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M M Morgan

Publications and source records attributed to M M Morgan.

At least 19 recordsLinked to original sources
PubMed1992

Activity of neurons in the rostral medulla of the halothane-anesthetized rat during withdrawal from noxious heat.

The physiological and pharmacological properties of two classes of putative nociceptive modulatory neurons have been extensively characterized in the rostral ventromedial medulla (RVM) of the barbiturate-anesthetized rat. 'On-cells' show a burst of activity, and 'off-cells' a sudden pause immediately preceding the occurrence of nocifensor reflexes. In the present study, we have characterized the reflex-related activity of RVM neurons in halothane-anesthetized rats to determine whether the properties of these neurons are dependent on barbiturate anesthesia. Both on- and off-cells were identified in this preparation. Repeated noxious stimulation was associated with a high level of ongoing activity in on-cells, and a low level in off-cells. These data thus demonstrate that the previously described reflex-related changes in RVM neuron activity are not specific to barbiturate-anesthetized preparations, and that a failure to demonstrate off-cells in some studies may result from these neurons being inactive following repeated testing with noxious stimuli.

Action Potentials↗
PubMed1992

Circuitry linking opioid-sensitive nociceptive modulatory systems in periaqueductal gray and spinal cord with rostral ventromedial medulla.

The interactions among opioid-sensitive nociceptive modulatory systems, which include the midbrain periaqueductal gray, rostral ventromedial medulla and spinal cord, are likely to play a central role in the potent antinociception that results when morphine is administered systemically. The aim of the present study was to investigate the mechanisms through which local application of morphine, either in the periaqueductal gray or at the lumbar spinal cord in the rat, influences the activity of one population of putative nociceptive modulatory neurons in rostral ventromedial medulla, i.e. "on-cells". Previous studies have shown that the spontaneous and tail-flick-related firing of on-cells is invariably depressed when morphine is given systemically in doses demonstrated to inhibit the tail-flick reflex, and that a similar depression of this activity is produced when morphine is applied directly in the periaqueductal gray or intrathecal space. In the present experiments, on-cells were activated pharmacologically using iontophoretically applied glutamate to provide an indication of whether morphine-induced suppression of on-cell firing reflected a postsynaptic inhibition or a disfacilitation resulting from blockade of an excitatory input to the on-cell. Microinjection of morphine into the periaqueductal gray blocked glutamate-evoked activity of on-cells in parallel with its suppression of the tail-flick reflex, suggesting activation of an inhibitory input to these cells. No change in glutamate-evoked activity occurred in rats in which morphine did not produce antinociception. Intrathecal administration of morphine did not alter the glutamate-evoked activity of these neurons despite blocking the tail-flick reflex, suggesting that morphine acting in the spinal cord removes an excitatory input to on-cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Direct and indirect actions of morphine on medullary neurons that modulate nociception.

The rostral ventromedial medulla is part of a neural network through which systemically administered morphine produces antinociception. Two physiologically characterized classes of presumed nociceptive modulating neurons that respond differentially to systemically administered morphine have been identified in this region: the firing of "on-cells" is depressed, whereas "off-cells" become continuously active. On-cells have been proposed to permit or facilitate, and off-cells to inhibit, nociceptive transmission. Because local application of morphine in the rostral ventromedial medulla itself is sufficient to produce antinociception, it is important to determine whether systemically administered morphine exerts its effects on neurons in this region by a direct action. Thus, activity of physiologically characterized neurons was studied before, during and after ionotophoretic administration of morphine. As with systemic administration, iontophoretic application of morphine depresses the activity of on-cells, an effect that is reversed by iontophoretic as well as by systemic administration of naloxone. In contrast, no reliable changes in the firing of off-cells are produced by iontophoretic administration of morphine. Cells of a third class, "neutral cells", are not affected by systemic morphine administration, nor do they respond to iontophoretic application of the drug. The present experiments demonstrate that direct opioid responsiveness in the rostral ventromedial medulla is limited to a single physiologically characterized class of presumed nociceptive modulatory neuron, the on-cell. This implies that the antinociceptive effect exerted by systemically administered morphine involves at least two components within the rostral ventromedial medulla: a direct inhibition of on-cells, and an indirect activation of off-cells. Each of these actions is likely to have a net hypoalgesic effect.

Animals↗
PubMed1991

Stimulation of the periaqueductal gray matter of the rat produces a preferential ipsilateral antinociception.

The few studies analyzing somatotopic organization of stimulation-produced antinociception (SPA) from the periaqueductal gray matter (PAG) have reported contradictory results. In the present study, the distribution of SPA on the hindquarters was assessed by measuring the threshold for inhibition of withdrawal reflexes to noxious heat applied to the hindpaws and tail in pentobarbital-anesthetized rats. Of the 3 body regions tested, the hindpaw contralateral to the stimulating electrode required the highest level of PAG stimulation to inhibit withdrawal. Reducing the intensity of the heat stimulus applied to the hindpaws caused a concomitant reduction in SPA threshold. As before, a higher stimulation current was needed to inhibit the withdrawal reflex in the contralateral than in the ipsilateral paw. These data indicate the antinociception from PAG stimulation is not equally distributed throughout the body, and that the intensity of the noxious stimulus influences the threshold for SPA.

Animals↗
PubMed1991

Periaqueductal gray stimulation produces a spinally mediated, opioid antinociception for the inflamed hindpaw of the rat.

The objective of the present study was to characterize stimulation-produced antinociception from the periaqueductal gray matter (PAG) in rats with unilateral hindlimb inflammation induced by an intraplantar injection of Freund's complete adjuvant. Rats were chronically implanted with a bipolar stimulating electrode in the PAG. Nociception was assessed using a paw pressure test. Prior to inflammation, PAG stimulation significantly increased paw pressure threshold in both paws compared to non-stimulated controls. Following inflammation, PAG stimulation inhibited nociception in the inflamed, but not the non-inflamed paw. Systemic administration of naloxone blocked antinociception from ventral, but not dorsal PAG stimulation sites. Intrathecal, but not subcutaneous, administration of quaternary naltrexone completely blocked stimulation-produced antinociception from the PAG. The known increased levels of endogenous opioids occurring in the spinal cord ipsilateral to the site of inflammation suggest a mechanism for the selective antinociceptive effect of ventral PAG stimulation seen for the inflamed paw.

Analysis of Variance↗
PubMed1991

Patterns of CD16 and CD56 expression in persistent expansions of CD3+NKa+ lymphocytes are predictive for clonal T-cell receptor gene rearrangements. The Yorkshire Leukaemia Group.

Phenotypic characteristics, and correlations between the expression of membrane NK-associated (NKa) determinants (CD11b, CD16, CD56 and CD57) and T cell receptor (TCR) genotypic patterns, were examined in 25 patients with persistent (greater than 6 months) expansions of CD3+WT31+NKa+ (CD8+ and CD8dim+) lymphocytes. These studies showed that distinct NKa phenotypic profiles were restricted to cases with rearranged TCR configurations and that clonal CD3+NKa+ components could be predicted in most cases by assessing relationships between membrane CD16 and CD56 expression. For all normal NKa subpopulations, there was a high correlation (P less than 0.0001; n = 31) between the expression of these two membrane determinants. Markedly increased CD16 expression by CD3+NKa+ cells, in relation to CD56 (i.e. a high CD16:CD56 ratio), was found exclusively in cases with rearranged TCR (13/16 cases); 2/3 of the remaining cases showing significantly reduced CD16:CD56 ratios and high (greater than 2.0) CD3+CD56+ absolute numbers. In contrast, 7/9 of the germline TCR cases had a normal CD16:CD56 ratio and 2/9 a decreased ratio with low (less than 1.0) CD3+CD56+ absolute numbers. A high ratio of CD16:CD56 expression by CD3+NKa+ lymphocytes was therefore informative for 82% of TCR rearrangements in this series; and analysis of CD16 and CD56 expression was predictive for germline and rearranged TCR configurations in 24/25 persistent CD3+NKa+ expansions.

Adult↗
PubMed1991

The sensitivity of medical diagnostic decision-support knowledge bases in delineating appropriate terms to document in the medical record.

A pertinent, legible and complete medical record facilitates good patient care. The recording of the symptoms, signs and lab findings which are relevant to a patient's condition contributes importantly to the medical record. The consideration and documentation of other disease states known to be related to the patient's primary illness provide further enhancement. We propose that developing sets of disease-specific core elements which a physician may want to document in the medical record can have many benefits. We hypothesize that for a given disease, terms with high importance (TI) and frequency (TF) in the DX-plain, QMR and Iliad knowledge bases (KBs) are terms which are used commonly in the medical record, and may be, in fact, terms which physicians would find useful to document. A study was undertaken to validate ten such sets of disease-specific core elements. For each of ten prevalent diseases, high TI and TF terms from the three KBs mentioned were pooled to derive the set of core elements. For each disease, all patient records (range 385 to 16,972) from a computerized ambulatory medical record database were searched to document the actual use by physicians of each of these core elements. A significant percentage (range 50 to 86%) of each set of core elements was confirmed as being used by the physicians. In addition, all medical concepts from a selection of full text records were identified, and an average of 65% of the concepts were found to be core elements.(ABSTRACT TRUNCATED AT 250 WORDS)

Artificial Intelligence↗
PubMed1989

Stimulation of the periaqueductal gray matter inhibits nociception at the supraspinal as well as spinal level.

Stimulation of the periaqueductal gray matter (PAG) is known to modulate nociception at the spinal level. Several studies have suggested that nociception may also be modulated via ascending projections from the PAG. To study this hypothesis, the descending pathway was selectively disrupted immediately caudal to the PAG in 28 rats. Twenty-eight additional rats served as non-lesioned controls. All animals were chronically implanted with a stimulating electrode in the PAG, and antinociception was assessed using tests involving spinally and supraspinally mediated responses (tail-flick and hot-plate tests, respectively). Significantly fewer lesioned than non-lesioned rats showed stimulation-produced analgesia (SPA) in the tail-flick test (4 of 28 vs 14 of 28, respectively). In contrast, no significant difference in the incidence of SPA occurred between lesioned and non-lesioned rats in the hot-plate test. These findings demonstrate that nociception can be modulated at the supraspinal, as well as spinal, level.

Animals↗
PubMed1989

Characterization of stimulation-produced analgesia from the nucleus tractus solitarius in the rat.

Electrical stimulation of the commissural region of the nucleus tractus solitarius (NTS) inhibits the tail-flick reflex evoked by noxious heat. This antinociception can be measured in the awake or pentobarbital anesthetized rat at current intensities that do not induce overt behavioral side effects. Glutamate microinjections into the NTS, but not immediately surrounding the NTS, also inhibit the tail-flick reflex, demonstrating that activation of NTS cell bodies, and not fibers of passage, mediates antinociception from this region. In contrast, morphine microinjections into the NTS have no effect on the tail-flick reflex in anesthetized rats. These findings provide further evidence that the NTS is involved in the modulation of nociception.

Analgesia↗
PubMed1988

Sequence of the small double-stranded RNA genomic segment of infectious bursal disease virus and its deduced 90-kDa product.

The smaller dsRNA segment of the genome of infectious bursal disease virus (IBDV) encodes a single polypeptide of approximately 90 kDa (VP1). The consensus nucleotide sequence, derived from independent and overlapping cDNA clones, contains a single open reading frame which begins with an exact Kozak sequence and could encode a polypeptide of 878 amino acid residues. It has been suggested that VP1 could be the viral RNA-dependent RNA polymerase. A comparison of the predicted amino acid sequence of this protein with those of other DNA-dependent and ssRNA-dependent RNA polymerases has failed to reveal any homology between VP1 and the conserved regions in these enzymes. It is possible that the polypeptide encoded by the IBDV virus may represent a new class of polymerases which are involved in the replication of double-stranded RNA genomes.

Amino Acid Sequence↗
PubMed1987

GABAergic modulation of the analgesic effects of morphine microinjected in the ventral periaqueductal gray matter of the rat.

The possibility that GABAergic neurons in the ventral periaqueductal gray matter modulate the analgesic effects of morphine microinjected into this brain area was investigated in the rat. Microinjection of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin 3-ol (THIP) (0.4 microgram in 0.2 microliter), a GABA agonist, in the ventral periaqueductal gray matter significantly reversed the increase of tail-flick latency induced by a prior injection of morphine sulfate (4 micrograms in 0.2 microliter) at the same site. Conversely, microinjection in the same region of picrotoxin (10 ng in 0.2 microliter), a GABA antagonist, significantly potentiated the analgesic effect of the same dose of morphine. These results suggest the existence of GABAergic neurons that tonically inhibit periaqueductal gray output neurons involved in centrifugal pain inhibition. The analgesic effects of opiates may, at least in part, result from disinhibition of these GABAergic neurons.

Animals↗
PubMed1987

Site specificity in the development of tolerance to stimulation-produced analgesia from the periaqueductal gray matter of the rat.

Pentobarbital-anesthetized rats were subjected to 21 min of continuous electrical stimulation of the caudal periaqueductal gray matter (PAG) at the current threshold for analgesia. Stimulation at ventral PAG sites supported analgesia for only 1 or 2 min in most animals. Stimulation at more dorsal PAG sites supported analgesia for the entire 21 min of stimulation. This demonstration of acute tolerance with continuous ventral, but not more dorsal, PAG stimulation corresponds well with previous evidence suggesting opioid mediation of analgesia from this brain region.

Analgesia↗
PubMed1987

Diazepam dissociates the analgesic and aversive effects of periaqueductal gray stimulation in the rat.

Electrical stimulation of the periaqueductal gray matter (PAG) of the rat can produce both analgesia and aversive reactions. To determine if these two effects can be dissociated, diazepam, a benzodiazepine, was administered to rats chronically implanted with electrodes in the PAG. The threshold for stimulation-produced analgesia or aversion, whichever was lowest, was determined before and after drug administration. Diazepam (1 mg/kg) attenuated stimulation-produced aversive reactions at 12 of 20 stimulation sites, allowing analgesia to be measured at the same threshold. Diazepam did not alter baseline pain sensitivity or thresholds for stimulation-produced analgesia. These results indicate that aversive reactions and analgesia from PAG stimulation can be pharmacologically dissociated.

Analgesia↗
PubMed1987

Characterization of the analgesic effects of the benzodiazepine antagonist, Ro 15-1788.

Three experiments were carried out in rats to evaluate the analgesic effects of the benzodiazepine antagonist, Ro 15-1788. Expt. 1 demonstrated a diazepam reversible analgesic effect of Ro 15-1788 using the tail-flick test. Expt. 2 analyzed the effects of Ro 15-1788 in the hot-plate test at various doses. Low doses of Ro 15-1788 proved analgesia 20 min after drug injection, whereas high doses had no analgesic effect on the 20 min test, but were effective on the 50 min test. Expt. 3 demonstrated that the opiate antagonist, naloxone, had no effect on analgesia produced by Ro 15-1788 in the hot-plate test. The analgesic effects of Ro 15-1788 may be attributable to its reported anxiogenic properties.

Analgesics↗
PubMed1987

Barbiturate-induced inhibition of a spinal nociceptive reflex: role of GABA mechanisms and descending modulation.

The present study investigated the effect of systemically administered pentobarbital on the tail-flick (TF) reflex in rats, the neurochemical mechanism of action and the role of descending influences. Pentobarbital produced a clear inhibition of the TF response. Systemic administration of naloxone did not significantly alter this effect, thus it appears to be independent of endogenous opioid systems. Complete spinal transection resulted in a marked potentiation of pentobarbital-induced TF inhibition, demonstrating a spinal locus of action. Moreover, this observation suggests the existence of a tonic descending excitatory influence, opposing the pentobarbital-produced depression of nociceptive transmission in the intact animal. Intrathecal administration of pentobarbital caused a much more pronounced TF inhibition in transected than in intact animals, lending further support to this hypothesis. To identify the neurochemical mechanisms involved in pentobarbital-produced antinociception, the gamma-aminobutyric acid (GABA) antagonists bicuculline and picrotoxinin were administered intrathecally in spinalized animals. Both substances caused an attenuation of the pentobarbital effect, demonstrating the involvement of GABAergic transmission. The proposed descending excitatory system may act either presynaptically and cause a decreased release of GABA into the synapse or postsynaptically via endogenous GABA antagonistic neurotransmitters, which may change the conformation of the GABA-barbiturate receptor complex.

Analgesics↗
PubMed1987

The mitochondrial genotype can influence nuclear gene expression in yeast.

Isochromosomal, respiratory-deficient yeast strains, such as a mit-, a hypersuppressive petite, and a petite lacking mitochondrial DNA, are phenotypically identical in spite of differences in their mitochondrial genomes. Subtractive hybridizations of complementary DNA's to polyadenylated RNA isolated from derepressed cultures of these strains reveal the presence of nuclear-encoded transcripts whose abundance varies not only between them and their respiratory-competent parent, but among the respiratory-deficient strains themselves. Transcripts of some nuclear-encoded mitochondrial proteins, like cytochrome c and the alpha and beta subunits of the mitochondrial adenosine triphosphatase, whose abundance is affected by glucose or heme, do not vary. In the absence of major metabolic variables, yeast cells seem to respond to the quality and quantity of mitochondrial DNA and modulate the levels of nuclear-encoded RNA's, perhaps as a means of intergenomic regulation.

Base Sequence↗
PubMed1987

Different effects of chronic nicotine treatment regimens on body weight and tolerance in the rat.

The effect of different chronic nicotine administration regimens on body weight and the development of tolerance was examined in female rats. Groups of animals were either treated with nicotine via a subcutaneous continuous release pellet or via two injections each day of either a high (5.6 mg/kg) or low (0.8 mg/kg) dose. Both the Pellet and Low injection groups showed a progressive weight loss during nicotine treatment followed by a weight gain upon cessation of treatment, but the time course and size of these weight changes were quite distinct. In contrast, the High injection group gained weight during the 17 days of nicotine treatment. Tolerance, as measured by locomotor activity following an acute injection of nicotine 1 week after cessation of chronic nicotine treatment, was evident only in the Low injection group. This study demonstrates that the regimen in which nicotine is administered is an important factor in determining the behavioral effects produced by chronic nicotine treatment.

Animals↗