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Biomedical subjects

A V Apkarian

Publications and source records attributed to A V Apkarian.

At least 19 recordsLinked to original sources

Persistent pain inhibits contralateral somatosensory cortical activity in humans.

To assess cortical activity during pain perception, regional cerebral blood flow (rCBF) studies were done in humans using single photon emission computed tomography (SPECT) with the radiotracer Tc99m-HMPAO and magnetic resonance imaging localization. Normalized SPECT data were analyzed by region of interest and change distribution. Contralateral somatosensory rCBF was decreased when the digits of the hand were immersed in a hot water bath for 3 min which was rated as moderately painful (persistent pain). No decrease was observed when the hand was immersed in tepid water (control). In contrast, cortical rCBF was increased during vibratory and sensorimotor tasks, in the contralateral somatosensory and sensorimotor areas, respectively. These results indicate that pain perception in man is associated with somatosensory cortical inhibition.

Adult

Thalamically projecting cells of the lateral cervical nucleus in monkey.

The number, location, and morphology of thalamically projecting lateral cervical nucleus (LCN) cells were determined in monkey using retrograde transport of wheatgerm agglutinin-conjugated horseradish peroxidase. These data were compared to the total population of LCN neurons as determined by Nissl stain. In 4 Macaca fascicularis and one Saimiri sciureus the average size of the thalamic projection from LCN was found to be 506 +/- 94 cells contralateral to the injections. Thalamically projecting LCN neurons were located between the lower medulla and the third cervical segment; approximately 90% of these cells were in the first two cervical segments. Morphologic analysis of thalamically projecting LCN cells showed that they were smaller in size, and more oblong in shape in caudal regions of the nucleus. In 3 macaques, the average total number of LCN cells was determined to be 1617 +/- 908 on one side, in Nissl material. In these Nissl-stained preparations LCN neurons were found as far caudal as the fourth cervical segment; 68% were located in the first two cervical segments. Hence, thalamically projecting LCN neurons in the monkey are located in the rostral portion of the nucleus and comprise about one-third of the total population. Comparison of these data with reports in the literature imply that, unlike the cat, the major projection from LCN in monkeys is to the mesencephalon rather than to the thalamus.

Animals

Anatomic evidence of nociceptive inputs to primary somatosensory cortex: relationship between spinothalamic terminals and thalamocortical cells in squirrel monkeys.

This study examined anatomic pathways that are likely to transmit noxious and thermal cutaneous information to the primary somatosensory cortex. Anterograde and retrograde labeling techniques were combined to investigate the relationship between spinothalamic (STT) projections and thalamocortical neurons in the squirrel monkey (Saimiri sciureus). Large injections of diamidino yellow (DY) were placed in the physiologically defined hand region of primary somatosensory cortex (hSI), and wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected in the contralateral cervical enlargement (C5-T1). Both DY-labeled neuronal cell bodies and HRP-labeled STT terminal-like structures were visualized within single thalamic sections in each animal. Quantitative analysis of the positions and numbers of retrogradely labeled neurons and anterogradely labeled terminal fields reveal that: 1) ventral posterior lateral (VPL), ventral posterior inferior (VPI), and central lateral (CL), combined, receive 87% of spinothalamic inputs originating from the cervical enlargement; 2) these three nuclei contain over 91% of all thalamocortical neurons projecting to hSI that are likely to receive STT input; and 3) these putatively contacted neurons account for less than 24% of all thalamic projections to hSI. These results suggest that three distinct spinothalamocortical pathways are capable of relaying nociceptive information to the hand somatosensory cortex. Moreover, only a small portion of thalamocortical neurons are capable of relaying STT-derived nociceptive and thermal information to the primary somatosensory cortex.

Animals

Somatosensory response properties of contralaterally projecting spinothalamic and nonspinothalamic neurons in the second cervical segment of the cat.

1. The upper cervical spinal cord contains over one-third of the cells of the spinothalamic tract (STT). This study investigated response properties of contralaterally projecting STT neurons in C2 of the cat by the use of single-unit, microelectrode recordings. Standard antidromic stimulation and collision techniques were used to identify STT units projecting to the contralateral thalamus. Once an STT unit was found, its receptive field (RF) and responses to cutaneous stimuli such as touch, pressure, deep muscle squeeze, tap, noxious pinch, and heat were characterized. C2 units that were not activated from the contralateral thalamus (non-STT units) were also characterized. The locations of thalamic stimulation electrodes and spinal recording sites were reconstructed from electrolytic lesions. 2. A total of 48 STT and 68 non-STT units were well characterized. RF sizes were classified as small, intermediate, large, or whole body. Each unit was also classified as having one of two possible response types: simple units were those with homogeneous responses within the RF and were classified as low threshold (LT), high threshold (HT), wide dynamic range (WDR), deep, or tap. Complex units were those that responded differently in different regions of the RF. 3. The average depth of non-STT units subdivided by RF size was 2.1 +/- 0.6 (SD) mm for cells with small RFs, 2.4 +/- 0.8 mm for cells with intermediate RFs, 2.8 +/- 0.3 mm for cells with large RFs, and 2.7 +/- 0.5 mm for cells with whole-body RFs. The average depth of non-STT units based on response type was 2.0 +/- 0.5 mm for LT, 2.3 +/- 0.7 mm for HT, 2.1 +/- 0.7 mm for WDR, 2.6 +/- 0.9 mm for deep, 2.6 +/- 0.5 mm for tap, and 2.4 +/- 0.2 mm for complex. 4. A somatotopic organization along the rostrocaudal length of C2 and upper C3 was observed for non-STT units with small- and intermediate-size RFs. The average distance of the recording sites from the rostralmost dorsal rootlet of C2 was 3.8 +/- 2.1 mm for units with RFs on the face, 7.1 +/- 4.3 mm for units with RFs on the neck, and 11.9 +/- 5.1 mm for units with RFs on the forelimb. 5. The average threshold for antidromic activation of STT units was 175 +/- 120 microA. Most C2 STT units were activated from the ventroposterior region of the thalamus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

The location of spinothalamic axons within spinal cord white matter in cat and squirrel monkey.

The locations of spinothalamic (STT) fibers in the spinal cord white matter have been identified in cat and squirrel monkey by light-microscopic visualization of labeled fibers following multiple thalamic injections of wheatgerm agglutinin conjugated to horseradish peroxidase. Thalamic injections were combined with either a constricting dural tie or an intraspinal injection of colchicine to facilitate axonal labeling at more rostral spinal levels. In the cat, the ventral-to-dorsal distribution of labeled STT fibers was bimodal. In the ventrolateral white matter, labeled axons were coarse in nature and were primarily concentrated peripherally. In the dorsolateral white matter, labeled STT axons consisted of fine-caliber fibers concentrated in the ventral portion of the dorsolateral funiculus and were equally distributed throughout the medial and lateral white matter. In the squirrel monkey, the distribution of STT fibers was unimodal, extending from the ventral surface of the spinal white matter to the ventralmost portion of the dorsolateral funiculus. As in the cat, however, the ventrally located axons were large and coarse and were primarily located in the peripheral white matter, whereas the dorsalmost STT fibers were of fine caliber and were distributed equally in the medial and lateral white matter.

Animals

Ventrolateral and dorsolateral ascending spinal cord pathway influence on thalamic nociception in cat.

1. In cat there are two portions of the spinothalamic tract (STT)--a ventral component, the ventral spinothalamic tract (VSTT) made up of axons of cells of spinal cord laminae IV-X, and a dorsolateral component, the dorsolateral spinothalamic tract (DSTT) made up of axons of cells in lamina I of the spinal cord dorsal horn. This study was designed to evaluate thalamic neuronal responses to cutaneous noxious thermal stimuli and to determine the functional importance of pathways ascending in the ventral and dorsolateral portions of the spinal cord, ipsilateral to the thalamic recording site and contralateral to the hindlimb stimulation region, for transmission of nociceptive information to the thalamus. 2. Extracellular single-unit recordings were made from 45 neurons in the ventrobasal complex (VBX) of cat thalamus. Thirty-five of these units responded either exclusively or preferentially to noxious cutaneous stimuli. Responses to noxious thermal stimuli applied to the unit's receptive fields were obtained, and then the effects on these responses of blocking conduction through the dorsolateral funiculus (DLF) and the ventrolateral quadrant (VQ) of the thoracic spinal cord ipsilateral to the thalamic recording site were determined. DLF and VQ conduction blocks were accomplished with the use of a cold probe technique and, at times, surgical lesions of the appropriate portion of the spinal cord. 3. The nociceptive units were located in the periphery of the ventral posterior lateral nucleus (VPL) of the thalamus. Their locations corresponded to the somatotopic organization of VPL. Nociceptive thermal responses were found in both high-threshold (HT) (10 cells) and wide-dynamic-range (WDR) (22 cells) units. The receptive fields of these units were generally small and were located on the hindlimb contralateral to the recording site. The thermoreceptive units had thresholds between 44 and 48 degrees C and were able to code for stimulus intensity. 4. Nine of the 35 nociceptive units demonstrated a decrease in response and two units an increase in response to noxious cutaneous stimulation during DLF block ipsilateral to the recording site and contralateral to the cutaneous stimulation site, whereas four units demonstrated a decrease in response and one unit an increase in response to noxious thermal cutaneous stimulation during VQ block ipsilateral to the recording site and contralateral to the cutaneous stimulation site.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials

The spinothalamic tract.

The spinothalamic tract (STT) is made up of axons, originating from neurons in the spinal cord grey matter, which cross segmentally and then ascend to terminate in a variety of thalamic nuclei. The cells of origin of the STT are located throughout the spinal cord in three functional groups. Those located in lamina 1 of the spinal cord have small receptive fields and respond maximally to noxious peripheral stimulation. Those located in spinal cord laminae 4-6 have somewhat larger receptive fields and respond most commonly to both innocuous and noxious stimuli. The group originating in laminae 7-10 have large, frequently bilateral receptive fields and respond to a wide variety of cutaneous and deep stimuli. The largest concentration of STT neurons is found in the upper cervical spinal cord. The terminations of the STT in the thalamus include the lateral sensory thalamus, the intralaminar nuclei (primarily the centrolateral nucleus), and some of the medial nuclei (most prominently the medial dorsal nucleus). The cells located in laminae 1-6 project primarily to the lateral thalamus while the deeper STT neurons project primarily to the intralaminar and medial thalamus. An unique projection of lamina 1 cells to the nucleus submedius has been described. We hypothesize that the deep cells are related to many of the aversive aspects of pain while the more superficial STT cells are related to the sensory-discriminative aspects of pain.

Humans

Primate spinothalamic pathways: I. A quantitative study of the cells of origin of the spinothalamic pathway.

In six monkeys spinothalamic (STT) cells were retrogradely labeled by injecting 2% wheat germ agglutinin-conjugated horseradish peroxidase into the somatosensory thalamus. Following a 5-day survival period, the animals were perfused and the tissue was removed and processed with the tetramethyl benzidine technique. In all animals there were HRP-labeled STT cells in all segments of the spinal cord. In one old world monkey, the injection included most of the thalamus and resulted in 18.235 estimated total number of STT cells. Of this total, 35% were located in the upper cervical segments (C1-C3), 18% were located in C4-C8, 19% were in the thoracic spinal cord with most found in T1-T3; 6% were in L1-L3, 13% were in L4-L7, and 7% were in the coccygeal segments. Of the total labeled STT cells, 17% were found in the spinal cord ipsilateral to the thalamic injections; 53% of these cells were located in C1-C3 primarily in lamina VIII. The percentage of label found in the contralateral lower cervical region laminae I-III (43-50%), IV-VI (33-48%), and VII-X (8-17%) was similar among three animals with similar thalamic injections. The distributions of the shapes of the labeled STT cells were similar for each lamina between the lower cervical and lower lumbar regions. The mean diameter of the labeled STT cells varied with spinal cord segment and lamina. The lamina I STT cells were the smallest. In the cervical spinal cord, lamina VIII STT cells had the largest diameters, while in the lumbar region laminae IV-VI had the largest STT cells.

Animals

Primate spinothalamic pathways: II. The cells of origin of the dorsolateral and ventral spinothalamic pathways.

The cells of origin of the dorsolateral (DSTT) and the ventral (VSTT) spinothalamic tracts were studied in 11 monkeys. The spinothalamic tract cells were retrogradely labeled by horseradish peroxidase (HRP) injected in the thalamus. All animals also received a midthoracic spinal cord lesion on the side ipsilateral to the thalamic injections. The distribution of labeled cells found in these animals throughout the cervical segments was similar to animals with no spinal cord lesions. Five animals had ventral quadrant lesions to demonstrate the cells of origin of the DSTT. In macaques with complete ventral quadrant lesions, more than 80% of the HRP label in the contralateral L4-L7 segments was located in lamina I, while in squirrel monkeys, the label in the contralateral lower lumbar region was distributed between laminae I-III and IV-VI. Few labeled cells were found in laminae VII-X. Six animals received dorsolateral funiculus lesions to demonstrate the cells of origin of the VSTT. In animals with adequate lesions, 84-99% of the contralateral HRP label in L4-L7 was located in laminae IV-X. Macaques had a larger percentage of labeled cells located in lamina I than squirrel monkeys. The results indicate the existence of two spinothalamic pathways in the primate. The DSTT was calculated to compose about one fourth of the total spinothalamic population.

Animals

Primate spinothalamic pathways: III. Thalamic terminations of the dorsolateral and ventral spinothalamic pathways.

The termination sites of the dorsolateral (DSTT) and ventral (VSTT) spinothalamic pathways were determined by using anterograde transport of horseradish peroxidase from the lumbar spinal cord in primates. One animal had no spinal cord lesion, while of two other animals, one received a midthoracic dorsolateral funiculus lesion, and the other received a midthoracic ventral quadrant lesion contralateral to the injection. The thalamic label in the animal with no spinal cord lesion was much less than the label in the two animals with spinal lesions. Moreover, in the animals with spinal lesions, HRP-labeled cells were found within the thalamus. Therefore, the remaining six animals received ipsilateral hemisections and bilateral dorsal column lesions, irrespective of the contralateral lesions. The thalamic label in the animals without contralateral lesions were assumed to represent the total spinothalamic input to the diencephalon. In these animals, label was located mainly in suprageniculate and pulvinar oralis, caudal and oral divisions of ventral posterior lateral nucleus, the lateral half of ventral posterior inferior nucleus, and zona incerta, while in the medial thalamus label was primarily in two distinct bands in medial dorsal nucleus and in the posterior dorsal portion of central lateral nucleus. Scattered lighter labeling was found in other thalamic nuclei. The pattern of terminal labeling observed in the ventral posterior lateral region was arranged in patches, while elsewhere in the thalamus a more uniform labeling pattern was observed. The thalamic label in animals with contralateral ventral quadrant lesions represented the terminations of the DSTT, while the label in animals with contralateral dorsolateral funiculus lesions represented VSTT terminations. The labeling pattern was similar between these two groups. However, there were small differences between them. These results indicate that DSTT and VSTT terminations largely overlap and innervate the lateral and medial thalamamus.

Animals

A cryogenic device for reversibly blocking transmission through small regions of the spinal cord white matter.

A simple cryogenic device is described. This device is capable of cooling neural tissue in contact with the probe and maintaining the tissue at the desired temperature for extended periods of time. The cold probe can thereby reversibly block neural transmission through small portions of the spinal cord white matter. Interruption of axonal transmission is achieved by placing the tip of the device in contact with the exposed surface of the spinal cord and cooling the tip of the probe to -1 to +2 degrees C. The investigator monitors the tip temperature and adjusts the pump rate to maintain a constant tip temperature. The cross-sectional area under the probe where effective transmission block is achieved is about 1.5 mm2 which approximates the size of a single funiculus in the cat thoracic spinal cord. The cryogenic device was constructed for less than $700. The properties of this device were studied in physiologic experiments in cats. This device reversibly, selectively and repeatedly blocked the ascending mass action potential in the dorsolateral funiculus, transmission through ascending spinal axons in the dorsal columns, transmission through axons of spinal dorsal horn cells, the descending inhibitory input to the dorsal horn and the activity of thalamic nociceptive neurons. The reversible cold block effects on single units were observed for the duration of the experiments (up to 18 h) with no detectable damage to the underlying tissue. The physiologic effects of the cold block were usually reversed a few minutes after rewarming, although in some cases it took up to 40 min for the complete reversal of the cold block. This cryogenic device is useful for studying spinal cord pathways.

Animals

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.

Animals

Activation of carotid sinus baroreceptors reduces pain sensations evoked by electrical and cold stimulation of human teeth.

Activation of carotid sinus baroreceptors (CSBs) has been shown to have an influence on the perception of pain evoked by electrical stimulation of the skin. The present work was carried out to study to what extent dental pain can be modulated by simultaneous activation of CSBs. In 19 healthy voluntary human subjects, activation of CSBs was induced by application of negative pressure to an air tight collar fitted around the neck of the subjects (neck suction). Dental pain was evoked by electrical stimulation of the tooth (determination of the pain threshold) and by cold stimulation of teeth (ratings of the pain intensity). Neck suction resulted in an elevation of the dental pain thresholds and a reduction of the ratings of the cold-evoked dental pain. The present findings support the suggestion of the interaction of cardiovascular control systems with trigeminal nociceptive systems.

Adult

The spinothalamic tract: an examination of the cells of origin of the dorsolateral and ventral spinothalamic pathways in cats.

The locations of spinothalamic neurons and the funicular trajectories of their axons were studied in cats by retrograde transport of horseradish peroxidase (HRP). Five animals were used as controls to determine the cervical and lumbar laminar distributions of neurons contributing to the spinothalamic tract. An additional eight animals were used to determine the funicular trajectories of the spinothalamic axons of lumbar neurons by utilizing a series of thoracic spinal cord lesions in conjunction with retrograde transport of HRP from the sensory thalamus. Three of these animals underwent midthoracic ventral quadrant lesions, four animals underwent midthoracic dorsolateral funiculus lesions, and one animal underwent total spinal cord transection sparing the dorsal columns. The locations of the cells containing the HRP reaction product were then determined after a 3- to 5-day survival time, and the patterns of labeled cell locations of the lesion groups were compared to the control group patterns. In the lesioned animals, the cervical spinothalamic cell locations were used as a control to confirm the uniformity of the injection sites, transport and tissue processing. The major finding of this study is that there exist two distinct components of the spinothalamic tract. The dorsolateral spinothalamic tract (DSTT) is made up of axons originating in contralateral spinal cord lamina I and has negligible contribution from the deeper spinal cord laminae. The axons of lamina I cells cross segmentally and ascend exclusively in the dorsolateral funiculus (DLF). The DSTT comprises approximately 25% of the total spinothalamic input from the lumbar enlargement. The ventral spinothalamic tract (VSTT) is made up of axons originating in spinal cord laminae IV-V and VII-X. Very few lamina I cells contribute axons to the VSTT. This crossed pathway ascends in the ventrolateral and ventromedial portions of the spinal cord. No cells contributing to the spinothalamic tract were identified in spinal cord segments caudal to a dorsal column sparing lesion, indicating that there are no spinothalamic tract axons traveling in the dorsal columns. These results expand the classical concept of information processing by the spinothalamic tract. The DSTT is made up of lamina I cell axons. All lamina I spinothalamic cells respond exclusively to noxious peripheral stimuli. Hence the DSTT is a major nociceptive-specific ascending spinal pathway, yet lies outside the confines normally assigned to the spinothalamic tract.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Inhibition of dorsal-horn cell responses by stimulation of the Kölliker-Fuse nucleus.

The Kölliker-Fuse nucleus (KF) in the dorsolateral pons has been shown to be the major source of catecholamine innervation of the spinal cord. This has important implications in terms of pain control mechanisms, since catecholamine-mediated mechanisms are essential for the expression of opiate and other varieties of antinociception. This study examines the effects of KF stimulation on responses of dorsal-horn cells to innocuous and noxious cutaneous stimuli in anesthetized cats. Stimulation of the KF potently inhibits the responses of dorsal-horn cells to both noxious and innocuous stimuli. The threshold for the inhibitory effect is significantly lower for responses to noxious stimuli as opposed to innocuous stimuli. The inhibitory effect is specific to the stimulus site, as evidenced by a marked decrease in the effect following small changes in the position of the stimulating electrode in the brain stem. The latency of the effects indicates a bulbospinal conduction velocity of 4 to 5 m/sec, which is much slower than usual reticulospinal effects and is consistent with a catecholamine-mediated system. The dependence of KF-spinal inhibition on intact biogenic amines was tested by depleting the animals of these amines with reserpine pretreatment. Depletion of biogenic amines resulted in a significant decrease in the KF spinal inhibitory effects, suggesting their dependence on intact noradrenergic stores. The results of these studies are consistent with the idea that the KF-spinal system plays an important noradrenergic-dependent role in the brain-stem modulation of spinal processing of noxious, potentially painful stimuli.

Animals

Funicular course of catecholamine fibers innervating the lumbar spinal cord of the cat.

The purpose of this study was to determine the funicular location of descending catecholamine (CA) fibers innervating the lumbar spinal cord from the dorsolateral pons (DLP). The locations of catecholamine-containing cell bodies which project to the lumbar spinal cord were determined by combining the use of the retrogradely transported fluorescent dye, Evans Blue (EB), with the glyoxylic acid histofluorescence technique. Lumbar injections of Evans Blue were combined with thoracic lesions of the dorsolateral funiculi (DLF) or ventrolateral funiculi (VLF) in order to retrogradely label those CA-containing or non CA-containing cell bodies whose axons descend within the spared hemispinal cord. By this technique it was determined that descending CA fibers innervating the lumbar spinal cord of the cat project through both the DLF and the VLF. The nucleus subcoeruleus, the Kolliker-Fuse nucleus and the CA cell bodies in the area of A5 each contain a significant number of CA-containing cells whose fibers descend both within the DLF and the VLF, while the nucleus locus coeruleus projects to the lumbar cord primarily through the VLF. Catecholamine cells of the DLP innervate the lumbar spinal cord bilaterally, although there is an ipsilateral predominance. The CA-containing cells of the DLP which innervate the contralateral spinal cord were shown by ipsilateral or contralateral thoracic hemisection to decussate both above and below the thoracic lesion. Non-CA-containing cells from the DLP also crossed at all levels of the spinal cord; however, cells from the caudal pons had a larger number of cells which crossed above the thoracic lesion while cells of the more rostral pons had a larger number of cells which crossed below the lesion.

Animals

A dorsolateral spinothalamic pathway in cat.

A spinothalamic tract that courses in the dorsolateral funiculus of the spinal cord and originates almost exclusively from spinal lamina I neurons has been demonstrated in the cat by retrograde transport of horseradish peroxidase. This tract is of special interest because the course of this predominantly lamina I, contralateral projection lies outside the classical course of the spinothalamic tract and because most lamina I cells contributing to the spinothalamic tract have been shown by other investigators to respond exclusively to somatic noxious stimuli. This newly described tract has important implications in the processing of noxious stimuli.

Animals