical stimuli were unchanged by vehicle or by capsaicin treatment. However, responses to other noxious (PRESSURE and SQUEEZE) mechanical stimuli were significantly increased in the vehicle-treated group. Compared with a large reference population, all experimental groups showed a significant increase in overall responsiveness to mechanical stimuli (as determined by cluster analysis), greatest in the vehicle-treated group. Responses to noxious heat stimuli were significantly reduced in the capsaicin-treated group for 45°C and 47°C stimuli. Volleys in A fibers, probably Aδ fibers, evoked prolonged responses in many STT cells of all treatment groups. Electron microscopic counts of axons in the sciatic nerves of animals treated with capsaicin showed a reduced number of C fibers but no appreciable loss of myelinated axons. This loss of unmyelinated sensory fibers was presumably responsible for the reduction in the responses of the STT cells to noxious heat stimuli. Increased responses to some noxious mechanical stimuli and to A fiber volleys may have been the consequence of several factors, including surgical manipulation, a chemical action of vehicle and a contralateral action of capsaicin treatment.

Bowditch Lecture. Renal afferent inputs to ascending spinal pathways.

Studies of renal afferent fibers and their functions have continued since the work of Pines in 1959 (Fiziol. Zh. SSSR Im. I M Sechenova 45: 1339-1347, 1959). The kidney contains mechanoreceptors and chemoreceptors that appear to have two major functions. First, renal mechano- and chemoreceptors evoke a variety of renorenal reflexes, while more global cardiovascular reflexes are primarily evoked by renal mechanoreceptors. A second function of renal afferent fibers is to cause the pain of renal disease. Recent studies suggest that renal afferent fibers may also regulate secretion of vasopressin from the pituitary gland. Substantial evidence indicates that, although most renal afferent fibers enter the spinal cord, their functions depend to a large extent on supraspinal circuitry. Thus our research has focused on defining characteristics of spinal neurons that relay renal information to the brain. In the cat, neurons in the L2-T11 segments with excitatory responses to renal A delta and C fiber input project to the medial medullary reticular formation and to the caudal and rostral ventrolateral medulla. Renal afferent information reaches these cells by way of the least splanchnic nerve and by way of more than one dorsal root. In the monkey spinothalamic neurons in the L3-T10 segments respond to renal nerve stimulation. Excitatory responses predominate, but inhibitory responses occur in L2 and L3. These cells also respond to renal A delta and C fibers. Stimulation of renal mechanoreceptors by occlusion of the ureteropelvic junction or renal vein excites feline spinoreticular neurons. Graded increases in renal vein pressure produce graded increases in cell responses. Activation of renal chemoreceptors increases activity of spinal interneurons. Within the L2-T11 segments, cells responding to ureteral occlusion are located caudally, cells with responses to renal artery occlusion are located rostrally, and cells responding to renal vein occlusion are located in between. The differential locations of cells with these inputs suggests the existence of a coding mechanism for different renal receptor populations. Distention of the renal pelvis is a potent stimulator of primate spinothalamic neurons. These neurons encode renal pelvic pressures in the noxious range and appear to be important in mechanisms of renal pain.

Enhancement of spinothalamic neuron responses to chemical and mechanical stimuli following combined micro-iontophoretic application of n-methyl- d-aspartic acid and substance P

A role for sensitization of nociceptors in the generation of primary hyperalgesia is well documented. More recent work has begun to define a role of an increased excitability of neurons within the spinal cord in the generation of secondary hyperalgesia. The present study demonstrates increased responses of primate spinothalamic neurons following co-administration of n-methyl- d-aspartic acid (NMDA) and substance P (SP) by micro-iontophoresis. Wide dynamic range and high threshold STT neurons in laminae I-VI showed an increased frequency of discharges following application of NMDA which was characterized by a slow onset to peak discharge rate and a slow return to background levels of discharge. Combined application of NMDA with SP resulted in an enhancement of responses to NMDA that often long outlasted the administration of SP. This increase in response of the cells to NMDA was not produced by repeated application of NMDA alone or following combined application of NMDA with an SP analog. NMDA responses were reduced or prevented in all cases by co-application of an NMDA-receptor antagonist. Finally, long-lasting potentiation of NMDA responses by SP was paralleled by enhanced responses to mechanical stimulation of skin. It is proposed that a mechanism involving the combined synaptic release of excitatory amino acids and peptides leads to secondary hyperalgesia.

Modification of the responses of primate spinothalamic neurons to mechanical stimulation by excitatory amino acids and an N-methyl- d-aspartate antagonist

Excitatory amino acids (EAAs) are likely to play a key role in sensory transmission in the spinal cord. In the present study, the microiontophoresis technique was used to investigate the effects of l-glutamate (GLUT), N-methyl- d-aspartate (NMDA), and quisqualate (QUIS), as well as an NMDA receptor antagonist, AP-7, on the discharges evoked in nociceptive primate spinothalamic tract (STT) neurons by mechanical stimulation of the skin. Responses to innocuous brushing of the skin were facilitated by GLUT and NMDA (and in some neurons by QUIS) and sometimes reduced by AP-7. GLUT also facilitated the responses to noxious mechanical stimuli. The results are consistent with anatomical evidence for the presence of synapses that contain EAAs on primate STT cells and with the proposal that the co-release of EAAs and neuropeptides may contribute to hyperalgesia.

Electrophysiological characteristics of primate spinothalamic neurons with renal and somatic inputs.

1. Spinothalamic tract (STT) neurons in the T10-L3 segments were studied for responses to renal and somatic stimuli. A total of 90 neurons was studied in 25 alpha-chloralose anesthetized monkeys (Macaca fascicularis). All neurons were antidromically activated from the ventral posterior lateral nucleus of the thalamus. 2. Sixty-two cells were excited by renal nerve stimulation and six inhibited. Probability of locating cells with renal input was greatest in T11-L1. Cells were located in laminae I and IV-VII; however, most were located in laminae V-VII. Antidromic latencies averaged 4.61 +/- 0.32 (SE) ms, whereas antidromic conduction velocities averaged 43.23 +/- 9.03 m/s. 3. Cells with excitatory renal input received A delta input only (36 cells) or A delta- and C-fiber inputs (26 cells). Stimulation of A delta renal afferent fibers evoked bursts of 1-10 spikes/stimulus [mean 3.6 +/- 0.9 spikes/stimulus] with onset latencies of 10.7 +/- 0.5 ms. Stimulation of C-fibers evoked 1.3 +/- 0.5 spikes/stimulus with onset latencies of 61.7 +/- 11.1 ms. Magnitude of responses to A delta-fiber stimulation was greatest in T12 and decreased both rostrally and caudally. Inhibitory responses to renal nerve stimulation required activation of renal C-fibers. 4. All cells that responded to stimulation of renal afferent fibers received convergent inputs from somatic structures. Forty-four cells were classified as wide dynamic range, 10 were high threshold, 12 were high-threshold cells with inhibitory input from hair, 2 were deep, and 2 were low threshold. Somatic receptive fields were large and located on the flank and abdomen and/or the upper hindlimb. Fourteen cells had inhibitory receptive fields located on the contralateral hindlimb or one of the forearms. 5. It is concluded that T11-L1 STT cells in the monkey respond reliably to renal nerve stimulation. Thoracolumbar STT cells may thus play a role in pain that results from renal disease. The locations of the somatic receptive fields of the cells suggest that they are responsible for the referral of renal pain to the flank and abdomen.

Natural groupings of primate spinothalamic neurons based on cutaneous stimulation. Physiological and anatomical features.

1. Two hundred and twenty-one spinothalamic tract (STT) neurons in the lumbar spinal cord of anesthetized monkeys were studied. The majority of the recordings were in laminae IV-VI. Thirteen of these neurons were intracellularly injected with horseradish peroxidase and histologically reconstructed. 2. A standard series of four mechanical cutaneous stimuli, which ranged in intensity from innocuous brushing to tissue-damaging pinching, were used to test the mechanical responsiveness of STT neurons. The mean alterations in discharge rate produced by these test stimuli when delivered to a neuron's excitatory receptive field were used as response measures. 3. Univariate and bivariate analyses of these response measures failed to reveal natural groupings of STT neurons. To assess whether natural groupings dependent upon shared multivariate response patterns were present, a k-means cluster analysis of the responses was performed. 4. Because an assumption about the type of coding used by the STT system had to be made prior to clustering, two independent analyses were performed. One approach assumed a labeled line coding model; response magnitudes were determined within the context of the neuron under study (within-neuron analysis). The other approach assumed a population coding model; response magnitudes were determined within the context of the STT population (across-neuron analysis). 5. The within-neuron analysis suggested that the STT sample could be partitioned into four groups. The smallest group (n = 18, 8%) responded primarily to brushing but often had a convergent nociceptive input; this group was referred to as type I. A second group (n = 31, 14%) had strong responses to low-intensity stimuli, particularly pressure, and modestly larger responses to noxious stimuli; this group was referred to as type II. The clustering in these two groups was relatively weak, reflecting some heterogeneity in response pattern. 6. The largest within-neuron group (n = 108, 49%) was most responsive to noxious stimuli but had a saturating response function; because of their apparent role in coding intermediate intensity stimuli, this group was referred to as type III. The fourth group (n = 64, 29%) responded best to the most intense stimulus used; this group was referred to as type IV. 7. The across-neuron analysis also suggested that the STT sample could be partitioned into four groups. The largest group (n = 122, 55%) had relatively weak responses to all the cutaneous stimuli; this group was referred to as type A. 8. All of the remaining across-neuron groups had mean responses at or above the mean for all cutaneous stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

Temporal features of the responses of primate spinothalamic neurons to noxious thermal stimulation of hairy and glabrous skin.

Extracellular recordings were made from 81 primate spinothalamic (STT) neurons in the L7-S1 segments of the spinal cord. The majority of the sample was recorded from within laminae IV-V. The temporal features of the responses to noxious thermal stimulation of glabrous and hairy skin were studied in an attempt to determine whether natural groupings of STT neurons could be identified on the basis of response time course alone and whether these groups were skin type dependent. The relationship between these groups and those based on static response features (37) was also explored in an attempt to define more fully their potential functional roles. In most STT neurons, the thermally evoked responses typically appeared to have two response components, particularly at stimulus temperatures above 49 degrees C. The first response phase typically peaked within 1-12 s of stimulus onset and then adapted. The second phase slowly rose to a maximum, typically 15-30 s following stimulus onset. The existence of natural groupings of STT neurons based upon the characteristics of these two response components was assessed with a k-means cluster analysis. On the basis of the onset and early peak latencies, two well-defined short and long latency neuronal clusters were found in the responses evoked from both glabrous and hairy skin; these were referred to as the SP1 and LP1 classes, respectively. The glabrous and hairy skin SP1 classes did not differ significantly in either onset or early peak latency for stimuli of 47-55 degrees C. However, the hairy skin LP1 class had significantly shorter onset latencies than the glabrous skin LP1 class for stimuli of 49-53 degrees C, as well as shorter peak latencies for stimuli of 49 and 51 degrees C. The SP1 class constituted 62% of the hairy skin subset, whereas the LP1 class constituted 57% of the glabrous skin subset. A cluster analysis of the late-peak latencies also revealed two subgroups. In the responses evoked from both glabrous and hairy skin, the longer latency classes (LP2) constituted more than 80% of the samples. With one exception, no dependence upon the type of skin that was stimulated was found in the latencies of either the LP2 class or the shorter latency SP2 class. Prior conditioning of the skin with a 30-s thermal pulse of 51-55 degrees C led to a suppression of the early response phase and an enhancement of the late phase in nearly all cases examined (n = 11). This pattern was independent of skin type.(ABSTRACT TRUNCATED AT 400 WORDS)

Responses of primate spinothalamic neurons to noxious thermal stimulation of glabrous and hairy skin.

Extracellular recordings were made from 81 primate spinothalamic (STT) neurons in the L7-S1 segments of the spinal cord. The majority of the sample was recorded from within laminae IV-V. The responses of STT neurons to noxious thermal stimulation of glabrous and hairy skin were studied in an attempt to identify a neural substrate for the differences in thermal sensation evoked by noxious stimulation of these two types of skin. In addition, the responses to graded mechanical stimuli were examined for evidence of differential sensitivity. Thermal intensity-response functions were constructed from the alteration in the mean discharge rate produced by a 30-s thermal pulse of 43-55 degrees C. Generally, the functions derived from stimulation of both hairy and glabrous skin were either linear or positively accelerating. Deceleration in the response functions was occasionally observed above 53 degrees C. The population mean discharge rate derived from glabrous skin stimulation was significantly greater than that derived from hairy skin stimulation above 49 degrees C. Cluster analysis was used to assess whether the STT population could be partitioned into functionally relevant subgroups. No clustering was evident on the basis of the alteration in discharge rate during stimulation alone. Analysis of the alteration in mean discharge rate during and following thermal stimulation identified four groups; these were referred to as the Amnr, Bmnr, Cmnr, and Dmnr classes. The clustering was not dependent on differences in the responses evoked from hairy and glabrous skin. The mechanical and thermal sensitivities of each thermal class covaried. The capacity of the STT population to code the quality of noxious thermal stimuli, as judged by changes in the across-neuron discharge pattern, was assessed with a multidimensional scaling technique (MDS). The results suggest that the population discharge could be used to order stimuli correctly from 45 to 55 degrees C. Also, it was found that a substantial change in the population's discharge pattern occurred to stimuli between 47 and 49 degrees C when delivered to hairy skin. A similar alteration in the population's discharge pattern occurred to glabrous skin stimuli near 51 degrees C. These alterations in population behavior may underly the alterations in sensory quality in humans that occur in these temperature ranges when stimulating hairy and glabrous skin. The possible roles of the thermally and mechanically based classes in thermal intensity and quality coding were examined. Within the lower intensity ranges (less than 49-51 degrees C), the Cmnr and Dmnr classes appeared to be best suited to intensity coding.(ABSTRACT TRUNCATED AT 400 WORDS)

Classification of primate spinothalamic and somatosensory thalamic neurons based on cluster analysis.

Data analyzed in this study were derived from the responses of 128 spinothalamic tract (STT) cells and 110 thalamic neurons recorded in 75 anesthetized monkeys. A k-means cluster analysis, a nonhierarchical clustering technique, was performed using the relative magnitudes of responses to a graded series of innocuous and noxious mechanical stimuli applied to the receptive field. For comparison, a parallel analysis was performed based on definitions of low-threshold (LT), wide dynamic range (WDR), and high-threshold (HT) cells used by our laboratory. For 128 STT cells, a classification scheme with three clusters was found statistically to be the best. This yielded groups of 22, 57, and 49 cells in clusters 1, 2, and 3, respectively. Cluster 1 cells were activated best by low-intensity mechanical stimuli, whereas cluster 3 cells were activated primarily by nociceptive stimuli. Cluster 2 cells had intermediate characteristics. When the classification scheme based on the cluster analysis was compared with the classification of the same neurons as LT, WDR, and HT cells, cluster 1 cells were divided into LT and WDR cells, whereas cluster 2 and 3 cells included WDR and HT cells. For 110 thalamic neurons, a classification scheme with five clusters was found statistically to be the best. Clusters 1-5 contained 25, 34, 17, 10, and 24 cells, respectively. Response characteristics of cells in each group indicated a gradual change in sensitivity to higher intensities of peripheral input from cluster 1 to 5. When this classification scheme was compared with the classification scheme previously used by our laboratory, cluster 1 cells belonged to the LT group, clusters 2 and 3 split into LT and WDR cells, and clusters 4 and 5 included WDR and HT cells. It is concluded that a classification scheme based on a cluster analysis of the responses of neurons to standardized stimuli may provide an objective and functionally meaningful way to categorize somatosensory neurons.

Responses of primate T1-T5 spinothalamic neurons to gallbladder distension

Extracellular unit recordings were obtained from 44 spinothalamic tract (STT) neurons in the T1-T5 segments of 15 alpha-chloralose anesthesized monkeys (Macaca fascicularis). Each cell had a somatic receptive field in the left chest region and was excited by electrical stimulation of cardiopulmonary sympathetic afferent fibers. Gallbladder distension to pressures between 20 and 100 mmHg increased activity in 16 of 44 neurons. Responses usually consisted of bursts of activity associated with increased gallbladder pressure (phasic responses) followed by maintained activity during the distension (tonic responses). Magnitude of phasic responses was linearly related to the distending pressure and was consistently greater than magnitude of tonic responses. The gallbladder-responsive and nonresponsive groups included similar proportions of wide dynamic range, high threshold, and high-threshold inhibitory cells. Nine of 10 gallbladder-responsive cells and 11 of 21 gallbladder-nonresponsive cells increased their discharge rate after injection of 2 micrograms/kg bradykinin into left atrium. Activity of cells with gallbladder input increased from 14 +/- 4 to 33 +/- 4 spikes/s. Cells without gallbladder input increased their discharge rate to a significantly less degree (10 +/- 3-23 +/- 4 spikes/s). These results indicate that upper thoracic STT neurons may increase their activity during gallbladder distension. Convergence of afferent information from the chest and gallbladder may explain chest pain occurring during gallbladder disease. Furthermore the tendency of gallbladder-responsive cells to respond to bradykinin injections with a high rate of discharge could explain how this chest pain of gallbladder origin may closely mimic pain of angina pectoris.

Responses of primate spinothalamic neurons located in the sacral intermediomedial gray (stilling's nucleus) to proprioceptive input from the tail

Extracellular and intracellular recordings were obtained from 24 spinothalamic neurons located in the intermediomedial gray (Stilling's nucleus) in the S2 and S3 spinal segments of anesthetized adult monkeys ( Macaca fascicularis). Most units were spontaneously active. They lacked cutaneous receptive fields but could be excited by subcutaneous receptors. Bending the tail to one side of the animal's body axis excited cells located on the contralateral side of the cord and inhibited ipsilateral cells. The firing rate of each cell was a reproducible function of the angle of the portion of the tail distal to the innervated segment. Cells responded with a burst of spikes to electrical stimulation of low threshold ipsilateral primary afferent fibers in the homosegmental dorsal root. The latency of the underlying synaptic potential was 0.5–0.7 from the time of arrival of the afferent volley at the cord, indicating monosynaptic input. Low intensity stimulation of the contralateral homosegmental dorsal root inhibited background activity. The latency of the underlying inhibitory synaptic potential was 0.8–1.1 ms, suggesting crossed disynaptic inhibition. We conclude that sacral spinothalamic tract neurons located in the intermediomedial gray participate in signalling the spatial orientation of the animal's tail.

Convergence of cutaneous and pelvic visceral nociceptive inputs onto primate spinothalamic neurons

The responses of 66 primate spinothalamic neurons to natural stimulation the the urinary bladder and testicle were studied with extracellular recording techniques in order to elucidate the neural basis for referral of visceral pain. Thirty-eight out of 53 cells located at the thoraco-lumbar junction or in sacral segments responded to noxious cutaneous stimuli, and 84% of these also exhibited phasic and/or tonic excitatory responses to distension of the urinary bladder. Seventeen out of 20 of these units, all located at the thoraco-lumbar junction, were excited by compression of the ipsilateral testicle. The response was graded with the compressive force. Excitatory responses to noxious heat and an irritant chemical (KC1) applied to the exposed testicular surface were also observed. Twelve sacral units having inputs from deep receptor of the tail exhibited mixed excitatory and inhibitory responses to bladder distension. A further 2 cells located at the thoracolumbar junction responded only to cutaneous tactile stimuli, and 13 cells located at the lumbosacral enlargement were tonically inhibited by bladder distension. It is concluded that spinothalamic neurons that convey nociceptive input from the skin may also respond to noxious visceral stimuli. Such viscero-somatic convergence provides a neural substrate for the phenomenon of cutaneous referral of visceral pain.

Effects of peripherally and centrally administered serotonin on primate spinothalamic neurons.

Serotonin has actions at several different levels of the neural system responsible for nociception. When injected into the arterial circulation of a muscle, serotonin excites small myelinated and unmyelinated fibers supplying nociceptors (Mense & Schmidt, 1974; Fock & Mense, 1976; Mense, 1977). Serotonin is thus an algesic agent in terms of its peripheral action. By contrast, serotonin is thought to be one of the synaptic transmitters in the central nervous system pathways that mediate stimulation-produced analgesia (Akil & Mayer, 1972; Akil & Liebeskind, 1975; Yaksh, 1979; Yaksh & Wilson, 1979).

Postsynaptic inhibition of primate spinothalamic neurons by stimulation in nucleus raphe magnus

Postsynaptic inhibition of primate spinothalamic neurons by stimulation in nucleus raphe magnus

Responses of primate spinothalamic neurons to graded and to repeated noxious heat stimuli.

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.

Excitation of primate spinothalamic neurons by cutaneous C-fiber volleys.

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.

Effects of stimulation of sensorimotor cortex on primate spinothalamic neurons

Effects of stimulation of sensorimotor cortex on primate spinothalamic neurons