High-threshold Cells Research Articles

Cellular mechanisms for response heterogeneity among L2/3 pyramidal cells in whisker somatosensory cortex.

Whisker deflection evokes sparse, low-probability spiking among L2/3 pyramidal cells in rodent somatosensory cortex (S1), with spiking distributed nonuniformly between more and less responsive cells. The cellular and local circuit factors that determine whisker responsiveness across neurons are unclear. To identify these factors, we used two-photon calcium imaging and loose-seal recording to identify more and less responsive L2/3 neurons in S1 slices in vitro, during feedforward recruitment of the L2/3 network by L4 stimulation. We observed a broad gradient of spike recruitment thresholds within local L2/3 populations, with low- and high-threshold cells intermixed. This recruitment gradient was significantly correlated across different L4 stimulation sites, and between L4-evoked and whisker-evoked responses in vivo, indicating that a substantial component of responsiveness is independent of tuning to specific feedforward inputs. Low- and high-threshold L2/3 pyramidal cells differed in L4-evoked excitatory synaptic conductance and intrinsic excitability, including spike threshold and the likelihood of doublet spike bursts. A gradient of intrinsic excitability was observed across neurons. Cells that spiked most readily to L4 stimulation received the most synaptic excitation but had the lowest intrinsic excitability. Low- and high-threshold cells did not differ in dendritic morphology, passive membrane properties, or L4-evoked inhibitory conductance. Thus multiple gradients of physiological properties exist across L2/3 pyramidal cells, with excitatory synaptic input strength best predicting overall spiking responsiveness during network recruitment.

Reduction in inflammation-induced sensitization of dorsal horn neurons by transcutaneous electrical nerve stimulation in anesthetized rats.

Transcutaneous electrical nerve stimulation (TENS) is utilized to treat a variety of painful conditions. Inflamed animals present with an increased response to noxious stimuli, i.e., hyperalgesia, at the site of injury (primary hyperalgesia) and outside the site of injury (secondary hyperalgesia). Further, following acute inflammation, dorsal horn neurons show an increased responsiveness to peripherally applied stimuli, which has been termed sensitization. Previous studies demonstrate a reduction in dorsal horn neuron activity following TENS treatment in normal animals and a reduction in primary and secondary hyperalgesia in acutely inflamed animals. The purpose of this study was to examine the effects of TENS on dorsal horn neurons sensitized by acute inflammation. Extracellular recordings from wide dynamic range (WDR), high threshold (HT) and low threshold (LT) dorsal horn neurons in anesthetized rats were assessed for spontaneous activity, responses to innocuous and noxious mechanical stimulation and receptive field size. Responses were measured before and 3 h after induction of inflammation, and immediately and 1 h after application of either high (100 Hz) or low (4 Hz) frequency TENS (motor intensity, pulse duration = 100 microseconds). TENS was applied to the inflamed paw to encompass the receptive field of the neuron for 20 min. WDR and HT dorsal horn neurons sensitized to mechanical stimulation after induction of inflammation. Application of either high or low frequency TENS to the inflamed paw reduced both innocuous and noxious evoked responses of WDR and HT dorsal horn neurons immediately and 1 h after treatment with TENS. Comparison of responses after TENS with baseline responses showed that the evoked responses in the majority of WDR and HT cells returned to or fell below baseline responses. TENS had no effect on responses of LT neurons. In summary, central neuron sensitization is reduced by TENS and may underlie the reduction in hyperalgesia observed after treatment with TENS.

Alterations in ascending dorsal horn neurons by a surgical incision in the rat foot.

Little is known about the mechanisms of pain caused by a surgical incision. The authors have developed a rat model of postoperative pain characterized by decreased withdrawal thresholds to punctate mechanical stimuli after plantar incision. The present studies examined the response characteristics of dorsal horn neurons receiving input from the plantar aspect of the foot before and after a plantar incision placed adjacent to the low threshold area of the receptive field (RF). Individual dorsal horn neurons from the lumbar enlargement were antidromically identified and characterized as low threshold, wide dynamic range (WDR), and high threshold (HT) based on their responses to brush and pinch. Thresholds (in millinewtons), the pinch RF, and stimulus-response functions (SRFs) to von Frey filaments characterized the neurons. SRFs were analyzed using area under the curve. Changes in background activity, punctate mechanical thresholds, SRFs, and RF were recorded after an incision was made adjacent to the most sensitive area of the RF. In all cells, an incision increased background activity; this remained elevated in 3 of 9 HT and 16 of 28 WDR neurons 1 h later. The SRFs were enhanced in 10 of 27 WDR neurons and in 2 of 8 HT cells after incision. Only the WDR neurons were responsive to filaments that produced withdrawal responses after incision in behavioral experiments. Increases in the RFs outside of the injured area occurred after incision in 15 of 29 WDR and 2 of 9 HT cells. A plantar incision caused dorsal horn cell activation and central sensitization. Because the threshold of HT neurons did not decrease to the range of the withdrawal responses in behavioral experiments, particular WDR dorsal horn neurons likely contribute to the reduced withdrawal threshold observed in behavioral experiments. Both WDR and HT neurons are capable of transmitting enhanced responses to strong punctate mechanical stimuli after incision.

Mechanisms of Pain Caused by Surgical Incision Investigated in a Rat Model.

Mechanisms of Pain Caused by Surgical Incision Investigated in a Rat Model. Vandermeulen et al.(page 1294)Sensitization of the dorsal horn of the spinal cord via surgery (termed central sensitization) is not well-defined. Hypothesizing that a surgical incision would produce activation and enhanced responsiveness of single dorsal horn neurons, Vandermeulen et al. used a previously developed rat incisional pain model to study spontaneous and evoked activity from individual dorsal horn neurons in the lumbar spinal cord directly. After performing laminectomy in halothane-anesthetized rats, dorsal horn neurons from the lumbar enlargement were identified antidromically and characterized as low threshold, wide dynamic range, or high threshold based on their responses to brush and pinch of the animals’ paws. The receptive field for each neuron also was mapped. Then, an incision was made within the receptive field. Changes in background activity, punctate mechanical thresholds, receptive field size, and stimulus–response functions were recorded for up to 1 h after incision.In all cells, incisions produced a strong response and an increase in background activity, which remained increased in 3 of 9 high-threshold neurons and 16 of 28 wide-dynamic-range neurons 1 h later. The mechanical responsiveness was enhanced in 10 of 27 wide-dynamic-range neurons and in 2 of 8 high-threshold cells after incision. Wide-dynamic-range neurons may be the most important for pain signaling, and the increased background activity in these dorsal horn neurons may signal pain at rest after surgery. The receptive field size also expanded beyond the initial area around the incision, indicating a mechanism for amplification of dorsal horn response via surgery.

Position of spinothalamic tract axons in upper cervical spinal cord of monkeys.

Percutaneous upper cervical cordotomy continues to be performed on patients suffering from several types of severe chronic pain. It is believed that the operation is effective because it cuts the spinothalamic tract (STT), a primary pathway carrying nociceptive information from the spinal cord to the brain in humans. In recent years, there has been controversy regarding the location of STT axons within the spinal cord. The aim of this study was to determine the locations of STT axons within the spinal cord white matter of C2 segment in monkeys using methods of antidromic activation. Twenty lumbar STT cells were isolated. Eleven were classified as wide dynamic range neurons, six as high-threshold cells, and three as low-threshold cells. Eleven STT neurons were recorded in the deep dorsal horn and nine in superficial dorsal horn. The axons of the examined neurons were located at antidromic low-threshold points (<30 microA) within the contralateral lateral funiculus of C2. All low-threshold points were located ventral to the denticulate ligament, within the lateral half of the ventral lateral funiculus (VLF). None were found in the dorsal half of the lateral funiculus. The present findings support our previous suggestion that STT axons migrate ventrally as they ascend the length of the spinal cord. Also, the present findings indicate that surgical cordotomies that interrupt the VLF in C2 likely disrupt the entire lumbar STT.

Locations of spinothalamic tract axons in cervical and thoracic spinal cord white matter in monkeys.

The spinothalamic tract (STT) is the primary pathway carrying nociceptive information from the spinal cord to the brain in humans. The aim of this study was to understand better the organization of STT axons within the spinal cord white matter of monkeys. The location of STT axons was determined using method of antidromic activation. Twenty-six lumbar STT cells were isolated. Nineteen were classified as wide dynamic range neurons and seven as high-threshold cells. Fifteen STT neurons were recorded in the deep dorsal horn (DDH) and 11 in superficial dorsal horn (SDH). The axons of 26 STT neurons were located at 73 low-threshold points (<30 microA) within the lateral funiculus from T(9) to C(6). STT neurons in the SDH were activated from 33 low-threshold points, neurons in the DDH from 40 low-threshold points. In lower thoracic segments, SDH neurons were antidromically activated from low-threshold points at the dorsal-ventral level of the denticulate ligament. Neurons in the DDH were activated from points located slightly ventral, within the ventral lateral funiculus. At higher segmental levels, axons from SDH neurons continued in a position dorsal to those of neurons in the DDH. However, axons from neurons in both areas of the gray matter were activated from points located in more ventral positions within the lateral funiculus. Unlike the suggestions in several previous reports, the present findings indicate that STT axons originating in the lumbar cord shift into increasingly ventral positions as they ascend the length of the spinal cord.

Responses of Wide Dynamic Range and High Threshold Dorsal Horn Neurons Studied. Zahn et al. (page 772)

Using their rat model, Zahn et al. designed a set of experiments for human postoperative pain to determine whether mechanically insensitive areas of the receptive field of the dorsal horn neuron could be converted to areas responsive to weak mechanical stimuli. The researchers induced anesthesia with 4% halothane in 59 adult male Sprague-Dawley rats, prepared for intravenous administration of fluids and drugs, and then performed limited laminectomies at the cervical and thoracolumbar level. Electrodes were inserted into the C1 segment for antidromic stimulation, and action potentials of the dorsal horn neurons were recorded. Cells were classified as wide dynamic range (WDR) or high threshold (HT) depending on responses to brushing or pinching of the rat's left foot. HT cells responded to pinch only, whereas WDR neurons responded to brushing with von Frey filaments and even more strongly to pinch stimuli.Of 50 neurons recorded (29 WDR and 21 HT cells), only 9 showed a sustained increase in background activity after incision. In 9 of 28 WDR neurons, there was a marked decrease in threshold to von Frey filaments applied adjacent to the wound. A blunt mechanical stimulus (a 5-mm plastic disk) applied directly on the incision activated 18 of 22 WDR neurons, but HT cells were not excited by this stimulus after incision. The expansion of pinch receptive fields outside the injury area was common and similar in both WDR and HT neurons. The data suggest that conversion of mechanically insensitive areas of WDR neurons to areas responsive to weak mechanical stimuli could contribute to pain behaviors caused by punctate and blunt mechanical stimuli, but do not explain secondary hyperalgesia, the reasons for which must be examined further.

Incision-induced Changes in Receptive Field Properties of Rat Dorsal Horn Neurons

To learn more about pain mechanisms produced by surgery, responses of wide dynamic range (WDR) and high threshold (HT) dorsal horn neurons were studied before and after an incision. For this study, an incision was made in a mechanically insensitive area of the receptive field (RF) of the dorsal horn neuron in the plantar aspect of the foot and changes in mechanical response properties were studied. Action potentials from single dorsal horn neurons were recorded in halothane anesthetized rats and these neurons were characterized as WDR or HT. Changes in background activity and responses to a variety of mechanical stimuli adjacent to the incision, distant to the injury, and in areas throughout the hindquarters were recorded. Fifty neurons were recorded (29 WDR, 21 HT cells); only nine of these had a sustained increase in background activity after incision. Marked decreases in threshold to von Frey filaments applied adjacent to the wound occurred in 9 of 28 WDR neurons but in none of 21 HT cells. Von Frey filament thresholds distant to the incision were largely not changed. A blunt mechanical stimulus activated 18 of 22 WDR neurons when applied directly on the incision. HT cells were largely not excited by this mechanical stimulus after incision. The RF to pinch was enlarged in 31 neurons to include areas outside the injury. Pinch RFs of both WDR and HT cells expanded. These results suggest that incisions in mechanically insensitive areas of the RF of dorsal horn neurons produced little change in background activity; expansion of pinch RFs outside the injury was common. Changing a mechanically insensitive area of the RF of WDR neurons to a mechanically sensitive area by an incision could contribute to pain behaviors that indicate primary mechanical hyperalgesia in behavioral studies.

Nitric oxide-mediated spinal disinhibition contributes to the sensitization of primate spinothalamic tract neurons.

This study concentrated on whether an increase in spinal nitric oxide (NO) diminishes inhibition of spinothalamic tract (STT) cells induced by activating the periaqueductal gray (PAG) or spinal glycinergic and GABAergic receptors, thus contributing to the sensitization of STT neurons. A reduction in inhibition of the responses to cutaneous mechanical stimuli induced by PAG stimulation was seen in wide dynamic range (WDR) STT cells located in the deep layers of the dorsal horn when these neurons were sensitized during administration of a NO donor, 3-morpholinosydnonimine (SIN-1), into the dorsal horn by microdialysis. In contrast, PAG-induced inhibition of the responses of high-threshold (HT) and superficial WDR STT cells was not significantly changed by spinal infusion of SIN-1. A reduction in PAG inhibition when STT cells were sensitized after intradermal injection of capsaicin could be nearly completely blocked by pretreatment of the dorsal horn with a NO synthase inhibitor, 7-nitroindazole. Moreover, spinal inhibition of nociceptive activity of deep WDR STT neurons elicited by iontophoretic release of glycine and GABA agonists was attenuated by administration of SIN-1. This change paralleled the change in PAG-induced inhibition. However, the inhibition of HT and superficial WDR cells induced by glycine and GABA release did not show a significant change when SIN-1 was administered spinally. Combined with our recent results, these data show that the effectiveness of spinal inhibition can be reduced by the NO/cGMP pathway. Thus disinhibition may constitute one mechanism underlying central sensitization.

Vagal, sympathetic and somatic sensory inputs to upper cervical (C1-C3) spinothalamic tract neurons in monkeys.

1. Myocardial ischemia activates vagal and sympathetic cardiac afferent fibers. The purpose of this study was to determine a neuro physiological basis for cardiac pain referred to C1-C3 somatic dermatomes. We hypothesized that afferent fibers traveling in vagal or sympathetic nerves transmit nociceptive information to C1-C3 spinothalamic tract (STT) neurons. 2. Electrical stimulation of the left stellate ganglion to excite cardiopulmonary sympathetic afferent fibers increased extracellular activity of 44 of 77 C1-C3 STT neurons examined in 33 anesthetized male monkeys (Macaca fascicularis); responses increased as stimulus strength increased. Additionally, this stimulus inhibited 5 cells, increased/decreased activity of 2 cells, and did not affect 26 cells. 3. Electrical stimulation of the left (ipsilateral) thoracic vagus nerve excited 41 of 78 C1-C3 STT neurons, inhibited 4 neurons, increased/decreased activity of 2 neurons, and did not affect 31 neurons. Responses increased with increasing stimulus strength Contralateral vagal stimulation excited 7 of 39 cells tested, inhibited 4 cells and did not affect 28 cells. 4. Effects of stimulating one or more vagal branches were examined on 22 C1-C3 STT neurons excited by input from left thoracic vagus nerve. Stimulation of the cardiac branch excited 11 of 16 cells tested; stimulation of the recurrent laryngeal nerve excited 11 of 18 cells; stimulation of vagal fibers just rostral to the diaphragm excited 8 of 19 cells. 5. Excitatory somatic receptive fields ranged from small ipsilateral fields to large, sometimes bilateral or noncontinuous fields. Many fields included the ipsilateral neck and/or inferior jaw. Thirty-nine of 74 neurons examined were wide dynamic range (WDR), 21 were high threshold (HT), 6 were low threshold (LT), and 8 did not respond to brushing or noxious pinching of somatic tissues. Most (38 of 39) WDR cells responded to stimulation of the stellate ganglion or vagal fibers, as did 18 of 21 HT cells, 3 of 6 LT cells, and 2 of 8 cells unresponsive to brush or pinch stimuli. 6. Results of this study supported the concept that vagal and/ or sympathetic afferent activation of C1-C3 STT neurons might provide a neural mechanism for referred pain that originates in the heart or other visceral organs but is perceived in the neck and jaw region. Additionally, C1-C3 STT neurons processed sensory information from widespread regions of the body.

Vagal afferent fibers excite upper cervical neurons and inhibit activity of lumbar spinal cord neurons in the rat

Effects of electrical stimulation of the cervical vagus nerve were determined in cervical or lumbar spinal neurons in 27 rats anesthetized with pentobarbital. Ipsilateral cervical vagus stimulation (ICVS) increased activity of 44 neurons in the C 1 segment. At the same stimulation parameters, contralateral cervical vagus stimulation (CCVS) either increased, decreased or did not affect activity of C 1 neurons that were excited by ICVS. For C 1 cells excited by both ICVS and CCVS, the mean latency for activation was significantly longer for CCVS than for ICVS, and ICVS produced a greater degree of excitation than CCVS. In segments C 2-C 6, 16 of 18 neurons were excited by ICVS and 2 were inhibited. However, CCVS did not excite the C 2-C 6 neurons but either inhibited or did not affect activity. In 6 cervical cells, a CCVS conditioning stimulus reduced the level of excitation by ICVS (test stimulus). Transection of the C 2 or C 3 dorsal roots did not significantly affect the excitatory vagal input to C 1 cells. Excitatory somatic receptive fields were classified for 60 cervical spinal cells that responded to vagal stimulation. Most (87%) cells were excited by noxious pinch; 29 were wide dynamic range (WDR) cells and 21 were high threshold cells. In contrast to upper cervical neurons, spinothalamic tract (STT) and spinal cells in lumbar segments were not excited by ICVS or CCVS at the stimulation parameters used in this study, but were primarily inhibited by vagal stimulation. Results of this study showed that a group of cells in upper cervical segments were excited by vagal afferents. This excitatory vagal input reaches the C 1 segment primarily via an ipsilateral, supraspinal route.

Anesthetic blockade of the dorsolateral funiculus enhances evoked activity of spinal cord dorsal horn neurons.

1. A previous study of cat lumbar dorsal horn neurons found reduced responsiveness to A-fiber stimulation 1.5-12 h after thoracic dorsolateral funiculus (DLF) lesions. The present study was undertaken to determine whether this was due to the loss of descending activity or to factors specifically associated with injury by examining the response properties of dorsal horn cells before and during lidocaine blockade of the ipsilateral DLF. Electric shocks applied to the dorsal columns were used to search for dorsal horn cells. Noxious and nonnoxious cutaneous mechanical stimuli and graded electrical stimuli applied to the tibial nerve were used to activate peripheral afferent fibers. Cells were classed as low threshold (LT), high threshold (HT), or multireceptive (MR), according to their responses to natural stimuli. Baseline data were collected from a total of 58 cells. Twelve of these were further studied after lidocaine injection of the DLF. All cells examined with lidocaine were in dorsal horn laminae III-V. 2. All cells responded to activation of tibial nerve A fibers. However, the median threshold for the HT and MR cells (200 microA) was significantly higher than that of the LT cells (75 microA). Some cells in each class were also activated by C fibers (10, 70, and 64% of the LT, HT, and MR cells, respectively). 3. For the cells that were further characterized by lidocaine blockade of the DLF, all LT cells (n = 3) responded only to A-fiber stimulation, and all HT (n = 3) and MR cells (n = 6) responded to both A- and C-fiber stimulation. 4. For LT cells, responses evoked by mechanical and electrical stimuli were unaltered by lidocaine blockade. 5. HT and MR cells showed enhanced responses to electrical stimulation of C fibers during DLF blockade. There was no consistent effect of the blockade on A-fiber-evoked responses. 6. Two of three HT and four of six MR cells studied with lidocaine had spontaneous activity, which exhibited a small but significant increase during DLF blockade. 7. Receptive fields for noxious stimulation expanded in two of six MR cells during DLF blockade. Two of three HT cells developed responses to tactile stimuli during the blockade. 8. In two additional cells (1 HT and 1 MR), spontaneous activity and responses to C-fiber input increased after the DLF was cut.(ABSTRACT TRUNCATED AT 400 WORDS)

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)

Synaptic effects on recruitment gain: a mechanism of importance for the input-output relations of motoneurone pools?

The present theoretical analysis concerns quantitative aspects of the gradation of motoneuronal recruitment. It is pointed out that variations in the relative distribution of synaptic input to low- and high-threshold cells will serve to alter ultimate magnitude of the threshold differences between them. These threshold differences determine the pool's ‘recruitment gain’, i.e. the ease with which a variation of excitatory drive to the pool may alter the number of active motoneurons. In this context, not only the command signal itself but also any steady synaptic ‘background’ activity is of importance, whereby the background effects on recruitment gain depend on the presence of differences in intra-pool distribution between these synapses and those of the command signal. Given the appropriate intra-pool distribution, even inhibitory background effects might serve to increase the recruitment gain. It is stressed that synaptic effects on recruitment gain should be taken into account when analyzing the input-output relations of motoneurone pools.

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.

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.

Response characteristics of neurons in the ventral posterior lateral nucleus of the monkey thalamus.

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

Structure-function relationships in rat medullary and cervical dorsal horns. II. Medullary dorsal horn cells.

In Nembutal-anesthetized rats, 31 physiologically identified medullary dorsal horn (MDH) cells were labeled with horseradish peroxidase (HRP). Ten responded only to deflection of one or more vibrissae. Six cells were activated by guard hair movement only, six by deflection of guard hairs or vibrissa(e), and seven by pinch of facial skin with serrated forceps. Different classes of low-threshold cells could not be distinguished on the basis of their somadendritic morphologies or laminar distribution. Neurons activated by multiple vibrissae were unique, however, in that one sent its axon into the medial lemniscus, and three projected into the trigeminal spinal tract. None of the guard hair-only or vibrissae-plus-guard hair neurons had such projections. Cells that responded best to noxious stimulation were located mainly in laminae I, II, and deep V, while neurons activated by vibrissa(e) and/or guard hair deflection were located in layers III, IV, and superficial V. Low-threshold neurons generally had fairly thick dendrites with few spines, whereas high-threshold cells tended to have thinner dendrites with numerous spines. Moreover, the dendritic arbors of low-threshold cells were, for the most part, denser than those of the noxious cells. Neurons with mandibular receptive fields were located in the dorsomedial portion of the MDH; cells with ophthalmic fields were found in the ventrolateral MDH, and maxillary cells were interposed. Cells sensitive to deflection of dorsal mystacial vibrissae and/or guard hairs were located ventral to those activated by more ventral hairs. Neurons with rostral receptive fields were found in the rostral MDH, while cells activated by hairs of the caudal mystacial pad, periauricular, and periorbital regions were located in the caudal MDH. Receptive-field types were encountered that have not been reported for trigeminal primary afferent neurons: multiple vibrissae; vibrissae plus guard hairs; and wide dynamic range. The latter two can be explained by the convergence of different primary afferent types onto individual neurons. Our failure to find a significant relationship between dendritic area (in the transverse plane) and the number of vibrissae suggests that primary afferent convergence may not be responsible for the synthesis of the multiple vibrissae receptive field. Excitatory connections between MDH neurons may, therefore, account for multiple vibrissae receptive fields in the MDH.

Response and receptive-field properties of spinomesencephalic tract cells in the cat.

Recordings were made from 90 identified spinomesencephalic tract (SMT) cells in the lumbosacral spinal cord of cats anesthetized with alpha-chloralose and pentobarbital sodium. Recording sites were located in laminae I-VIII. Antidromic stimulation sites were located in different regions of the rostral and caudal midbrain including the periaqueductal gray, midbrain reticular formation, and the deep layers of the superior colliculus. Twelve SMT cells were antidromically activated from more than one midbrain level or from sites in the medial thalamus. The mean conduction velocity for the population of cells sampled was 45.2 +/- 21.4 m/s. Cells were categorized based on their responses to graded intensities of mechanical stimuli and the location of excitatory and/or inhibitory receptive fields. Four major categories of cells were encountered: wide dynamic range (WDR); high threshold (HT); deep/tap; and nonresponsive. WDR and HT cells had excitatory and/or inhibitory receptive fields restricted to the ipsilateral hindlimb or extending to other parts of the body including the tail, forelimbs, and face. Some cells had long afterdischarges following noxious stimulation, whereas others had high rates of background activity that was depressed by nonnoxious and noxious stimuli. Deep/tap cells received convergent input from muscle, joint, or visceral primary afferent fibers. The placement of mechanical lesions at different rostrocaudal levels of the cervical spinal cord provided information related to the spinal trajectory of SMT axons. Six axons were located contralateral to the recording electrode in the ventrolateral/medial or lateral funiculi while two were located in the ventrolateral funiculus of the ipsilateral spinal cord. Stimulation at sites used to antidromically activate SMT cells resulted in the inhibition of background and evoked responses for 22 of 25 cells tested. Inhibitory effects were observed on responses evoked by low/high intensity cutaneous stimuli and by the activation of joint or muscle primary afferent fibers. Based on the response and receptive-field properties of SMT cells it is suggested that the SMT may have an important role in somatosensory mechanisms, particularly those related to nociception.

Activation of dorsal horn cells by ventral root stimulation in the cat.

Responses of dorsal horn cells to ventral root stimulation were determined for the L7 and S1 levels of the spinal cord of 14 anesthetized cats. Forty-six dorsal horn cells were found that were excited by stimulation of the distal stump of the cut ventral root. For maximum excitation it was necessary to use a train of stimuli. For the 34 dorsal horn cells whose peripheral receptive-field properties could be characterized, 14 were wide dynamic range cells and 19 were high-threshold cells. The other cell responded exclusively to stimulation of deep tissue. None of the cells responded exclusively to innocuous stimuli, and all responded more vigorously to noxious than to innocuous stimuli. Some cells also responded to noxious heat applied to the skin of the receptive field. Locations of 10 of the activated dorsal horn cells were identified. They were distributed throughout the dorsal horn, but most were found in laminae V and VI. In four animals, both the proximal and distal stumps of the cut S1 ventral root were stimulated while searching for dorsal horn cells. Ten dorsal horn cells were found that were excited by stimulation of the distal stump of the ventral root. No cells were found that responded to proximal stump stimulation. To prevent current spread by stimulation of the ventral root, an extra ground electrode was placed distal to the stimulating electrodes. When the ground electrode was removed, distinctive signs of current spread appeared in that a cord dorsum potential could be recorded and the dorsal horn neuronal responses changed. Dorsal horn neurons could also be excited by nonelectrical stimuli such as crushing the ventral root. If the ventral root was crushed distal to the stimulating electrodes, however, the initially excited cell could no longer be activated by ventral root stimulation. Activation of dorsal horn cells by stimulation of the distal stump of a cut ventral root was abolished when the dorsal root of the same segment was sectioned. Conduction velocities of the fibers in the ventral root that excited dorsal horn cells ranged between 0.25 and 1.78 m/s with a mean of 0.91 +/- 0.47 (SD) m/s. These results show that there are unmyelinated afferent fibers in the ventral root that enter the spinal cord through the dorsal root and excite dorsal horn cells.(ABSTRACT TRUNCATED AT 400 WORDS)