Chronic tooth pulp inflammation causes transient and persistent expression of Fos in dynorphin-rich regions of rat brainstem.

We have analyzed central Fos immunoreactivity (Fos-IR) brainstems of adult rats after three clinically relevant dental injuries: filled dentin (DF) cavities that cause mild pulp injury and heal within 1-2 weeks; open pulp exposures (PX) that cause gradual pulp loss and subsequent periodontal lesions; and filled pulp exposures (PXF). By 1 week after DF cavities, no Fos-IR remained except for sites such as lateral-ventral periolivary nucleus (LVPO) that had Fos-IR in all rats including controls. PX injury induced (1) a delayed transient expression of Fos at 1-2 weeks at three loci (ipsilateral neurons in dorsomedial nucleus oralis, paratrigeminal nucleus, and trigeminal tract), (2) persistent ipsilateral Fos for at least 4 weeks after injury in dynorphin (Dyn)-rich regions (rostral lateral solitary nucleus, periobex dorsal nucleus caudalis), and (3) late Fos-IR at 2-4 weeks (bilateral superficial cervical dorsal horn, contralateral dorsal nucleus caudalis, contralateral rostral lateral solitary nucleus). Rats with PXF injury were examined at 2 weeks, and they had greater numbers and more extensive rostro-caudal distribution of Fos neurons than the PX group. One week after PX injury, Fos-IR neurons were found in regions with strong Dyn-IR central fibers. Co-expression of Dyn and Fos was found in some unusually large neurons of the ipsilateral rostral lateral solitary nucleus, trigeminal tract, and dorsal nucleus caudalis. Immunocytochemistry for the p75 low affinity neurotrophin receptor (p75NTR) or for calcitonin gene-related peptide (CGRP) showed no consistent change in trigeminal central endings in any Fos-reactive brainstem areas, despite the extensive structural and cytochemical reorganization of the peripheral endings of the dental neurons. The Fos responses of central neurons to tooth injury have some unusual temporal and spatial patterns in adult rats compared to other trigeminal injury models.

Response properties of neurons in the caudate-putamen and globus pallidus to noxious and non-noxious thermal stimulation in anesthetized rats.

To investigate the possible mechanisms by which neurons in the caudate-putamen (CPu) and globus pallidus (GP) participate in pain and nociception, the present study characterized the response properties of CPu and GP neurons to non-noxious and noxious thermal stimuli in anesthetized rats. Nociceptive CPu and GP neurons were capable of encoding noxious thermal stimuli and 79% of these thermally responsive neurons also responded to noxious mechanical stimuli. Thermally responsive neurons were activated during the phasic rise and fall of the thermal shift in addition to the plateau temperature. The ability of CPu and GP neurons to encode noxious thermal stimulation intensity and respond during the dynamic phase of the stimulus suggests that these neurons may contribute to the behavioral response to minimize bodily harm.

Nerve growth factor depletion by autoimmunization produces thermal hypoalgesia in adult rats.

Nerve growth factor (NGF) plays a role in mechanisms of inflammation and hyperalgesia in adult animals. We sought to determine if NGF depletion produced by autoimmunization of adult rats altered their thermal sensitivity to an acute noxious thermal stimulus. Anti-NGF IgG was not detected in the cerebrospinal fluid of any tested samples. Only those rats with the highest anti-NGF serum titers showed significant (P < 0.05) thermal hypoalgesia measured using the hot plate test (52 degrees C): the mean (+/-S.D.) hind paw lick latency of rats in the high anti-NGF titer group was 18.0 +/- 4.6 s compared to means of 10.8 +/- 4.3 s, 9.2 +/- 2.6 s and 10.1 +/- 3.0 s in the medium, low and control groups, respectively. Thus, NGF depletion by autoimmunization is a useful model for investigating the role of NGF in behavioral responses of adult rats to noxious stimuli, providing high titers of antibody are present.

Behavioral outcome of posterior parietal cortex injury in the monkey.

Recent studies from our laboratory have characterized the response properties of trigeminal nociceptive neurons located in the posterior parietal cortex of awake monkeys, particularly in the rostral portion of the inferior parietal lobule and parietal operculum within the lateral sulcus. The stimulus intensity-response functions of some nociceptive neurons were significantly correlated to the stimulus intensity-escape frequency functions. The present study provides evidence that trauma to the posterior parietal cortex alters pain sensibility to the contralateral face. Although thermal pain tolerance was dramatically altered, the discriminative aspect of thermosensitivity may have remained intact. Our results complement the recent findings of clinical studies concerned with pain and damage to the posterior parietal cortex and of experimental studies concerned with painful stimulation and changes in regional cerebral blood flow. The role of the posterior parietal cortex in nociception and pain is discussed in relation to the first somatosensory area and to unilateral spatial neglect (inattention).

Axonal transport of fluorescent carbocyanine dyes allows mapping of peripheral nerve territories in gingiva.

Sensory innervation of gingival tissue can cause neurogenic inflammation that depends on the extent of the branching area of the peripheral nerve fibers. We designed the present study to determine whether single trigeminal axons branch to both the buccal and palatal gingiva of maxillary molars of adult rats. Accumulation via retrograde transport of DiI (red) or DiA (green) fluorescent carbocyanine dyes in neurons of trigeminal ganglia was evaluated 7 days after applying one dye to the buccal sulcus and the other to the palatal sulcus. Both dyes were absorbed through the junctional epithelium, and the two sites each labeled similar numbers and sizes of neurons in the lateral zone of the maxillary division (44% from buccal and 46% from palatal gingiva). Double-labeled neurons had the same size (32.5 +/- 6.70 microns, mean circumference +/- S.D.) and location as single-labeled neurons, and they were 9% of the total. This study shows that exogenous dyes can diffuse into mucosa and thereby allow in vivo mapping of sensory nerve branching patterns to several intact tissues per animal. We found that 9% of the labeled cells extended to both the buccal and palatal gingiva. Thus, inflammation that spreads from one gingival region to the other could have a neurogenic mechanism involving trigeminal sensory neurons that extend their peripheral branches to innervate both buccal and palatal gingiva of adult rat molars.

Multisensory convergence and integration in the neostriatum and globus pallidus of the rat.

The extracellular response properties of neurons in the caudate-putamen (CPu), globus pallidus (GP) and lateral amygdaloid nucleus (La) evoked by auditory and somatosensory stimuli were investigated. A total of 61 neurons in these areas responded either singly to somatosensory stimulation (unisensory), or to both somatosensory and auditory stimulation (multisensory). Higher rates of somatosensory stimulation reduced the response magnitude of CPu neurons more than that of GP neurons. In multisensory neurons, combined somatosensory and auditory stimulation compared to unisensory stimulation resulted in three characteristic response patterns: enhancement, depression or interaction. Temporal misalignment of the peak frequency latencies evoked by auditory and somatosensory stimulation altered the response magnitude in the majority of neurons. The response properties and anatomical connectivity of CPu and GP neurons suggest that the observed multisensory integrative effects may be used to facilitate motor responses to low intensity stimuli.

Somatosensory, multisensory, and task-related neurons in cortical area 7b (PF) of unanesthetized monkeys.

1. The goal of this study was to quantitatively characterize the response properties of somatosensory and multisensory neurons in cortical area 7b (or PF) of monkeys that were behaviorally trained to perform an appetitive tolerance-escape task. Particular emphasis was given to characterizing nociceptive thermal responses and correlating such responses to thermal pain tolerance as measured by escape frequency. 2. A total of 244 neurons that responded to somatosensory stimulation alone or to both somatosensory and visual stimulation (multisensory) were isolated and studied in the trigeminal region of cortical area 7b. Thirty neurons responded only to visual stimulation. Thermoreceptive neurons formed approximately 13% (31 of 244) of the neurons that had somatosensory response properties. Thermal nociceptive neurons made up approximately 9% (21 of 244) of the neurons that had somatosensory response properties or approximately 68% (21 of 31) of the neurons that had thermoreceptive response properties. Thermal nociceptive neurons responded either exclusively to noxious thermal stimuli (high-threshold thermoreceptive, HTT) or differentially to nonnoxious and noxious thermal stimuli (wide-range thermoreceptive, WRT). Multimodal HTT neurons had nonnociceptive (low-threshold mechanoreceptive, LTM) and/or nociceptive (nociceptive-specific, wide-dynamic-range) mechanical receptive fields, whereas multimodal WRT neurons had only nonnociceptive (LTM) mechanical receptive fields. Thermal nonnociceptive neurons (low-threshold thermoreceptive, LTT) made up approximately 3% (8 of 244) of the neurons that had somatosensory properties or approximately 26% (8 of 31) of the neurons that were thermoreceptive. The background discharge of two thermoreceptive neurons (6%, 2 of 31) was inhibited by innocuous thermal stimulation. 3. Thermal nociceptive neurons (HTT and WRT) were functionally differentiated by statistical analyses into subpopulations that did encode (HTT-EN, WRT-EN) and did not encode (HTT-NE, WRT-NE) the magnitude of noxious thermal stimulus intensities. The mean slopes and median regression coefficients for the stimulus-response (S-R) functions of HTT-EN and WRT-EN neurons, respectively, were significantly greater than those for the S-R functions of HTT-NE and WRT-NE neurons. In contrast to HTT-NE and WRT-NE neurons, HTT-EN and WRT-EN neurons reliably encoded the magnitude of noxious thermal intensity by grading their mean discharge frequency. 4. The S-R functions of HTT-EN and WRT-EN neurons, unlike those of HTT-NE and WRT-NE neurons, closely approximated stimulus intensity-escape frequency functions.(ABSTRACT TRUNCATED AT 400 WORDS)

Uptake of exogenous fluorescent Di-I by intact junctional epithelium of adult rats allows retrograde labeling of trigeminal sensory neurons.

Junctional epithelium (JE) is the special attachment tissue between gingiva and teeth, and it is well innervated by sensory nerve fibers. We have found that the fluorescent carbocyanine dye, Di-I, can penetrate quickly into intact JE and spread into connective tissue. Di-I containing neurons in trigeminal ganglion were found at 3-7 days and were mostly gone by 3 weeks. We conclude that substances such as Di-I can penetrate through permeable epithelia such as intact JE where they are picked up by sensory nerve fibers and carried to nerve cell bodies.

A simplified method for manufacturing glass-insulated metal microelectrodes.

A simplified method to manufacture durable, glass-insulated, tungsten microelectrodes with sufficient control of the final electrode impedance is described. This method requires only two instruments, an electrolytic etcher for wires and pipette puller, for manufacturing these electrodes. The manufacture of these electrodes involves 3 steps: (1) etching tungsten wire to sharpen the tip, (2) insulating the electrode by pulling a glass pipette over the sharpened tungsten wire and (3) assessing and adjusting the tip exposure and impedance of the electrode to meet recording requirements. Control over the electrode impedance is easily accomplished by varying the distance between the uppermost portion of the heating coil and the sharpened wire tip before a glass pipette is pulled over the wire tip. This distance determines the area of tip exposure and also the location where the glass insulation ends and the exposed electrode tip begins. A performance test of these electrodes in a chronically prepared monkey showed that they were strong enough to repeatedly penetrate thickened dura mater without significant changes in impedance and to isolate cortical neuronal activity after these multiple penetrations. Furthermore, the strength of these microelectrodes eliminated the need to remove reactive granular tissue from the dura overlying the recording site.

Nociceptive responses in the neostriatum and globus pallidus of the anesthetized rat.

1. Extracellular recordings were made from neurons in the neostriatum (caudate nucleus-putamen, CPu) and globus pallidus (GP) of anesthetized rats. Few cells (3%) were classified as low-threshold-mechanoreceptive (LTM) neurons. The majority (97%) of somatosensory CPu and GP neurons responded differentially or exclusively to noxious mechanical stimulation of the skin. Nociceptive neurons were classified into the following three groups on the basis of their response properties to noxious mechanical stimulation: wide-dynamic-range (WDR) neurons (21%); nociceptive-specific (NS) neurons (67%); and inhibited (INH) neurons (13%). 2. No differences in the response properties or in the proportions of WDR, NS, and INH neurons were found in the CPu compared with the GP. Nociceptive neurons were located most often along the CPu-GP border. Additionally, neurons of similar functional classification were often clustered within 200-400 microns of each other along a single microelectrode track. 3. The receptive fields of nociceptive CPu and GP neurons were often large and bilateral; some receptive fields encompassed the entire body. The trigeminal region, especially the perioral area, was included in the receptive fields of nociceptive neurons more often (62 of 63 cells) than any other part of the body. However, no preference for any particular division of the trigeminal nerve was observed in the receptive fields. Some neurons had receptive fields that were discontinuous. 4. Noxious pinching of the skin significantly increased the spontaneous neuronal discharge of WDR and NS neurons by an average of 482 and 221%, respectively. There were no significant differences between the discharge adaptation rates of WDR and NS neurons. Afterdischarge activity was observed in some WDR and NS neurons. INH neurons decreased their resting activity levels by an average of 43% after a noxious pinch. 5. The von Frey stimulus threshold of WDR neurons (11.0 g/mm2) was significantly lower than that of NS neurons (33.6 g/mm2) and INH neurons (32.6 g/mm2). Mean stimulus thresholds of WDR, NS, and INH neurons determined by using calibrated forceps were 1.6, 4.8, and 2.2 g/mm2, respectively. 6. Individual stimulus-response functions of nociceptive neurons were best fit by a negatively accelerating (logarithmic) curves. However, WDR neurons had significantly steeper slopes than NS neurons. 7. The results demonstrate that a large proportion of somatosensory neurons within the neostriatum and globus pallidus (especially along the CPu-GP border) receive nociceptive information. These data are discussed in relation to several putative afferent nociceptive pathways projecting to the CPu and GP.(ABSTRACT TRUNCATED AT 400 WORDS)

Static and dynamic responses of periodontal ligament mechanoreceptors and intradental mechanoreceptors.

1. The response properties of 39 periodontal ligament mechanoreceptors (PDLMs) and 12 intradental mechanoreceptors (IMs) related to the intact mandibular canine tooth were isolated by extracellular recording methods from the ipsilateral trigeminal semilunar ganglion. 2. The stimulus threshold and response magnitude of individual PDLMs depended on the direction of steady force applied to the intact canine tooth. Canine PDLMs as a population, however, did not have a preferred stimulus direction. IMs were activated only by a rapid mechanical transient applied to the intact tooth in any direction. The stimulus threshold and response magnitude of each IM were approximately equipotent in all stimulus directions. 3. Application of quantifiable ramp-and-hold stimulation showed that PDLMs can encode the intensity of steady forces as well as the rate of force ramps. Increasing the ramp rates decreased the total ramp discharge but increased the peak discharge frequency. IMs encoded only the rate of force ramps that were applied by percussion. Higher ramp rates increased both the total discharges and peak discharge frequency of IMs. 4. The dynamic response properties of PDLMs and IMs were clearly differentiated by sinusoidal vibratory stimulation. The maximum frequencies for entrainment of IM discharge at the stimulus cycle length (251 +/- 103 Hz, mean +/- SD) and at any periodicity including multiples of the stimulus cycle length (295 +/- 100 Hz) were significantly higher than the maximum frequencies for PDLM discharge entrainment at the stimulus cycle length (103 +/- 53 Hz) and at any periodicity (133 +/- 62 Hz). 5. The functional similarities of PDLMs and IMs, respectively, to slowly adapting type II mechanoreceptors and Pacinian corpuscle receptors in the skin are discussed. Our present findings, which complement earlier anatomic and behavioral evidence, strongly suggest that IMs subserve nonnociceptive and nonpain functions. Both PDLMs and IMs may provide a continuum of dynamic afferent inputs necessary for tactile sensibility of teeth.

Topography of C1 nerve- and trigeminal-evoked potentials in the ventrobasal complex of the cat thalamus.

In order to provide information pertaining to the C1 nerve representation in the thalamus, C1 nerve- and trigeminal-evoked potentials were recorded throughout the ventrobasal complex of the cat thalamus. Contralateral electrical stimulation of the C1 nerve and maxillary division of the trigeminal nerve elicited multiphasic positive-to-negative responses with mean maximum positive peak latencies of 2.2 ms and 2.7 ms, respectively. Ipsilateral stimulation failed to elicit a thalamic response. Construction of isopotential contour maps revealed that the foci of activity elicited by contralateral C1 nerve and trigeminal stimulation were located in the dorsolateral and ventromedial sections of ventroposterior medial nucleus (VPM), respectively.

Responses of cat C1 spinal cord dorsal and ventral horn neurons to noxious and non-noxious stimulation of the head and face.

Previous anatomical studies have shown that trigeminal and cervical afferent nerve fibers project to the upper cervical segments of the spinal cord. To determine the response properties of neurons in the upper cervical spinal cord, we studied the response of C1 dorsal and ventral horn cells to electrical and graded mechanical stimulation of the face, head and neck in anesthetized cats. Neurons were classified as low-threshold-mechanoreceptive (LTM), wide-dynamic-range (WDR), nociceptive-specific (NS) or unresponsive, based on their responsiveness to graded mechanical stimulation. Extracellular single unit recordings were obtained from 118 neurons excited by cervical (24), trigeminal (39) or both cervical and trigeminal (55) stimulation and from 24 neurons unresponsive to peripheral stimulation. Based on neuronal mechanical response properties, 52.2% of the responsive neurons were classified as LTM, 35.9% as WDR and 11.9% as NS. WDR neurons exhibited more convergence and had larger receptive fields than either NS or LTM neurons. WDR and NS neurons had longer first spike latencies than LTM neurons at all tested sites. Only WDR neurons were found to project to the contralateral caudal thalamus. Within C1, LTM neurons were located primarily in laminae III and IV, WDR neurons in lamina V and NS neurons in laminae VII and VIII. These data suggest that some neurons in the first cervical segment of the spinal cord receive convergent input from trigeminal and cervical pathways and may be involved in mediating orofacial and cranial pain.

Preproenkephalin upregulation in nucleus caudalis: high and low intensity afferent stimulation differentially modulate early and late responses.

Nucleus caudalis expression of preproenkephalin mRNA changes following lesions depleting small-caliber primary afferent fibers and after stimulation of trigeminal afferents at different intensities. Animals treated neonatally with capsaicin display reduced preproenkephalin gene expression in nucleus caudalis neurons. Stimulation of normal animals at low intensities enhances preproenkephalin expression in a bimodal temporal pattern. High intensity stimulation is effective only at later time points in normal animals, but it causes both early and late effects on preproenkephalin expression when applied to animals neonatally lesioned with capsaicin. Transsynaptic regulation of preproenkephalin expression in pain-modulating areas of the nucleus caudalis of the trigeminal nerve thus depends on the specific type of primary afferent input. The rapid responses noted after selective large fiber stimulation appear to be suppressed by coactivation of small caliber fibers. Later responses appear less influenced by the quality of the eliciting afferent stimulus.

Tooth pulp-evoked potentials in the trigeminal brainstem nuclear complex.

The surface and depth distributions of mandibular canine, tooth pulp-evoked potentials (TPEPs) in the trigeminal brainstem nuclear complex were studied in anesthetized cats. Three pairs of positive-negative waves or components were elicited from each trigeminal brainstem nucleus (main sensory, MSN; oralis, NO; interpolaris, NI; caudalis or medullary dorsal horn, NC). The location and dipole orientation of the current generator source for each pair of components in each nucleus were determined by using the topographic amplitude distribution of TPEPs in both their normal-reference and inverted polarities and the isoelectric contour line. The current sources for all components were the following: MSN--dorsomedial subnucleus; NO--dorsolateral portion; NI--dorsomedial portion; NC--medial part of superficial and intermediate laminae. These loci are consistent with the central terminal zones of mandibular tooth pulp afferents reported in previous neuroanatomical studies. Measurements of mean peak latencies suggest that tooth pulp A beta afferents contribute to the putatively presynaptic (P1-N1) and monosynaptic (P2-N2) components found in all trigeminal brainstem nuclei and that A delta afferents contribute to the later and possibly polysynaptic components (P3-N3) in the same nuclei. The pertinence of these findings to the theory that both non-nociceptive and nociceptive intradental inputs project to rostral and caudal nuclei are discussed.

Responses of nociceptive SI neurons in monkeys and pain sensation in humans elicited by noxious thermal stimulation: effect of interstimulus interval.

1. Twenty-six nociceptive neurons in the primary somatosensory cortex (SI) of anesthetized monkeys were responsive to noxious thermal stimulation applied to the face. Thermode temperature increased from a base line of 38 degrees C to temperatures ranging from 44 to 49 degrees C (T1). After a period of 5 s, the temperature increased an additional 1 degree C (T2). The neuronal responses to noxious thermal stimuli were compared when the interstimulus interval (ISI) was 30 or 180 s. 2. A linear regression analysis was applied to the stimulus-response functions of neuronal responses to T1 stimuli obtained at ISIs of 180 s. Based on the slopes and linear regression coefficients of these stimulus-response functions, two populations of nociceptive neurons were identified. The neuronal responses of one population of nociceptive SI neurons (WDR1) to T1 stimuli were characterized by steep slopes and high regression coefficients, whereas the other population (WDR2) had flatter slopes and lower regression coefficients. WDR1 neurons responded with monotonic increases in neuronal activity as the stimulus intensity increased. However, the peak frequency of WDR2 neurons often reached a plateau below 47 degrees C. Both WDR1 and WDR2 neurons had receptive fields that encompassed one or two divisions of the trigeminal nerve. 3. The T1 neuronal responses of WDR1 neurons were significantly suppressed when thermal stimuli were delivered with ISIs of 30 s. The T1 neuronal responses of WDR2 and the T2 responses of both WDR1 and WDR2 neurons were not significantly different when ISIs of 30 and 180 s were used. The T1 thresholds of WDR1 and WDR2 neurons were significantly higher when stimuli were delivered with ISIs of 30 s compared with ISIs of 180 s. 4. Most nociceptive SI neurons were located in layers III and IV of area 1-2. In a number of instances, multiple nociceptive neurons were found in the same microelectrode penetration. 5. The humans' intensity of pain sensation paralleled the neuronal responses of nociceptive SI neurons. With the use of a similar paradigm as in the monkey experiments, increases in T1 and T2 temperatures resulted in monotonic increases in pain ratings and change in pain sensation, respectively. However, the intensity of pain sensation to T1 temperatures was suppressed by ISIs of 30 s. Neither ISI produced statistically significant changes in the intensity of pain sensation to T2 stimuli. 6. These data demonstrate that manipulations that alter the intensity of pain sensation also produce concomitant changes in the responsiveness of nociceptive SI neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Distribution and size of GABAergic neurons in area 7b and the retroinsular cortex of the monkey.

The distribution of gamma-aminobutyric acid (GABA) neurons was examined in the retroinsular cortex (Ri) and area 7b of the monkey. GABA-immunoreactive somata and puncta were observed in all layers of Ri and area 7b. The densest concentration of these neurons was located in layers I and II. The vast majority (98.9%) of GABA-immunoreactive somata were less than 15 microns in major diameter. These data demonstrate that high concentrations of GABAergic neurons are located in those cortical layers that have been shown to receive afferent projections from corticocortical fibers.

Distribution of GAD-immunoreactive neurons in the first (SI) and second (SII) somatosensory cortex of the monkey.

The distribution of neurons immunoreactive for glutamic acid decarboxylase (GAD), the synthesizing enzyme of gamma-aminobutyric acid (GABA), was examined in the first (SI) and second (SII) somatosensory cortex of monkeys. GAD-like immunoreactive (GAD-LI) somata and puncta were present in all layers of SI and SII. All GAD-LI somata were identified as non-pyramidal neurons and were most numerous in layer IV of SI and in layer III of SII. Layer IV of SI also contained the highest density of GAD-LI puncta. In SII, GAD-LI puncta were distributed more homogeneously and did not show a dense band of labelled puncta in layer IV. The major and minor diameters of GAD-LI somata in SII ranged from 6.9 to 26.2 micron and from 6.2 to 19.0 micron, respectively. The major diameters of GAD-LI somata in SII were significantly smaller than those in SI in layers I, III and IV. Differences between the distributions of GAD-LI puncta and somata in SI and SII may be accounted for by differences in the number and/or distribution of different types of GABAergic neurons. Functional differences of neurons in SI and SII may be related to the differences in GABAergic inhibitory mechanisms and reflected in the distribution of GABAergic neurons.

SI nociceptive neurons participate in the encoding process by which monkeys perceive the intensity of noxious thermal stimulation.

The activity of primary somatosensory (SI) cortical nociceptive neurons was recorded while the monkeys performed a psychophysical task in which they detected small increases in skin temperature superimposed on noxious levels of thermal stimulation. The detection latency to these stimuli, expressed as detection speed, was used as a measure of the perceived intensity of sensation. Two-thirds of the neurons that responded to noxious thermal stimulation increased their discharge in response to graded increases in stimulus intensity. The remaining neurons responded to noxious thermal stimulation, but did not grade their response with the intensity of the stimulus. The response of SI nociceptive neurons that encode the intensity of noxious thermal stimulation was significantly correlated with the monkey's detection speed. We conclude that SI nociceptive neurons are involved in the encoding process by which monkeys perceive the intensity of noxious thermal stimulation.

Cortical nociceptive responses and behavioral correlates in the monkey.

Experiments were performed to characterize cerebral cortical activity and pain behavior elicited by electrical stimulation of the tooth pulp in unanesthetized monkeys. Four monkeys were trained on two different operant paradigms: two on a simple escape task and two on an appetitive tolerance-escape task. All monkeys were implanted with bipolar stimulating electrodes in the right maxillary canine tooth and subdural recording electrodes over the left primary (SI) and/or secondary (SII) somatosensory cortices. Subdural tooth pulp-evoked potentials (TPEPs) recorded over the SII consisted of components P1 (27.5 ms), N1 (40.3 ms), P2 (84.0 ms), N2 (163.5 ms), P3 (295.3 ms), and N3 (468.0 ms). The long latency component (P3-N3) was found exclusively over the SII and was elicited by high intensity stimulation. The appearance of component P3-N3 required the recruitment of A delta nerve fibers into the maxillary nerve compound action potential and was correlated with high frequencies of escape. Administration of morphine sulfate (4 mg/kg, i.m.) caused a contemporaneous reduction in escape frequency and in the amplitude of P3-N3 recorded over the SII. The relationships between TPEP amplitude, escape behavior and A delta nerve fiber activity strongly suggest that the SII is involved with nociception and pain behavior.