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Inhibition of cardiopulmonary input to thoracic spinothalamic tract cells by stimulation of the subcoeruleus-parabrachial region in the primate.

Effects of electrically stimulating the subcoeruleus-parabrachial (SC-PB) region on 31 spinothalamic tract neurons which receive excitatory input from cardiopulmonary sympathetic afferent fibers were studied in 21 monkeys anesthetized with chloralose. A conditioning stimulus to the SC-PB region inhibited the activity of 5 cells responding to the test stimulus applied to sympathetic afferent fibers. At a conditioning-test interval of 10 ms, test responses were maximally reduced to 47 +/- 6% of the control. Inhibitory effects were present at conditioning-test intervals up to 150 ms. Excitatory effects of both A delta-and C-fiber sympathetic afferents were reduced by stimulation of the SC-PB region; however, C-fiber input was more powerfully inhibited. Intracardiac injection of the algesic agent bradykinin excited 8 of 12 spinothalamic tract neurons tested; the responding cells increased their activity from 12 +/- 13 to 31 +/- 8 impulses/s. SC-PB stimulation (212 +/- 45 microA) reduced the peak activity caused by bradykinin to 6 +/- 2 impulses/s. Aortic occlusion increased the discharge rate of 5 out of 8 neurons from 13 +/- 3 to 21 +/- 4 impulses/s. At the peak of the response of aortic occlusion, SC-PB stimulation (238 +/- 20 microA) decreased neuron activity to 3 +/- 0 impulses/s. Effective sites for inhibition of spinothalamic tract cell activity were located in the lateral and medial parabrachial nuclei and the nucleus subcoeruleus. This study demonstrates that stimulation of the dorsolateral pons can inhibit the responses of upper thoracic spinothalamic tract neurons to cardiopulmonary sympathetic afferent input. Our laboratory previously has shown that stimulation of cardiopulmonary vagal afferents inhibits spinothalamic tract cells via supraspinal mechanisms. The SC-PB region may be a site activated by cardiac vagal afferents during ischemia and therefore, may be involved in the etiology of painless myocardial infarctions.

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Depression of primate spinothalamic tract neurons by iontophoretic application of 5-hydroxytryptamine.

The effects of iontophoretic applications of 5-hydroxytryptamine (5-HT) were tested upon primate spinothalamic tract neurons recorded extracellularly in the spinal cord of anesthetized monkeys. The activity of most high threshold and wide dynamic range spinothalamic tract cells was depressed. 5-HT also reduced the responses of the cells to glutamate pulses which by themselves had a powerful excitatory action. It is concluded that 5-HT has a depressant action upon the postsynaptic membranes of spinothalamic tract cells, although the action has a slow time course. The observations are consistent with, but by no means prove, the hypothesis that serotonergic pathways descending from the brain stem produce a postsynaptic inhibiton of spinothalamic tract neurons.

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Organization of the serotonergic innervation of spinal neurons in rats--I. Neuropeptide coexistence in varicosities innervating some spinothalamic tract neurons but not in those innervating postsynaptic dorsal column neurons.

Previous studies have suggested that peptides such as substance P and thyrotropin-releasing hormone coexist with serotonin in the same varicosities in the ventral horn and intermediate gray of the spinal cord in rat. However, coexistence of these peptides with serotonin is rare in fibers in the superficial dorsal horn. Since it has been proposed that serotonergic fibers in the superficial dorsal horn act to modulate nociception, it was hypothesized that the serotonergic neurons that contain neither substance P nor thyrotropin-releasing hormone might constitute a specifically antinociceptive subset of serotonergic neurons. This being the case, it would be expected that different types of serotonergic neurons innervate nociceptive and non-nociceptive spinal neurons. In order to test this hypothesis, a group of cells that include nociceptive neurons (spinothalamic tract neurons) and a group of predominantly non-nociceptive neurons (postsynaptic dorsal column neurons) in the spinal cord of rat were retrogradely labeled. Sections of the spinal cord containing retrogradely labeled spinothalamic tract or postsynaptic dorsal column neurons were stained for serotonin and either substance P or thyrotropin-releasing hormone using two-color immunohistochemistry. A retrogradely labeled cell was classified as "apposed" if there was no discernible distance between an immunohistochemically labeled varicosity and the cell. Eighty per cent of spinothalamic tract and 83% of postsynaptic dorsal column profiles were apposed by serotonin-immunoreactive varicosities in the spinal cord. Thirty-one per cent of the spinothalamic tract profiles that were apposed by serotonergic varicosities were apposed by serotonergic varicosities that were also stained for thyrotropin-releasing hormone. The distribution of the latter spinothalamic neurons was similar to that reported for spinothalamic tract neurons responsive to joint movement. In addition, at least 63% of the spinothalamic tract profiles which were apposed by serotonergic varicosities were apposed by "serotonin-only" varicosities, including most spinothalamic tract neurons in the marginal zone, suggesting that at least some "serotonin-only" neurons are antinociceptive. However, contrary to the hypothesis, at least 94% of the postsynaptic dorsal column profiles apposed by serotonergic varicosities were apposed by "serotonin-only" varicosities. These findings suggest that there may be a relationship between the sensory modality to which a spinal neuron responds and the type of serotonergic innervation it receives. However, it appears that "serotonin-only" neurons may not constitute a specifically antinociceptive category of serotonergic neurons.

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Static and dynamic responses of spinothalamic tract neurons to mechanical stimuli.

The activity of primate spinothalamic tract neurons was investigated. Units were identified by antidromic activation from the diencephalon. Most had a spontaneous discharge. The fastest spontaneous discharge rates were from neurons activated by receptors in muscles or joints. However, such activity could be decreased by repositioning the hindlimb. Spontaneous activity was also altered by changes in anesthetic level. Time-interval histograms demonstrated the patterns of spontaneous discharge. Many units could be excited by noxious stimulation. Graded step displacements of the skin often evoked a slowly adapting discharge which was a function of pressure (or displacements above a threshold of some hundreds of microns). Responses continued to increase as pressures became noxious. Rapidly adapting responses of hair-activated and low-threshold spinothalamic tract neurons were tested with ramp stimuli and found to signal acceleration (or a higher derivative of position), velocity, or a combination of these. Responses to stimulus acceleration were prominent when hairs were displaced, while responses to stimulus velocity were seen with displacement of the skin. Possible receptor types which might account for the observations are discussed.

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The primate dorsal spinothalamic tract: evidence for a specific termination in the posterior nuclei (Po/SG) of the thalamus.

The spinothalamic tract in primates and other mammals arises primarily from cells in lamina I of the dorsal horn, from lamina V cells and to a lesser extent from other laminae. Most of the neurons of lamina I respond only to noxious mechanical or thermal stimuli. Spinothalamic tract (STT) cells of lamina V tend to respond to both innocuous and noxious stimuli. Recent studies have suggested that the classical STT in the anterolateral quadrant (ALQ) contains primarily the axons of lamina V cells and that the axons of lamina I cells travel more dorsally in the dorsolateral quadrant (DLQ) to constitute the dorsal spinothalamic tract (DSTT). Using the anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) injected into the spinal cord in conjunction with a contralateral anterolateral cordotomy, we have found there is a substantial projection of the DSTT to the posterior nuclei of the caudal-ventral thalamus, designated Po/SG. This projection is almost entirely abolished when the lesion includes the area of spinal cord white matter at the level of the denticulate ligament. Larger lesions that destroy the ALQ and much of the lateral column white matter, but that spare the dorsolateral column white matter in the region of the corticospinal tract, abolish all transport of WGA-HRP to the thalamus. We conclude that the spinothalamic pathway in the non-human primate encompasses a continuous fiber bundle that extends dorsally to include the region of lateral column white matter opposite the denticulate ligament and that the more dorsal aspect of this pathway projects primarily to Po/SG of thalamus.

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Observations on the synaptology of intracellularly injected spinothalamic tract neurons in the cat.

Single spinothalamic tract cells in the deep lumbar group have been injected with horseradish peroxidase and their dendritic trees examined on the electron microscope. Large dendrites are surrounded by rosettes of from 5 to 12 synaptic terminals. Most terminals contain round vesicles but some terminals contain flattened clear vesicles and others contain membraneous tubes or cisterns. Large (mean diameter 100 nm) round, dense-core vesicles are found in both terminals containing clear round vesicles and terminals containing flattened vesicles. As yet none of those terminals on STT cell dendrites have been found participating in axo-axonic synapses, suggesting that presynaptic inhibition or facilitation plays no role in modulating the responses of these cells to presynaptic activity.

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Medial, intralaminar, and lateral terminations of lumbar spinothalamic tract neurons: a fluorescent double-label study.

A dorsolateral spinothalamic tract (DSTT), consisting primarily of lamina I neurons, was confirmed in the cat lumbar spinal cord by the use of thalamic injections of fluorescent dyes combined with selective thoracic spinal cord lesions. In addition, collateralization of spinothalamic tract (STT) terminations to medial, lateral, and intralaminar thalamic regions was investigated by injections of two different fluorescent dyes into pairs of these regions. The results of this study indicate that less than 15% of cat lumbar STT neurons collateralize to more than one of the thalamic regions evaluated. Lumbar lamina I cells project to the lateral and to the medial thalamus (13% collateralize to these two regions) and have only a scant projection to the intralaminar thalamus. Lumbar laminae IV-VI STT cells are very few in cat and demonstrate almost no collateralization to multiple thalamic areas. Neurons of laminae VII-X project equally to the three thalamic regions evaluated, and approximately 10-14% of cells from this laminar group collateralize to any two of the thalamic sites evaluated.

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Effects of mechanical and chemical stimulation of fine muscle afferents upon primate spinothalamic tract cells.

1. Injections of algesic chemicals were made into the arterial circulation of the triceps surae muscles in anaesthetized monkeys. 2. The responses of a sample of primary muscle afferents suggest that what is known about the activation of muscle afferents in the cat by algesic agents applies also to the monkey. One exception to this is the activation of many group I afferents by KCl in the monkey, but not in the cat. 3. Many spinothalamic tract cells were powerfully excited by the intra-arterial injection of algesic chemicals (bradykinin, 5-hydroxytryptamine (5-HT), KCl) in preparations in which the hind limb was denervated except for the nerves to the triceps surae muscles. The excitatory action of bradykinin had a slower time course than did that of 5-HT or KCl. 4. A number of the spinothalamic tract cells which failed to respond to chemical activation of muscle afferents were located in lamina I of the spinal cord. 5. Repeated injections of bradykinin produced similar responses, whereas the effects of 5-HT injections showed marked tachyphylaxis. 6. No evidence was obtained that activation of muscle spindle afferents by succinylcholine injections resulted in the excitation of spinothalamic tract neurones in the population sampled. 7. Injections of hypertonic NaCl into muscle or tendon produced a prolonged excitation of many spinothalamic tract cells. 8. It is concluded that a substantial proportion of primate spinothalamic tract cells receive a convergent input from cutaneous and muscle receptors. The muscle receptors involved appear to include primary afferents of group III and IV calibre. The possibility is suggested that such cells could play a role in the production of poorly localized pain.

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Evidence for glutamate as a neurotransmitter in spinothalamic tract terminals in the posterior region of owl monkeys.

Previous studies have suggested that glutamate is a neurotransmitter in ascending somatosensory pathways to the thalamus. The present study examined with quantitative immunohistochemical methods the presence of glutamate in spinothalamic tract terminals of owl monkeys (Aotus trivirgatus). Such terminals in the posterior region, in which a nucleus was recently identified as a specific pain and temperature relay in macaques and humans, were labeled by anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase, injected into the spinal dorsal horn. Glutamate-like immunoreactivity was demonstrated with a postembedding immunogold procedure using a well-characterized glutamate antiserum. Quantitative analysis of the immunogold labeling demonstrated that the spinothalamic tract terminals contained more than twice the tissue average of glutamate-like immunoreactivity. Enrichment of glutamate-like immunoreactivity was also found in terminals of presumed cortical origin. Presynaptic dendrites, cell bodies and non-vesicle-containing dendrites displayed low levels of glutamate-like immunoreactivity. A strong positive correlation (r = 0.69; P < 0.0001) was found between the density of synaptic vesicles and the density of gold particles in spinothalamic tract terminals, in contrast to a weak negative relationship (r = -0.28; P = 0.089) present in GABAergic presynaptic dendrites. These data provide strong evidence that the gold labeling in the spinothalamic tract terminals represents transmitter labeling, implying that glutamate is a neurotransmitter for ascending nociceptive and thermoreceptive information in primates.

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The effects of SDZ NKT 343, a potent NK1 receptor antagonist, on cutaneous responses of primate spinothalamic tract neurones sensitized by intradermal capsaicin injection.

Substance P, acting through neurokinin I receptors, is involved in the processing of nociceptive information in the spinal cord. Sensitization of spinothalamic tract neurons occurs to low-intensity stimuli following capsaicin injection. The current study tested the effects of the novel neurokinin I receptor antagonist, SDZ NKT 343, on the sensitization of spinothalamic tract cells by capsaicin in monkeys. Spinothalamic tract cells from the lumbar enlargement with receptive fields in the hindpaw were isolated and recorded before and after intradermal injection of capsaicin. The background activity and responses to brushing, pressing and pinching the skin were assessed. Thirty minutes after capsaicin injection there was an increase in background activity and responses to brush and pressure applied to the receptive field. Infusion of SDZ NKT 343 (for 30-45 min) significantly reversed the increased response to brushing without affecting the increased background activity or the increased response to pressure. Thus, blockade of neurokinin 1 receptors reduces the sensitized responses to innocuous mechanical stimuli but not to noxious mechanical stimuli.

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Response characterstics of spinothalamic tract neurons that project to the posterior thalamus in rats.

A sizeable number of spinothalamic tract axons terminate in the posterior thalamus. The functional roles and precise areas of termination of these axons have been a subject of recent controversy. The goals of this study were to identify spinothalamic tract neurons (STT) within the cervical enlargement that project to this area, characterize their responses to mechanical and thermal stimulation of their receptive fields, and use microantidromic tracking methods to determine the nuclei in which their axons terminate. Forty-seven neurons were antidromically activated using low-amplitude (< or =30 microA) current pulses in the contralateral posterior thalamus. The 51 points at which antidromic activation thresholds were lowest were surrounded by ineffective tracks indicating that the surrounded axons terminated within the posterior thalamus. The areas of termination were located primarily in the posterior triangular, medial geniculate, posterior and posterior intralaminar, and suprageniculate nuclei. Recording points were located in the superficial and deep dorsal horn. The mean antidromic conduction velocity was 6.4 m/s, a conduction velocity slower than that of other projections to the thalamus or hypothalamus in rats. Cutaneous receptive fields appeared to be smaller than those of neurons projecting to other areas of the thalamus or to the hypothalamus. Each of the examined neurons responded exclusively or preferentially to noxious stimuli. These findings indicate that the STT carries nociceptive information to several target nuclei within the posterior thalamus. We discuss the evidence that this projection provides nociceptive information that plays an important role in fear conditioning.

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Nuclei in which functionally identified spinothalamic tract neurons terminate.

The approximate level of termination of the axons of individual, functionally characterized spinothalamic tract neurons within the monkey thalmus was mapped by antidromic activation using a monopolar electrode which was moved in a systematic grid of tracks through the thalamus. The course of individual axons could be followed through several thalamic levels, and in a few cases branches to both the VPL nucleus and to the intralaminar nuclei were demonstrated. Most of the axons studied, however, projected just to the VPLc or VPLo nuclei. The spinothalamic tract cells that projected to the VPLc nucleus included representative of all known functional categories: low threshold, wide dynamic range, high threshold and "deep." It is speculated that these different classes of spinothalamic projections could make contributions to such sensory modalities as touch, proprioception and pain.

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Properties of deep spinothalamic tract cells in the rat, with special reference to ventromedial zone of lumbar dorsal horn.

Spinothalamic tract cells lying at the base of the dorsal horn or in deeper areas were identified in the rat at the lumbar spinal cord level by injecting horseradish peroxidase or stimulating posterior thalamic areas. Two groups of neurons were delineated; each constituted a homogeneous population of cells in terms of electrophysiological properties. Ventromedial dorsal horn cells lay at the base of the dorsal horn in its most medial aspect. They constitute a densely packed formation, which in the rat's ascending pathway system is restricted to the spinothalamic tract. Their main characteristics were a) ongoing activity, which consisted of small groups of spikes occurring at regular intervals, with a maximal discharge during ankle extension; b) unilateral receptive fields, which were restricted to the distal parts of the limb and involved both proprioceptive (ankle, joint digits) and exteroceptive (foot skin) structures; c) input of innocuous origin (midrange articular movement, touch, pressure) that was excitatory and input of noxious cutaneous origin (radiant heat) that was inhibitory; the same areas of foot skin were thus potentially either excitatory or inhibitory, depending on the nature of the stimulus applied; d) ankle flexion could differentially modulate both ongoing activity and excitatory responses from distal parts of the limb, inhibiting the former and potentiating the latter. In consequence, the ability of these cells to be driven by both proprioceptive and cutaneous inputs from limb extremities as well as by interactions of these inputs would appear to be very favorable for informing the central nervous system about limb position in both passive postural changes and the step cycle. It is suggested that they supply the thalamus with integrated information about locomotion. Lamina VII cells also constituted a subpopulation of neurons with very homogeneous electrophysiological properties. They were characterized by widespread inhibitory receptive fields, possibly spanning both hindlimbs and the ipsilateral forelimb. Inhibition was most effective when the stimulus (pressure, pinch) was intense and applied to proximal parts of the hindlimb. Ongoing activity consisted of spikes set at regular intervals and sometimes related to midrange movements of the knee. Although the significance of the widespread inhibitory receptive fields remains unclear, it has been suggested that these neurons are involved in the transmission of proprioceptive information.(ABSTRACT TRUNCATED AT 400 WORDS)

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The effect of trans-ACPD, a metabotropic excitatory amino acid receptor agonist, on the responses of primate spinothalamic tract neurons.

The responses of primate spinothalamic tract (STT) neurons to innocuous and noxious mechanical stimuli applied to the skin can be enhanced for more than an hour following prolonged noxious stimulation. This increased responsiveness is thought to reflect sensitization of dorsal horn neurons and may help account for secondary hyperalgesia and mechanical allodynia. The proposal that central sensitization is due to the activation of second messenger system was tested in this study by examining the effect of trans-ACPD (trans-D,L-1-amino-1,3-cyclopentanedicarboxylic acid), an agonist of metabotropic excitatory amino acid (EAA) receptors, introduced into the dorsal horn by microdialysis. A low dose of trans-ACPD resulted in an increase in the responses of STT cells to an innocuous mechanical stimulus (BRUSH), but no increase in the responses to noxious mechanical and thermal stimuli or in the excitation produced by iontophoretically applied EAAs. A high dose of trans-ACPD caused a transient increase in background activity, but no change in the responsiveness of spinothalamic cells to any of the test stimuli. It is concluded that low doses of trans-ACPD can selectively enhance transmission through interneuronal pathways mediating tactile inputs to spinothalamic cells.

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Identification of spinothalamic tract cells in fresh, unfixed rat spinal cord.

Diamidino yellow dihydrochloride (DY . 2HCl) can reliably label spinothalamic tract cells both in the perfused, fixed and in the fresh, unfixed rat spinal cord. The major advantages of DY . 2HCl as a retrograde marker are that it leaks from the cells very slowly and can be conveniently identified in unfixed neurons by fluorescence microscopy. DY . 2HCl will be a useful marker for identification of spinothalamic tract cells that are to be studied in vitro.

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Prolonged inhibition of primate spinothalamic tract cells by peripheral nerve stimulation.

Inhibition of spinothalamic tract (STT) cells was produced by repetitive peripheral nerve conditioning stimulation with high intensity and low frequency pulses. Identified STT cells were recorded from the lumbosacral spinal cord of intact, anesthetized monkeys. In addition, presumed STT cells were recorded from both unanesthetized, decerebrated and decerebrated, spinalized monkeys. These cells were identified by antidromically activating them from the contralateral ventral lateral funiculus of the cervical spinal cord. Both C fiber activity evoked by electrical stimulation of the sural nerve and activity evoked by noxious heat were greatly inhibited by repetitive conditioning stimuli applied either to the common peroneal or tibial nerve with a strong enough intensity for activation of C fibers at 2 Hz for 15 min. The inhibition was maintained during the period of conditioning stimulation and often outlasted stimulation by 20-30 min. The inhibition of cells produced by peripheral nerve stimulation was observed in decerebrate and spinalized animals as well as in intact anesthetized monkeys, although the mean recovery time in the decerebrate group was faster. This indicates that anesthetics did not interfere with the inhibitory mechanism. Furthermore, the presence of inhibition in spinalized animals means the inhibition must depend in part on spinal cord neuronal circuitry. Intravenous injection of naloxone produced a significant but small reduction of the recovery phase of the inhibition. No pharmacological agent was found that substantially interfered with the powerful inhibition produced during peripheral conditioning stimuli. The experimental animal model used in these experiments seems appropriate for studying the mechanisms of analgesia produced by peripheral nerve stimulation.

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Glutamate-immunoreactive terminals synapse on primate spinothalamic tract cells.

Glutamate has been shown to excite spinothalamic tract (STT) neurons and has been localized to primary afferent neurons, spinal cord projection neurons, and interneurons in the spinal cord dorsal horn. The likelihood that glutamate-immunoreactive (GLU-IR) terminals directly innervate STT neurons was investigated. For these studies three lamina IV or V STT cells in the lumbar spinal cords of three monkeys (Macaca fascicularis) were identified electrophysiologically and characterized. Two were identified as high threshold neurons and one as a wide dynamic range neuron. Following intracellular injection of the cells with HRP and reaction to give the cells a Golgi-like appearance, the tissues were processed for electron microscopy. Postembedding immunogold methods with antibodies specific for glutamate were used to identify GLU-IR terminals apposing the somata and dendrites of the STT neurons, including dendrites that extended into laminae IV and III. The GLU-IR terminals were numerous and constituted a mean of 46% of the population counted that appose the STT soma and 50% of the profiles apposing the dendrites. Fifty-four percent of the somatic and 50% of the dendritic surface length was contacted by GLU-IR terminals. Most terminals contained round clear vesicles and some contained a variable number of large dense core vesicles. For one of the three cells examined it was determined that 45% of the terminals apposing the soma were GLU-IR and 30% of the terminals were gamma aminobutyric acid-immunoreactive (GABA-IR). In an additional monkey, a lamina I cell retrogradely labeled from the ventral posterolateral nucleus of the thalamus was found to be ensheathed in glial processes.(ABSTRACT TRUNCATED AT 250 WORDS)

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Neurogenic hyperalgesia: central neural correlates in responses of spinothalamic tract neurons.

1. The contribution of activity in spinothalamic tract (STT) neurons to the pain and neurogenic hyperalgesia produced by an intradermal injection of 100 micrograms of capsaicin was investigated. Electrophysiological responses of identified STT neurons recorded in anesthetized monkeys were compared with psychophysical measurements of pain and hyperalgesia obtained in humans using identical stimuli. 2. Magnitude estimates of pain in humans were obtained after an injection of capsaicin or the vehicle. Capsaicin produced immediate burning pain that was most intense within 15 s after injection and then declined over the next 10-30 min. The vehicle produced no pain. 3. Cutaneous hyperalgesia to gentle stroking (allodynia) and also hyperalgesia to punctate stimulation developed in a wide area surrounding the capsaicin injection. Within this area, magnitude estimates of pain produced by a punctate stimulus (von Frey type with force of 225 mN) increased over preinjection values by an average of sixfold at test sites, 1, 2, and 3 cm away from the injection site. At the capsaicin injection site, magnitude estimates of pain in response to punctate simulation typically remained the same or were decreased. 4. After capsaicin, but not vehicle, the mean heat pain thresholds were lowered from approximately 45 degrees C before injection to 34 degrees C after, but only in the immediate vicinity of the injection site. At a site located 2 cm away, the thresholds were not significantly altered. Similarly, magnitude estimates of pain produced by suprathreshold heat stimuli were increased after capsaicin only at the injection site. 5. STT neurons were classified as high-threshold (HT) or wide-dynamic-range (WDR) cells according to responses evoked by graded cutaneous mechanical stimulation. An intradermal injection of capsaicin excited 4 of 7 HT cells and 10 of 12 WDR cells. The discharge rates of STT neurons correlated in time course with the magnitude estimates of pain in humans. The correlation was considerably better for WDR than for HT neurons, suggesting a predominant contribution of WDR neurons to the pain from capsaicin. 6. Capsaicin significantly increased the responses of HT neurons (9-fold) and the responses of WDR neurons (2-fold) to stroking the skin within the receptive field. Similar increases in responses to a standard punctate stimulus were observed at test sites, 1, 2, and 3 cm away from the injection site. After injection of vehicle, the responses to punctate stimulation increased by a mean of only 1.2- and 1.4-fold for HT and WDR neurons, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

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