Inhibition of nociceptive and nonnociceptive responses of primate spinothalamic cells by stimulation in medial brain stem.
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Animals↗
Biomedical subjects
J M Chung
Publications and source records attributed to J M Chung.
Inhibition and excitation of primate spinothalamic tract neurons by stimulation in region of nucleus reticularis gigantocellularis.
1. Electrical stimulation in the region of the nucleus reticularis gigantocellularis (NGc) in anesthetized monkeys inhibited or excited spinothalamic tract neurons in the lumbosacral and cervical enlargements. 2. The descending effects were generally more pronounced for activity evoked by cutaneous A-delta-fibers than for activity produced by large myelinated cutaneous afferents. Nevertheless, the responses to all types of natural stimuli used could be inhibited or facilitated. 3. The excitation from repeated brief stimulus trains to the NGc sometimes increased progressively, suggesting the existence of a positive feedback system. Occasionally, repeated stimulation of the NGc produced a progressively greater inhibition. 4. The threshold stimulus strength to elicit the inhibitory and excitatory actions was usually less than 50 microA, and in some cases less than 25 microA. The inhibition and excitation increased as the stimulus intensity was raised above the threshold value, or as the number and/or frequency of pulses in the stimulus train was increased. 5. The strongest inhibition and excitation was produced by stimulation within the NGc on either side of the brain stem. There was no obvious topographic organization of inhibitory and excitatory zones. 6. Dorsolateral tractotomies in the high cervical spinal cord did not prevent the effects of NGc stimulation, indicating that the inhibitory and excitatory pathways descend in the ventral parts of the white matter. 7. It is suggested that the inhibition and excitation are mediated by the medullary reticulospinal system.
Animals↗
Cat phrenic nucleus architecture as revealed by horseradish peroxidase mapping.
Cat phrenic motoneurons, labeled by intradiaphragmatic injection of horseradish peroxidase, formed a tight cluster in the most ventral portion of the ventral horn in lamina IX of the lower cervical cord. Cell counts were symmetrically distributed for 17 to 21 mm along the longitudinal axis of the cord with a unimodal peak at the junction of segments C5 and C6. The phrenic nucleus was bilaterally organized on either side of the cord with anatomical symmetry and in no case was there evidence for the crossing of phrenic axons in the cord. Assessment of cellular geometry and intercellular relationships demonstrated that phrenic cell diameters approximated a normal distribution with a single peak at 26 mum while longitudinal cell lengths average 76 mum. Cells of different size were mixed randomly at all levels of the nucleus. The minimum distance between cells was about 10 mum and the maximum cell packing density approached 2 cells per 10(6) mum3. The results confirm the location of the cat phrenic nucleus, extend the knowledge of phrenic motoneuronal geometry, and provide an anatomical basis for the understanding of recruitment and synchronization phenomena within the phrenic nucleus.
Animals↗
Sympathetic neurons in the cat spinal cord projecting to the stellate ganglion.
Horseradish peroxidase (HRP) was injected into the stellate ganglia of anesthetized cats. After a 2-day survival time the spinal cord was processed for the HRP reaction to study the distribution of the preganglionic neurons which project to the stellate ganglia. HRP-labeled neurons in the cord were located exclusively on the side ipsilateral to the injected stellate ganglia and were concentrated in four distinct areas: (1) intermediolateral cell column (78.2%), (2) lateral funiculus (18.5%), (3) intercalated area and (4) central autonomic area (3.3%) for the latter 2 areas). Their distribution pattern in the very rostral pole of the thoracic sympathetic preganglionic cell column was different from the typical thoracic pattern in that a greater proportion of the cells were located in the lateral funiculus, and a few labeled cells were observed in the ventral horn. Longitudinally, a wide range (C8-T8) of spinal cord levels projected to the stellate ganglia, with a peak at the T2 level. These observations infer that a large population of axonal processes of sympathetic preganglionic neurons traveled several segments of the spinal cord through an intraspinal pathway before exiting a particular ventral root.
Animals↗
Ascending spinal pathways for the somatosympathetic A and C reflexes.
Sympathetic unit nerve activity was recorded from the cervical sympathetic trunk of anesthetized, vagotomized, and carotid sinus-denervated cats. Single pulses or short trains of pulses with suprathreshold intensity for afferent C fibers were applied to the common peroneal nerve to elicit somatosympathetic A or simultaneous A and C reflexes, respectively. Bilateral lesions of an ascending spinal pathway in the dorsolateral sulcus area (DLS) of the T12 spinal cord eliminated the sympathetic C reflex. The remaining somatosympathetic A reflex was abolished by the subsequent lesion of an ascending spinal pathway in the dorsolateral funiculus (DLF) bilaterally. The duration of the silent period was found to be mainly influenced by an ascending spinal pathway in the DLF. It was concluded that excitation of afferent A fibers activates ascending pathways mainly in the DLF and a smaller contribution in the DLS of the spinal cord. This produces a small reflex excitation (A reflex) followed by a long silent period in the sympathetic nerves resulting in a net decrease of total sympathetic nerve activity. On the other hand, excitation of afferent C fibers activates the ascending spinal pathway in the DLS. This produces a reflex excitation (C reflex) which exceeds the decreased activity due to the silent period resulting in a net increase of total sympathetic nerve activity.
Action Potentials↗
Excitation of primate spinothalamic neurons by cutaneous C-fiber volleys.
1. The responses of spinothalamic tract cells in the lumbosacral spinal cords of anesthetized monkeys were examined following electrical stimulation of the sural nerve or the application of noxious thermal and mechanical stimuli to the skin on the lateral aspect of the foot. 2. The spinothalamic tract neurons were classified as wide dynamic range (WDR), high-threshold (HT), or low-threshold (LT) cells on the basis of their responses to mechanical stimuli. 3. All of the WDR and HT spinothalamic tract cells tested responded to volleys in A- and C-fibers. However, strong C-fiber responses were more common in HT than in WDR cells. 4. The responses atributed to C-fibers were graded with the size of the C-fiber volley. The latencies of the responses attributed to C-fibers indicated that the fastest afferents involved had a mean conduction velocity of 0.9 m/s. The responses remained after anodal blockade of conduction in A-fibers. 5. Temporal summation of the responses of spinothalamic tract cells was demonstrated both to brief trains of stimuli at 33 Hz and to single stimuli repeated at 1- to 2-s intervals. The latter phenomenon is often called "windup." 6. The responses of several spinothalamic tract cells to noxious heat pulses could still be elicited during anodal blockade of conduction in A-fibers. Similarly, it was possible to demonstrate an excitatory action of noxious mechanical stimuli despite interference with conduction in A-fibers by anodal current. 7. The cells investigated were located either in the marginal zone or in the layers of the dorsal horn equivalent to Rexed's laminae IV-VI in the cat. The cells were generally activated antidromically from the caudal part of the ventral posterior lateral nucleus of the thalamus.
Animals↗
Responses of primate spinothalamic neurons to graded and to repeated noxious heat stimuli.
1. The responses of primate spinothalamic tract cells innervating the glabrous skin of the foot to noxious thermal stimuli have been examined. 2. Of the 41 cells studied, 98% responded to noxious thermal stimuli. Heating the cutaneous receptive field with a series of stimuli from 35 to 43, 47, and 50 degrees C produced a graded increase in discharge rate. The responses were characterized by an onset, which occurred after the temperature change had either slowed or stopped, an acceleration in the discharge up to a peak, and then an adaptation to a new base-line level. The time constants of adaptation were faster than those reported for C polymodal nociceptors. 3. No systematic differences were found in the responses to noxious thermal stimuli of cells with wide dynamic range receptive fields and of cells with narrow dynamic range, high-threshold receptive fields. There were also no differences in the responses of cells located in the marginal zone and of cells located in the neck of the dorsal horn. 4. The relationship between peak frequency and final skin temperature with a 30 s stimulus duration can best be described by a power function with an exponent of 2.1. An increase in the stimulus duration to 120 s resulted in an increase in the exponent of the power function to 3.2. 5. Repetition of the series of 30-s heat stimuli resulted in an increase in peak frequency, total impulse count, and background activity. Repetition of stimuli having a duration of 120 s produced an increase in the peak frequency at 43 and 45 degrees C, a smaller increase at 47 degrees C, and a decrease at 50 degrees C. Background activity was increased by the lower temperature stimuli, but was decreased following higher temperature stimuli. 6. In six additional cells, the skin was heated with three consecutive presentations at each temperature level (43, 45, 47, and 50 degrees C) for 30 s. No change was observed in the peak frequencies of the responses to successive stimuli of the same intensity. However, the exponent of the power function relating the average peak frequency for the six cells to changes in skin temperature was 3.9. This exponent was larger than that seen when two series of graded heat stimuli of 120 s duration were used, indicating more sensitization despite the fact the total time of exposure to noxious heat was less. 7. A role for both high-threshold and wide dynamic range spinothalamic cells in transmitting nociceptive information to the diencephalon is postulated.
Adaptation, Physiological↗
The anatomical localization of descending pressor pathways in the cat spinal cord.
Functional evidence suggests the location of descending pressor pathways in the bilateral dorsolateral funiculus (DLF). To investigate the anatomical course of these pathways, orthograde degeneration studies were conducted following unilateral lesions of the DLF at the C6-C7 spinal level. Degenerating fiber tracts were localized exclusively in the ipsilateral DLF. Degeneration was also demonstrated in the central portion of the intermediate spinal gray matter, but little or no degeneration in the intermediolateral cell column. This evidence suggests that these descending pathways do not terminate on sympathetic preganglionic cell bodies or their proximal dendrites, but perhaps upon their more distal dendrites or interneurons.
Animals↗
Neurophysiological evidence for spatial summation in the CNS from unmyelinated afferent fibers.
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Afferent Pathways↗
Ascending pressor and depressor pathways in the cat spinal cord.
Blood pressure responses to stimulation of the cervical dorsolateral sulcus (DLS) of the spinal cord and lumbar dorsal roots were studied in anesthetized, vagotomized, and paralyzed cats. Stimulation of the lumbar dorsal roots elicited pressor responses with high-frequency stimulation (50 Hz, 10 V, 1 ms) and depressor responses with low-grequency stimulation (1 Hz, 10 V, 1 ms). Pressor responses were converted to depressor responses after bilateral lesions were made in the DLS area rostral to the site of stimulation. These results suggest that the ascending spinal pressor pathways are localized in the DLS region. Furthermore, these depressor responses were abolished by placing additional bilateral lesions in the dorsolateral funiculus (DLF) rostral to the site of stimulation. These data indicate the presence of ascending depressor pathways in the DLF which are anatomically separate from pressor pathways. Both pathways were found to be bilateral systems, and decussation of fibers appears to be complete within three segments rostral to their entry into the spinal cord. Ascending depressor pathways have a low optimal frequency of activation, as opposed to the ascending pressor pathways which have a relatively high optimal frequency of activation. Neurophysiological evidence obtained by recording unit activity from the cervical sympathetic trunk confirmed the localization of the ascending pressor and depressor pathways.
Animals↗
Sympathetic preganglionic neurons of the cat spinal cord: horseradish peroxidase study.
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Animals↗
Effect of isolated head heating and cooling on sweating in man.
A double climate chamber which permitted the independent regulation of temperature in each chamber was used to produce isolated head heating and cooling in three subjects. Deep body temperature was recorded from the tympanic membrane, oral cavity, esophagus, and rectum. Skin temperature was measured on nine body regions and a weighted mean skin temperature was calculated. Sweating rate was measured by resistance hygrometry from six regions. When head skin temperature was increased, deep body temperature measured at the tympanic membrane and oral cavity increased more than esophageal temperature, while rectal temperature remained essentially unchanged. Sweating rate increased when head skin temperature increased and again, somewhat later, as the tympanic membrane and oral temperatures began to rise. When head skin temperature was decreased, tympanic membrane and oral temperatures decreased and sweating again followed the changes in skin temperature as well as the changes in tympanic membrane and oral temperatures. Since it has been shown that head skin temperature is particularly important in determining thermal comfort and sweating rate when compared to other body regions, it is suggested that this particular sensitivity is in part due to a thermal counter-current exchange between venous blood draining the head and arterial blood ascending to intracranial thermoreceptors. Such an exchange would correspond to similar mechanisms present in other species.
Body Temperature↗
Preemptive intrathecal ketamine injection produces a long-lasting decrease in neuropathic pain behaviors in a rat model.
BACKGROUND AND OBJECTIVES: Ketamine is an N-Methyl-D-Aspartate (NMDA) receptor antagonist, which has been found to effectively treat somatic and neuropathic pain. This study examines the effect (on neuropathic pain) of preemptive ketamine using different routes of administration (intrathecal versus intraperitoneal). METHODS: The Institutional Animal Care and Use Committee approved the study. Thirty male Sprague-Dawley rats (250-275 g) were divided into three treatment groups [intrathecal saline/intraperitoneal saline or Control (CTL), intrathecal ketamine/intraperitoneal saline (ITK), and intrathecal saline/intraperitoneal ketamine (IPK)] prior to undergoing surgery to induce neuropathic pain by tight ligation of the left L5 and L6 spinal nerves. All drugs were given 15 minutes before nerve ligation. The ITK group received intrathecal ketamine (0.5% solution, 1 mg/kg), the IPK group received intraperitoneal ketamine (0.5% solution, 1 mg/kg), saline was given in equal volume (approximately 0.05 mL). Mechanical allodynia, cold allodynia, and ongoing pain behaviors indicative of neuropathic pain were assessed on postoperative days 1, 3, 7, and 14 using validated methods. RESULTS: Compared with the CTL group, the ITK group showed a state of decreased mechanical allodynia, cold allodynia, and ongoing pain as revealed by the von Frey hair, acetone, and cold plate testing, respectively. Further, this decrease was sustained for at least 2 weeks. The IPK group showed intermediate results between the CTL and ITK. CONCLUSIONS: Neuropathic pain behaviors were significantly reduced for at least 2 weeks after intrathecal ketamine was preemptively administered to animals undergoing surgery to induce neuropathic pain. The mechanism of action is thought to be prevention of spinal cord sensitization.
Analgesics↗
A double-blind, randomized, parallel group study of omeprazole and ranitidine in Korean patients with gastric ulcer.
The efficacy of the proton pump inhibitor omeprazole, 20 mg every morning, was compared with that of the H2-receptor antagonist ranitidine, 150 mg every morning and at bedtime, in a double-blind randomized parallel group study in 250 patients with gastric or prepyloric ulcers. At both 4 and 8 weeks, significantly more patients had healed ulcers in the omeprazole group than the ranitidine group, whether the results were analysed on a per-protocol or an intention-to-treat basis. At 4 weeks, 74% of patients in the omeprazole group were healed compared with 51% in the ranitidine group (P = 0.001), and at 8 weeks the corresponding values were 99 and 82% (P = 0.001, per-protocol cohort). Omeprazole treatment and small ulcer size significantly increased the probability of healing, but smoking had no significant effect. Patients in the omeprazole group had significantly fewer occurrences of daytime epigastric pain during the first 4 weeks than the ranitidine group (P = 0.0037), as shown by their diary cards. Both treatments were well tolerated.
Adult↗