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Biomedical subjects

J M Chung

Publications and source records attributed to J M Chung.

At least 109 records · Page 6Linked to original sources

Funicular trajectories of brainstem neurons projecting to the lumbar spinal cord in the monkey (Macaca fascicularis): a retrograde labeling study.

Brainstem nuclei projecting to the lumbar spinal cord in the monkey were identified by using horseradish peroxidase and the fluorescent dye granular blue. These retrogradely transported tracers were used in fluid and/or gel forms to determine the funicular trajectories of the brainstem-spinal projections. The major descending components of the dorsal funiculus arose from the n. gracilis, n. cuneatus, and the n. of the solitary tract. Major components of the dorsolateral funiculus (DLF) came from the raphe complex, medullary and pontine reticular formation, locus coeruleus, Edinger-Westphal n., and red n. Other nuclei giving rise to minor contributions to the DLF included n. gracilis, n. cuneatus, n. of the solitary tract, medial and spinal vestibular n., subcoeruleus, periaqueductal gray, interstitial n. of Cajal, n. of Darkschewitsch, and the anteromedian n. The major components of ventral cord paths (ventrolateral and ventral funiculi) arose from the raphe complex, the medullary and pontine reticular formation, lateral and spinal vestibular n., and the coerulean complex. Minor contributions to the ventral paths descended from the dorsal motor n. of X, n. of the solitary tract, medial vestibular n., paralemniscal reticular formation, dorsal parabrachial n., n. cuneiformis, periaqueductal gray, Kölliker-Fuse n., and red n. The possible functional implications of the funicular distribution of these descending pathways are discussed from the perspective of descending inhibition and pain modulation.

Afferent Pathways↗

Electrophysiological evidence for the presence of fibers in continuity between dorsal and ventral roots in the cat.

Action potentials were recorded from the L7 or S1 dorsal root of the cat following stimulation of the peripheral end of the cut ventral root of the same segment. Conversely, action potentials were also recorded from the ventral root while stimulating the peripheral end of the cut dorsal root. Based on the conduction velocities of 52 single fibers, one-third were A delta-fibers and the remaining two-thirds belonged to the C-fiber category. These results suggest that there are both A- and C-fibers in continuity between the dorsal and the ventral root.

Animals↗

Effects of capsaicin applied to a peripheral nerve on the responses of primate spinothalamic tract cells.

Capsaicin is a neurotoxin that appears to affect unmyelinated nociceptive sensory fibers selectively. We examined the effects of capsaicin applied topically to the sural nerve on peripheral nerve volleys and on the responses of neurons belonging to the spinothalamic tract (STT) in the monkey. The responses examined included those following electrical stimulation of the sural nerve and also those produced by more natural forms of noxious and innocuous stimuli applied to the skin. Capsaicin (1% solution) applied onto the sural nerve for 15 min resulted in a reduction of the sizes of A delta- and C-fiber afferent volleys. These changes paralleled the reduction of A- and C-fiber responses of the STT cells elicited by electrical stimulation of the sural nerve. During capsaicin application onto the sural nerve, the background activity of STT cells increased for 5-10 min. After capsaicin treatment, the responses of STT cells to innocuous mechanical stimuli applied to the cutaneous receptive field were increased, whereas the responses to noxious mechanical stimuli were decreased. However, topical capsaicin application almost eliminated the responses of STT cells to noxious heat stimuli. The results of the present study suggest that topical capsaicin application onto a peripheral nerve produces a transient nociceptive response followed by a decrease in sensitivity to noxious stimuli, particularly to noxious heat. These changes are due to conduction block of the nerve fibers at the site of capsaicin application.

Animals↗

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)

Animals↗

Inhibition of primate spinothalamic tract cells by TENS.

Transcutaneous electrical nerve stimulation (TENS) was applied in an experimental animal model to investigate the underlying mechanisms of this treatment. Recordings were made from identified spinothalamic tract (STT) neurons in the lumbosacral spinal cords of seven anesthetized monkeys. The STT cells were activated by stimulating the common peroneal nerve at a suprathreshold intensity for C-fibers. Evoked responses of C-fibers were compared before, during, and after application of TENS for 5 minutes from a commercially available TENS unit. The current delivered by the TENS unit was monitored. In 14 STT cells, some degree of inhibition of C-fiber evoked responses occurred only when the intensity of TENS exceeded the threshold of A delta fibers. At a given stimulus intensity, bursts of pulses repeated at a low rate were more effective than high-rate pulses. When TENS was applied to an area of the skin within a cell's receptive field, it was more effective than when it was applied outside the receptive field. The C-fiber volley recorded from a peripheral nerve was not reduced in size, and there were no substantial changes in its latency due to TENS. The inhibition of the activity of STT cells was not altered appreciably after intravenous injection of naloxone hydrochloride. These results suggest that TENS produces central nervous system inhibition by activating A delta afferent fibers. The inhibitory effects of TENS on STT cells appear to be due to a mechanism that does not involve release of endogenous opioid substances.

Animals↗

Segmental distribution of dorsal root ganglion cells with axons in the inferior cardiac nerve.

The segmental distribution of visceral afferent neurons with axons in the cardiac nerve was studied in cats with the horseradish peroxidase (HRP) technique. After HRP was introduced into the left inferior cardiac nerve, labeled dorsal root ganglion cells were found in the ganglia from the C7 to T7 spinal levels, with a wide variation in distribution among the individual animals. An average of 93 cells was labeled per animal. The data indicate that the afferent nerve fibers in the inferior cardiac nerve project to a much wider range of segments of the spinal cord than previously believed.

Animals↗

The effects of small doses of barbiturate on the activity of primate nociceptive tract cells.

The activity of neurons identified as or similar to spinothalamic tract cells was compared in anesthetized, intact monkeys and in unanesthetized, decerebrate or spinalized animals. Background activity and responses to A- and C-fiber volleys were smaller in decerebrate than in the other preparations, suggesting the presence of a tonic descending inhibition of nociceptive tract cells in the decerebrate state. Injections of small doses of sodium pentobarbital caused a slight increase in sensitivity of peripheral receptive fields to mechanical stimuli in some cells, and an increase in responses to squeezing the skin with forceps and to C-fiber volleys. Larger doses of pentobarbital reduced the responses to A- and C-fiber volleys. These observations suggest that the activity of nociceptive tract cells is well preserved in the presence of the doses of pentobarbital we routinely use and are consistent with the hyperalgesic state reported to be produced by small doses of barbiturate.

Anesthesia, General↗

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

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

Animals↗

Factors influencing peripheral nerve stimulation produced inhibition of primate spinothalamic tract cells.

Several factors that influence the inhibition of primate spinothalamic tract (STT) cells produced by repetitive peripheral conditioning stimulation have been studied. Identified STT cells were recorded from the lumbosacral spinal cord in intact, anesthetized monkeys. In addition, presumed STT cells were recorded from unanesthetized, decerebrate or decerebrate, spinalized monkeys; these cells were identified by antidromic activation from the contralateral ventral lateral funiculus of the upper cervical spinal cord. Activity of the STT cells was evoked by electrically stimulating the sural nerve with pulses having an intensity strong enough to activate C fibers. The C fiber evoked STT cell activity was compared before, during and after repetitive conditioning stimuli applied to the tibial nerve for 5 min. By applying repetitive strengths of conditioning stimuli, it was found that the A delta fiber group is the most important for producing inhibition of STT cells, although significant additional effects were also produced by the A alpha beta and C fiber groups. Conditioning stimuli with fixed intensity at different frequencies showed that the higher the frequency the more powerful the inhibition within the range we tested (0.5-20 Hz). The inhibition produced by peripheral nerve stimulation was segmentally organized, so the most effective nerve in producing inhibition amongst those tested was the ipsilateral tibial nerve. The contralateral sciatic nerve, the ipsilateral median nerve and the contralateral median nerve were less effective in that order. The results of the present experiments suggest that the most effective way to produce analgesia by peripheral nerve stimulation would be by high frequency stimulation of a nerve innervating the area from which pain originates with an intensity at least strong enough to activate A delta fibers.

Animals↗

Effects of iontophoretically released amino acids and amines on primate spinothalamic tract cells.

The effects of glutamate (Glu), gamma-aminobutyric acid (GABA), glycine (Gly), serotonin (5-HT), norepinephrine (NE), dopamine (DA), and acetylcholine (ACh) were examined in this study by iontophoretic application onto primate spinothalamic tract (STT) neurons identified antidromically by stimulation in the contralateral thalamus. Drugs were tested for effects on background activity, Glu-induced firing, and activity evoked by pinching of the skin. Whereas Glu excited STT cells and was thus used for tests of the other compounds, the amino acids GABA and Gly inhibited Glu- and pinch-induced activity in all STT cells examined. STT cells were also inhibited by 5-HT, NE, and DA. Only two cases of excitation by 5-HT were seen (of 58 cells tested). ACh also had inhibitory actions on STT cells, although 3 of 21 cells exhibited some enhancement of activity. The effects of these compounds on identified STT cells resemble previous demonstrations of the effects of these drugs on dorsal horn interneurons. The results suggest that GABA, Gly, 5-HT, NE, and DA may be inhibitory neurotransmitters on nociceptive STT cells.

Acetylcholine↗

Effects of iontophoretically released peptides on primate spinothalamic tract cells.

The peptides substance P (SP), methionine-enkephalin (M-ENK), leucine-enkephalin (L-ENK), and cholecystokinin (CCK) were released iontophoretically near spinothalamic tract (STT) cells in anesthetized monkeys and STT-like cells in decorticate, spinalized monkeys. Peptide effects were observed on background discharges, firing induced by release of glutamate, and activity evoked by pinching the skin. SP could have any of several actions on STT cells, including excitation, inhibition, or biphasic effects. Multiple effects often resulted while recording from an individual cell when the dose or the electrode position was changed. M-ENK and L-ENK generally inhibited STT cells, and in some cases it was possible to demonstrate a reversal of the inhibition by naloxone. CCK also caused an inhibition that was additive with that produced by L-ENK. The multiple actions of SP on STT cells suggests the possibility that there may be more than one type of SP receptor on STT cells, although alternative explanations should be considered. Inhibition of STT cells by M- and L-ENK is consistent with the known analgesic action of opiates through spinal cord mechanisms. CCK has an action on STT cells similar to that of the enkephalins.

Action Potentials↗

Activation of central neurons by ventral root afferents.

It is a fundamental principle of vertebrate neuronal organization that sensory fibers are restricted to dorsal roots and motor fibers to ventral roots. Recent evidence, however, indicates that there are many sensory fibers in ventral roots. The present report shows that stimulation of these fibers activates neurons in the dorsal horn. This provides evidence at the single-cell level for the importance of ventral root afferents and provides an explanation for the clinical phenomenon of recurrent sensibility.

Animals↗

Midbrain nuclei projecting to the medial medulla oblongata in the monkey.

To identify the midbrain nuclei that project to the medial part of the lower brainstem in the monkey, labeled cells were mapped in the midbrain following the injection of horseradish peroxidase into the medial medulla oblongata. After the general distribution of labeled cells was observed in three animals with large injections, more discrete injections of HRP were made in different locations in six additional animals. The small injections were centered in the nucleus raphe magnus, nucleus reticularis gigantocellularis, or nucleus medullae oblongatae centralis. The five labeled midbrain nuclei were the periaqueductal gray, nucleus cuneiformis, deep layers of the superior colliculus, nucleus of Darkschewitsch, and the interstitial nucleus of Cajal. In addition, the parvocellular division of the red nucleus and the posterior pretectal nucleus contained large numbers of cells when the injection spread into the inferior olive. No major differences in the distribution of labeled cells between different injection sites were found with the exception that the superior colliculus did not contain any labeled cells when the injection was restricted to midline structures. The functional implications of these anatomical findings are discussed in relation to the descending control of pain.

Animals↗

Cells of origin of the spinoreticular tract in the monkey.

The distribution of the cells of origin of the primate spinoreticular tract was determined following injections of horseradish peroxidase (HPR) into the pontomedullary reticular formation in Macaca fascicularis. Five animals received large bilateral injections which included the raphe nuclei and seven monkeys received smaller, unilateral injections. Sections sampled were from upper cervical levels, the cervical enlargement, upper and lower thoracic levels, and lumbosacral levels. The laminar distribution of spinoreticular cells in all spinal cord levels was comparable. More than half of the labeled cells were located ventromedially, in laminae VII and VIII. HRP-labeled cells were also found in the dorsal horn, primarily in the lateral reticulated part of lamina V. Some cells were also found in laminae I and X. Spinoreticular cells in the lumbosacral spinal cord mainly projected to the contralateral brainstem. In the cervical enlargement, however, a bilateral distribution of cells was observed following unilateral injections of HRP. Most spinoreticular cells were multipolar neurons with extensive dendritic ramifications. The distribution of spinoreticular cells is similar to the distribution of spinal cord neurons that project to the medial thalamus, but different from that of spinal neurons projecting to the ventrobasal complex. The anatomical organization of the spinoreticular tract is consistent with a role for this pathway in nociception.

Animals↗

Facilitation of the response of primate spinothalamic cells to cold and to tactile stimuli by noxious heating of the skin.

Spinothalamic tract cells in anesthetized monkeys were found to respond to noxious cold stimuli (18/19 cells tested), as well as to noxious heat and noxious mechanical stimuli. Responses to repetition of the noxious cold stimuli after a series of noxious heat stimuli were enhanced. However, subtraction of the enhanced background activity that resulted from damage of the skin revealed that the enhanced response to noxious cold stimuli were due to superposition of the original responses upon an enhanced background activity, rather than to sensitization of the responses to noxious cold stimuli per se. Furthermore, the responses to innocuous mechanical stimuli applied either within the area that was damaged or outside this area were enhanced, provided the noxious heat was applied for a long enough time. Thus, damage to a region of skin can result in enhanced responsiveness of spinothalamic cells to stimuli applied in an undamaged region of the receptive field. The possible relationship between these observations and cutaneous hyperalgesia is discussed.

Animals↗

Primary afferent axons in the tract of Lissauer in the monkey.

The main thrust of the present study was to determine the numbers of primary afferent fibers in the tract of Lissauer in the monkey. The findings are that approximately 40% of the axons in the tract of Lissauer are primary afferent axons from a single segment, and approximately another 40% are primary afferents from segments cranial and caudal to the segment under consideration. Presumably, the remaining 20% are propriospinal axons. There is relatively little difference in the proportions of primary afferents in medial as opposed to lateral parts of the tract, and in this respect the monkey differs somewhat from the rat and cat. Thus in the monkey the tract of Lissauer should probably be regarded as a primary afferent pathway with the propriospinal forming a distinct but relatively minor component of the tract.

Afferent Pathways↗

Ascending spinal pathways mediating somato-cardiovascular reflexes.

The influence of spinal somatic afferent pathways upon cardiovascular parameters were studied in anesthetized and conscious dogs. Previous studies on anesthetized cats indicated that activation of somatic A afferent fibres results in a depressor response mediated by ascending spinal pathways in the dorsolateral funiculus (DLF). Additional activation of somatic C afferent fibers results in a pressor response mediated by pathways in the region of the dorsolateral sulcus (DLS). In anesthetized dogs sympathetic-mediated cardiovascular responses to somatic afferent stimulation are found to be conducted in the DLS. To test the possibility that these afferent pathways may mediate cardiovascular responses to exercise, dogs instrumented for blood pressure and heart rate monitoring were trained to run on a treadmill on all 4 legs and on their hindlegs only. Lesions on the DLS and a portion of the DLF significantly altered heart rate responses to treadmill running on all 4 legs. These data suggest that somato-autonomic reflexes participate in the cardiovascular adjustments which occur during exercise.

Afferent Pathways↗