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K L Casey

Publications and source records attributed to K L Casey.

18 recordsLinked to original sources
PubMed1992

Neurophysiological, pharmacological and behavioral evidence for medial thalamic mediation of cocaine-induced dopaminergic analgesia.

These studies examined the effects of cocaine on thalamic neurons that respond maximally either to noxious or to innocuous somatic stimulation. Cocaine attenuated high intensity electrically-evoked nociceptive responses of all 25 units studied in the parafascicular and central lateral nuclei of the medial thalamus. A dose of 1 mg/kg intravenously (i.v.) suppressed medial thalamic unit discharge evoked by both noxious somatic stimulation (49.4 +/- 8.7% of control response) and spinal cord stimulation (76.2 +/- 6.6% of control response). The effect of cocaine on unit responses to noxious somatic stimulation was dose-related in the range of 0.3-3.5 mg/kg i.v. and was attenuated by eticlopride, a D-2 selective dopamine receptor antagonist. Morphine also suppressed noxious somatic evoked responses of medial thalamic units in a dose-dependent manner. Units in the lateral (ventrobasal) thalamus (n = 4) that responded only to innocuous stimuli were not affected by cocaine at doses up to 3.5 mg/kg i.v. Ibotenic acid lesions in the parafascicular nucleus of the medial thalamus attenuated the analgesic effect of cocaine in the formalin test. These results suggest that both cocaine and the parafascicular nucleus interact with dopaminergic mechanisms that attenuate nociceptive spinal projections to the medial thalamus.

Analgesics↗
PubMed1992

State-related modulation of thalamic somatosensory responses in the awake monkey.

1. These experiments were performed to assess the nature and extent of the modulation of somatosensory transmission through the thalamus of the awake primate brain. We investigated physiologically induced modulation occurring during changes in state of arousal within the waking state. Changes in thalamic responsiveness during the sleep-waking cycle were not studied. 2. We recorded from single units in several nuclei within the ventral posterior region of the thalamus (VP) of awake squirrel monkeys (Saimiri sciureus). Recording sites included the ventral posterior lateral, ventral posterior medial, ventral posterior inferior, ventral lateral, and thalamic reticular nuclei. Four hundred twenty-seven thalamic units were tested for responsiveness to innocuous and noxious somatic stimulation of cutaneous (hair and skin) and deep (muscle and tendon) structures and to innocuous electrical stimulation of the spinal lemniscus (SL). Noxious stimuli were just sufficient to evoke withdrawal and did not cause tissue damage. 3. All neurons were spontaneously active in the absence of intentional stimulation. Only 260 (60.9%) of the neurons recorded in VP responded to somatic or SL stimulation. Based on their responsiveness to somatic stimuli, we classified neurons as cutaneous (67.7% or 176/260) if responsive to hair and/or skin stimulation or as deep (18.8% or 49/260) if responsive only to manipulation of joints or palpation of muscles or tendons. Thirty-five other cells (13.5%) responded best to brisk innocuous taps applied to the somatic receptive field and were placed in a separate group. Cutaneous units were subclassified as low-threshold (LT, 86.9% or 153/176) if responding maximally to innocuous stimuli only or as wide dynamic range (WDR, 13.1% or 23/176) if responding preferentially to noxious stimuli. No neurons responded exclusively to noxious stimuli. Single-pulse SL stimulation evoked discharges at an average latency of 3.3 +/- 4.8 (SD) ms in 51/132 (38.6%) LT neurons tested and similarly affected 7 of 12 WDR cells tested at an average latency of 1.54 +/- 0.39 ms. 4. We tested 88 neurons for changes in activity as the monkey's state of arousal shifted between quiet waking (QW), waking movement (WM), and drowsy (D) states as defined by behavioral and electroencephalographic criteria. The responses of 42% of the 88 somatically activated cells tested (n = 37) showed arousal-related response modulation (ARM). ARM produced a mean change in evoked activity of 40.1% (+/- 23.5 SD) relative to that cell's maximal response and the specific state of arousal during which the maximal response occurred. Neurons classified as WDR were equally likely to exhibit ARM as LT neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

The effect of systemic cocaine on the responses to noxious stimuli and spontaneous activity of medial bulboreticular projection neurons.

The effect of antinociceptive doses of cocaine (25 mg/kg, i.p.) on unit responses to noxious somatic stimuli and spontaneous activity of antidromically identified projection neurons in the medial medullary reticular formation (MRF) was studied in the rat. Thirty-three antidromically activated neurons were recorded from the medullary raphe, gigantocellular, or paragigantocellular nuclei in an acute anaesthetized preparation; 25 cells projected to the spinal cord and 8 neurons had rostral projections through the medial forebrain bundle (n = 4) or the medial thalamus (n = 4). After cocaine administration, 24 (73%) of these cells showed immediate (less than 5 min) and prolonged (45-70 min) increases in their level of spontaneous activity. Associated with this increased interstimulus activity, 21 of 29 (72%) neurons responsive to noxious somatic stimulation reduced their responsiveness, relative to prestimulus activity, after cocaine administration. In 5 animals tested, the cocaine-induced changes in spontaneous activity and changes in evoked responsiveness were unaffected by naloxone (1 mg/kg, i.p.) but partially reversed within 5 min of the administration of chlorpromazine (3 mg/kg, i.p.). There were no obvious differences in neuronal response characteristics or the effect of cocaine that correlated with anatomical location or direction of axonal projection. Similar results were obtained while recording from 14 somatically responsive units in chronic, unrestrained, lightly anesthetized or awake rats. These findings provide direct evidence that cocaine, in doses that are antinociceptive for the rat, affects both unit responses to noxious stimuli and the spontaneous activity of caudally and rostrally projecting bulboreticular neurons over a time course that parallels the behavioral antinociception. The observation that unit responses to somatic stimuli were reduced while spontaneous activity was unchanged or increased in most cells suggests that cocaine antinociception may be due to the activation of sensory inhibitory mechanisms mediated by the MRF.

Animals↗
PubMed1990

The effect of systemic cocaine on spontaneous and nociceptively evoked activity of neurons in the medial and lateral thalamus.

In rats, analgesic doses of cocaine (25 mg/kg, i.p.) suppressed the responses of 20 of 22 medial and lateral thalamic neurons to reticular formation and somatic noxious stimuli. The responses of 7 of 8 lateral thalamic neurons to innocuous somatic stimuli were unaffected or enhanced. The suppression of thalamic responses to noxious stimuli may be part of the mechanism underlying cocaine analgesia.

Action Potentials↗
PubMed1989

Effect of medial bulboreticular and raphe nuclear lesions on the excitation and modulation of supraspinal nocifensive behaviors in the cat.

Six cats were trained to eat while partially restrained and while thermal pulse stimuli (43-60 degrees C, 5 s duration) were delivered to the upper hindlimbs. Food and stimulus delivery were under programmed electronic control. The probability and latency of 3 natural, unlearned nocifensive behaviors were electronically registered: interruption of eating or of exploring for food, hindlimb movement and vocalization. Preoperatively, all cats showed significant increases in the probability of two or more behaviors as stimulus temperature increased. Each cat also showed a significant food-induced suppression of one or more of these behaviors. Thermocoagulation lesions limited to the giganto- and magnocellular fields of the medial medullary reticular formation (4 cats) produced a decrease in nocifensive responsiveness. Larger lesions within the same area but with extension into the postpyramidal raphe nuclei, resulted in increased nocifensive responsiveness (2 cats). No lesion affected response latency or the food-induced modulation of nocifensive behavior. The results support the hypothesis that supraspinally organized nocifensive responses are: (1) tonically facilitated by neural activity originating in or passing through the medial bulboreticular formation; (2) tonically suppressed by midline raphe spinal neurons; and (3) phasically modulated by suprabulbar neural mechanisms that are related to changes in behavioral state.

Animals↗
PubMed1989

Cocaine: evidence for supraspinal, dopamine-mediated, non-opiate analgesia.

Cocaine (25 mg/kg i.p.) produces analgesia in the rat within 5 min and for a duration of 90 min as determined by the formalin test or for 30 min as determined by the hot plate test. Cocaine analgesia is unaffected by doses of naloxone that are sufficient to attenuate morphine analgesia in both tests. Chlorpromazine (3 mg/kg i.p.), SCH 23390 (100 micrograms/kg i.p.; a D1 dopamine receptor antagonist), and eticlopride (75 micrograms/kg i.p.; a D2 dopamine receptor antagonist) each attenuate cocaine analgesia in both tests at doses that alone do not affect performance in either test. Measurements of blood pressure and heart rate indicate that cocaine analgesia is not due to the activation of baroreceptor reflex afferents. We conclude that cocaine is a supraspinally acting, dopamine-mediated, non-opiate analgesic in the rat.

Analgesia↗
PubMed1988

Supraspinal nocifensive responses of cats: spinal cord pathways, monoamines, and modulation.

These experiments were conducted to determine (1) whether dorsal and ventral ascending spinal pathways can each mediate unlearned supraspinal nocifensive responses of cats to noxious thermal stimuli and (2) whether interrupting the spinal projection of supraspinal monoaminergic neurons alters the excitability and natural modulation of these responses. In partially restrained cats, thermal pulses (greater than or equal to 47 degrees C) delivered to the hindlimbs of intact cats or rostral to lesions of the thoracic spinal cord elicited abrupt body movements and interruption of eating (or of exploring for) liquified food. These electronically monitored responses automatically terminated the stimulus. Natural modulation of responsiveness was produced by delivering food and thermal stimuli simultaneously; this reduced response probability by an average of 41%. Complete transection of the thoracic spinal cord eliminated both thermally elicited responses and orienting responses to noxious and tactile mechanical stimulation of the hindlimbs. Ventral bilateral thoracic spinal cord lesions that spared only the dorsal funiculus and portions of the dorsolateral funiculus (three cats) significantly reduced orienting responses to all mechanical hindlimb stimuli and reduced, but did not eliminate, movement and interrupt responses to noxious thermal hindlimb stimuli. Response latency was unaffected. Food-induced response suppression persisted although lumbar spinal cord concentrations of serotonin (5HT) and norepinephrine (NE) were markedly reduced. A bilateral lesion of the dorsal funiculi and dorsal portions of the dorsolateral funiculi (one cat) also reduced nocifensive responsiveness, but only the NE concentration in lumbar spinal cord was reduced significantly relative to a matched cervical sample. In contrast, deep bilateral lesions of the dorsolateral funiculi (two cats) produced an increase in the probability of movement and interrupt responses without affecting either response latency or food-induced response suppression. Lumbar spinal cord concentrations of NE and, in one cat, 5HT were reduced. We conclude that (1) the dorsal and ventral spinal funiculi are each sufficient to initiate and necessary to maintain normal supraspinally organized nocifensive behavior in the cat; (2) descending monoaminergic pathways are not necessary for the phasic modulation of these responses; and (3) the tonic excitability, but not the phasic modulation, of these responses is determined in part by fibers in the dorsolateral funiculus.

Animals↗
PubMed1988

The effect of systemic cocaine on spinal nociceptive reflex activity in the rat.

In the anesthetized rat, cocaine (25 mg/kg i.p.), enhanced the frequency potentiation of nociceptively evoked polysynaptic discharges but did not affect the polysynaptic reflex discharge to single nociceptive stimuli or the habituation of this reflex to repetitive pinch stimuli. The non-nociceptive, short-latency reflex discharge was suppressed for 10-15 min after cocaine administration. The neurogenic extravasation response to antidromic cutaneous C-fiber stimulation was unaffected by cocaine. These findings suggest that systemic cocaine, in doses analgesic for the rat, does not suppress spinal nociceptive reflexes.

Action Potentials↗
PubMed1988

Physiological identification of afferent fibers and postsynaptic sensory neurons in the spinal cord of the intact, awake cat.

A method was developed to record from spinal cord cells in the awake, intact, partially restrained cat. Units were classified as afferent fibers or postsynaptic cells based on their ability to follow 100-Hz peripheral stimulation, the duration and configuration of the action potential waveform, and the number of spikes evoked by a single electrical pulse. These criteria are supported by independent observations of the location of the recording site, size of the receptive field, and adequate stimulus. Of 84 cutaneously activated units, 29 were classified as afferent fibers, 28 as postsynaptic cells, and 27 were not classified. No cutaneously activated unit was spontaneously active. In contrast, all 28 units (7 postsynaptic and 21 not classified) responding to joint position or movement were spontaneously active (5 to 40 Hz). No unit responded to both cutaneous and proprioceptive inputs. Evidence for convergence of cutaneous input from different types of receptors was limited to five postsynaptic neurons that responded to hair movement and to stimuli applied to the skin; two of these cells responded differentially to noxious pinch. Two of 24 postsynaptic cutaneous units ceased responding to electrical cutaneous stimuli when the cat was eating. The responses of 29 primary afferent fibers were not altered by the behavior of the cat. These results suggest that, in the awake cat (i) criteria based on neuronal responsiveness and action potential waveform can be used to distinguish adequately between afferent fibers and postsynaptic cells; and (ii) there is a tonic inhibitory control, greater than in the anesthetized or spinally transected cat, that varies with behavioral state and is directed primarily at spinal neurons receiving cutaneous input.

Afferent Pathways↗
PubMed1988

Modulation of the spontaneous and evoked discharges of ventral posterior thalamic neurons during shifts in arousal.

The responses of 154 ventral posterior thalamic neurons to a variety of somatic stimuli and to electrical stimulation of the midbrain spinal lemniscus were recorded in the awake squirrel monkey during varying states of arousal. Many VP (42/93) neurons showed changes in somatosensory responsiveness which correlated with shifts in arousal. Arousal related modulation (ARM) of somatic responses were not selective for any specific stimulus modality. Most cells (N = 36) responded maximally during quiet waking with responses significantly reduced during drowsiness or periods of waking movement. Other neurons (N = 5) responded maximally during drowsiness, and gave decreased responses as the level of arousal increased. Similar changes were seen for neurons driven by spinal lemniscal (SL) stimulation. All changes in evoked responses were independent of prestimulus background discharge frequency. At least one site of ARM takes place at the level of the VP thalamus.

Action Potentials↗
PubMed1987

Differential effects of chronic partial myelotomies on monoamine levels in cat spinal cord.

The concentrations of 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA) were measured in samples of lumbar and cervical spinal cords from 6 cats with chronic (over 2 months) lesions of the thoracic spinal cord and from 7 unoperated cats. Lesions confined to the dorsal thoracic spinal cord significantly lowered lumbar concentrations of NE, but not 5-HT, compared with control lumbar or matched paired cervical samples. Both NE and 5-HT were significantly reduced by dorsal or ventral lesions that involved tissue ventral to the central canal. Only the largest lesion could be shown to reduce lumbar DA concentration.

Animals↗
PubMed1986

A microprocessor device for the real-time detection of synchronized alpha and spindle activity in the EEG.

A microprocessor based device is described which permits the real-time detection of synchronized EEG activity within the frequency range of the alpha rhythm or sleep spindles. This device offers a reliable, inexpensive method for EEG analysis according to flexible, user selectable parameters. It can be used either on-line or off-line and provides information as to the occurrence and duration of alpha-spindle EEG activity.

Alpha Rhythm↗
PubMed1986

Corticofugal influences of S1 cortex on ventrobasal thalamic neurons in the awake rat.

Corticofugal influences on the responses of 39 ventrobasal (VB) thalamic neurons to repetitive stimuli were studied in awake rats by focally suppressing the evoked and spontaneous electrocortical activity of the primary (S1) somatosensory cortex with magnesium or lidocaine plus magnesium. Suppression of the S1 cortex reduced the number of spikes discharged by 19 (66%) of 29 VB units in response to each of 25 electrical stimuli delivered to the medial lemniscus; 9 units were unaffected and 1 showed an increased response to 1-10 Hz stimuli. The responses of 6 (38%) of 16 VB units to electrical somatic stimuli were also reduced following S1 cortical suppression; 9 units were unaffected and 1 showed an increased response to 20-40 Hz stimuli. A comparison of the reduced responsiveness of 5 units studied during medial lemniscal and somatic stimulation did not reveal any additional response attenuation attributable to subthalamic corticofugal influences. We conclude that, in the awake rat, somatosensory transmission to VB thalamic neurons is primarily facilitated by S1 corticothalamic neurons.

Action Potentials↗
PubMed1978

Pain.

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Animals↗
PubMed1977

Somatosensory function and cortical unit activity in cats with only dorsal column fibers.

Cats received lesions that transected the entire thoracic cord except for partial sparing of the dorsal columns. The cats were required to discriminate the side on which they were touched, the size of simultaneously presented discs, or the direction their fur was stroked to obtain food reward. All cats found by anatomical and/or electrophysiological criteria to have any functional continuity in the dorsal columns were able to master the first of these tasks; some responded above chance on the second. Performance was at chance on blank trials, and cats with complete cord transection failed to discriminate. Lesioned cats did not orient or otherwise react to any nonrewarded stimulus below the level of the lesion. A total of 532 units were recorded under light barbiturate anesthesia from the hind paw projection near the tip of the ansate sulcus in these and other similarly prepared cats. Three-fourths of the units found before and acutely after the cord lesions were made were driven by hind limb stimulation. Only 27% of the units recorded 10 or more days afterwards could be driven. Of these driven units, 15 (38%) responded to foreleg stimulation, 13 exclusively so. No such units were found in intact or acutely lesioned cats.

Animals↗
PubMedDate not supplied

Problems in the differential diagnosis of chronic pain.

Differential diagnosis is the systematic consideration of the possible cause of signs and symptoms. It requires establishing an anatomic diagnosis, in which the site of pathology is identified, and then an etiiologic diagnosis of the causal pathologic agent. The differential diagnosis is based on a knowledge of the pathophysiology of 1) the presenting signs and symptoms, and 2) the natural history of various diseases and their causative agents. Consequently, the accuracy and reliability of the differential diagnosis is limited by a lack of knowledge about the pathophysiology of various diseases that produce chronic pain. Most painful conditions affecting ectodermally derived tissues are relatively easily localized; the major problems are in the diagnosis of central nervous system pain syndromes and in our knowledge about the pathophysiology of painful neurologic disorders. The anatomic diagnosis of painful diseases of mesodermal and endodermal tissues may be difficult because of the phenomena of referred pain and tenderness. The etiologic diagnosis is made difficult by our lack of knowledge about how various pathologic processes activate nociceptors in these tissues. Finally, the differential diagnosis of chronic pain requires information about the psychological characteristics of the patient and how emotional and higher cognitive functions influence the perception of pain.

Chronic Disease↗