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K L Casey

Publications and source records attributed to K L Casey.

7 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↗
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↗