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M M Morgan

Publications and source records attributed to M M Morgan.

At least 37 records · Page 2Linked to original sources
PubMed1998

Direct comparison of heat-evoked activity of nociceptive neurons in the dorsal horn with the hindpaw withdrawal reflex in the rat.

Although the sensory coding of nociceptive neurons in the dorsal horn has been studied extensively, surprisingly little is known about how these neurons contribute to nociceptive reflexes. The objective of the present study was to examine the characteristics of dorsal horn neurons capable of initiating hindpaw withdrawal. To this end, neural and reflex activity were measured simultaneously in response to noxious radiant heat applied to the hindpaw in lightly anesthetized rats. Subsets of both multireceptive (MR; 52/95) and nociceptive-specific (NS; 19/46) neurons showed a consistent burst of activity that preceded the reflex. However, when compared with NS neurons, MR neurons as a group were: more likely to be active before the reflex (55 vs. 41%); more active before the reflex (31 vs. 23 Hz); and active earlier (2.8 vs. 2.3 s before the reflex). Subsets of MR neurons were active before the reflex regardless of receptive field size or location in the dorsal horn. In contrast, NS neurons with small receptive fields or those located outside of superficial laminae were rarely active before the reflex and thus unlikely to be part of the reflex circuit. These results suggest that current classification schemes, in particular MR and NS categories, cannot be used as the sole criterion to predict involvement in nociceptive reflexes. However, simultaneous measurement of neural and reflex activity provides an opportunity to determine the characteristics of nociceptive neurons involved in withdrawal reflexes.

Animals↗
PubMed1998

Long-term changes in compliance with clinical guidelines through computer-based reminders.

We evaluate the effectiveness of computer-based reminders in improving compliance with preventive medicine screening guidelines and examine the long-term impact of these reminders. Physicians in an ambulatory care practice were given a summary health maintenance report of preventive screening items at each scheduled patient visit. The electronic medical record (COSTAR) in use in this practice was programmed to integrate 13 clinical guidelines into the routine flow of care. Mean performance of 10 out of 13 health maintenance measures improved in the year following introduction of the integrated guideline report (p less than .001 by chi-square test for 8 items, p less than .01 for 2 items). Five years after the report was introduced, improvement in mean performance persisted for 7 measures (p less than .001 by chi-square test), compliance improved for one additional measure (p less than .001), and improvement disappeared for three measures that had shown improvement in the first year of the intervention.

Evaluation Studies as Topic↗
PubMed1997

Antinociception mediated by the periaqueductal gray is attenuated by orphanin FQ.

Orphanin FQ or nociceptin (OFQ/N(1-17)) is a recently discovered peptide which, upon intracerebroventricular administration, reverses opioid-mediated analgesias. OFQ/N(1-17) terminals are located in the periaqueductal gray (PAG), a structure known to be involved in pain modulation, suggesting that the functional anti-opioid effects of OFQ/N(1-17) are mediated by PAG neurons. To test this, subsequent microinjections of morphine or kainic acid and OFQ/N(1-17) were made into the PAG of awake rats. Administration of OFQ/N(1-17) attenuated the tail flick inhibition produced by both morphine and kainic acid microinjection. OFQ/N(1-17) attenuation of antinociception produced by a neuroexcitant indicates that OFQ/N(1-17) reverses opioid antinociception by inhibiting PAG output neurons.

Animals↗
PubMed1996

Multiple signaling pathways establish both the individuation and the polarity of the oocyte follicle in Drosophila.

The development of the Drosophila oocyte depends upon a sequential series of interactions between the germline cells and the somatically derived follicle cells to produce individual follicles with appropriate polarities. In the germarium the control of germline cell division depends upon a proper interaction with somatic cells adjacent to the germline stem cells. Both gurken and brainiac are required in the germline, and the Egfr, daughterless, Notch, and Delta genes are required in the somatic cells to produce individual egg chambers with a continuous follicular epithelium. After a follicle forms, components in these same signaling pathways, plus additional genes, are then required for the establishment of the anterior-posterior polarity, followed by the dorsal-ventral polarity of the developing follicle. Initially, gurken mRNA is localized to the posterior edge of the oocyte, where it signals the posterior polar follicle cells to differentiate as posterior. The anterior-posterior assymmetry of the oocyte is then established by a reorganization of the microtubule network, which require a Notch-Delta-dependent signal sent from the posterior polar follicle cells to the oocyte and the activity of protein kinase A in the germ line. This reorganization leads to the localization of the maternal anterior-posterior determinants bicoid and oskar to opposite poles of the oocyte and the repositioning of the oocyte nucleus to the anterior-dorsal surface of the oocyte, gurken mRNA and protein are now concentrated between the oocyte nucleus and the adjacent anterior-dorsal follicle cells, where, in combination with Rhomboid, it locally activates the EGF receptor and its downstream cascade to direct the adjoining cells to adopt a dorsal fate. This process is thought to restrict the action of three follicle cell gene functions, encoded by windbeutel, nudal, and, pipe, to the ventral follicle cells, where they lead to the localized activation of a serine protease cascade required to produce the active Spätzle ligand to activate the Toll receptor. Finally, the termini of the embryo are dependent upon the activation of the Torso receptor, and this requires the localized expression of torso-like in a subset of follicle cells at the anterior and posterior poles of the follicle, which leads to the activation of Trunk, the putative ligand for Torso. In summary, the normal development of the oocyte requires a continuous sequence of germline-follicle cell interactions to provide the polarities responsible for normal development.

Animals↗
PubMed1996

Behavioral analysis of diffuse noxious inhibitory controls (DNIC): antinociception and escape reactions.

'Diffuse noxious inhibitory controls' or DNIC is the inhibition of multireceptive neurons in the dorsal horn of the spinal cord that results when a noxious stimulus is applied to a region of the body remote from the neuron's excitatory receptive field. Although this phenomenon is well-documented, the behavioral consequences of DNIC are not clear. The present study was undertaken to determine how nocifensor withdrawal reflexes evoked by a noxious stimulus are altered by application of a second noxious stimulus to a distant part of the body. The tail flick or hindpaw withdrawal reflex of lightly anesthetized (0.6-1.0% halothane) rats was measured before, during and after another appendage was placed in water ranging in temperature from 45 to 54 degrees C. When the forepaw or hindpaw was placed in water exceeding 49 degrees C the tail flick reflex to acute noxious radiant heat was inhibited. In contrast, noxious conditioning stimuli, regardless of temperature or location, had no effect on the latency for hindpaw withdrawal evoked by an acute noxious stimulus, but did produce a change in reflex topography from flexion to extension. These results, along with previous research on DNIC, suggest that intense noxious stimuli: (1) inhibit the tail flick reflex via inhibition of multireceptive neurons in the dorsal horn; (2) disinhibit hindpaw extensor motoneurons by inhibiting the activity of multireceptive neurons involved in hindlimb flexion; and (3) reduce pain sensation by inhibiting multireceptive neurons projecting to the brain (see Model in Discussion).

Animals↗
PubMed1994

Identification of nocifensor reflex-related neurons in the rostroventromedial medulla of decerebrated rats.

Extracellular single unit recordings were made from neurons in the rostroventromedial medulla of decerebrated rats. The previously described 'on-cell' and 'off-cell' classes were found in this preparation, and this classification, which is based on tail flick-related changes in activity, was not altered by the introduction or removal of halothane anesthesia. It is therefore evident that the identifying physiological properties of on- and off-cells are not dependent on the presence of anesthesia in decerebrate rats, or on brain structures rostral to the inferior colliculi.

Anesthesia↗
PubMed1994

Diffuse noxious inhibitory controls reduce the expression of noxious stimulus-evoked Fos-like immunoreactivity in the superficial and deep laminae of the rat spinal cord.

Behavioral and electrophysiological studies have shown that a noxious stimulus applied to one part of the body can reduce the response to a subsequent noxious stimulus elsewhere on the body. This phenomenon is referred to as diffuse noxious inhibitory controls (DNIC). In the present study we used immunocytochemical labeling for the Fos protein product of the c-fos proto-oncogene to determine the location of lumbar spinal nociresponsive neurons that are inhibited by a spatially remote noxious stimulus. Repetitive hindpaw pinch evoked pronounced Fos-like immunoreactivity in the superficial and deep laminae of the lumbar spinal cord. Placing the tail in 50 degrees C water before each hindpaw pinch significantly reduced Fos-like immunoreactivity in these regions. These data demonstrate that nociresponsive neurons in both the superficial and deep laminae of the spinal cord are sensitive to inhibition by a spatially remote noxious conditioning stimulus.

Animals↗
PubMed1994

Disinhibition of off-cells and antinociception produced by an opioid action within the rostral ventromedial medulla.

Activation of neurons in the rostral ventral medulla, by electrical stimulation or microinjection of glutamate, produces antinociception. Microinjection of opioid compounds in this region also has an antinociceptive effect, indicating that opioids activate a medullary output neuron that exerts a net inhibitory effect on nociception. When given systemically in doses sufficient to produce antinociception, morphine produces distinct, opposing responses in two physiologically identifiable classes of rostral medullary neurons. "Off-cells" are activated, and have been proposed to inhibit nociceptive transmission. "On-cells" are invariably depressed, and may have a pro-nociceptive role. Although on-cell firing is also depressed by iontophoretically applied morphine, off-cells do not respond to morphine applied in this manner. The present study used local infusion of the mu-selective opioid peptide Tyr-D-Ala-Gly-MePhe-Gly-ol-enkephalin (DAMGO) within the rostral medulla to determine whether off-cells are activated by an opioid action within this region that is sufficient to produce a behaviorally measurable antinociception. Activity of on- and off-cells was recorded before and after local infusion of DAMGO noxious heat-evoked tail flick reflex was inhibited in 17 of 28 cases. On-cell firing was profoundly depressed, and this occurred irrespective of the antinociceptive effectiveness of the injection. Off-cells were activated following DAMGO microinjections, but only in experiments in which the tail flick reflex was inhibited. Both reflex inhibition and neuronal effects were reversed following systemic administration of naloxone. These observations thus confirm the role of the on-cell as the focus of direct opioid action within the rostral medulla, and strongly support the proposal that disinhibition of off-cells is central to the antinociception actions of opioids within this region.

Amino Acid Sequence↗
PubMed1994

Inhibition and facilitation of different nocifensor reflexes by spatially remote noxious stimuli.

1. Noxious stimuli have been shown to produce a diffuse inhibition of nociresponsive neurons in the spinal and trigeminal dorsal horns. The present study sought to extend these electrophysiological studies of diffuse noxious inhibitory controls (DNIC) by determining the effect of a spatially remote noxious stimulus on behavioral measures of nociception. Changes in latency for hindpaw withdrawal and tail flick reflexes were measured in lightly halothane-anesthetized or awake, spinally transected rats before, during, and after application of a spatially remote noxious stimulus. 2. Surprisingly, in no case did application of a spatially remote noxious stimulus inhibit the hindpaw withdrawal reflex. The latency for this reflex was either reduced or did not change when the tail or contralateral hindpaw was placed in hot water (50 degrees C) or when a noxious pinch was applied to the ear. In contrast, the latency for the tail flick reflex was consistently increased when the hindpaw was placed in hot water. Both the hindpaw reflex facilitation and the tail flick reflex inhibition produced by a noxious conditioning stimulus were attenuated in spinally transected rats indicating supraspinal modulation of both reflexes. 3. In addition, and consistent with the work of others, placing the tail in hot water reduced the evoked activity of convergent neurons in both the trigeminal and lumbar spinal dorsal horns. Thus inhibition of the activity of nociresponsive neurons in the dorsal horn is consistent with inhibition of the tail flick reflex, but not with facilitation of the hindpaw withdrawal reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1994

Pronounced changes in the activity of nociceptive modulatory neurons in the rostral ventromedial medulla in response to prolonged thermal noxious stimuli.

1. Brain regions that inhibit nociception can be activated by various environmental stimuli, including prolonged noxious stimuli. The present study tested the effect of such a prolonged noxious stimulus on the activity of nociceptive modulatory neurons in the rostral ventromedial medulla (RVM). These neurons, called ON- and OFF-cells because of their respective burst and pause in activity associated with nocifensor reflexes, have been shown to facilitate and inhibit nociception, respectively. 2. Single-unit activity of ON- and OFF-cells was assessed in lightly halothane- or barbiturate-anesthetized rats exposed to prolonged noxious heat (50 degrees C water). This prolonged noxious stimulus caused an increase in ON-cell and a decrease in OFF-cell activity regardless of anesthetic (halothane or barbiturate) or stimulus location (hindpaw or tail). 3. Surprisingly, and despite the consistent changes in RVM cell activity, the prolonged noxious stimulus caused different effects depending on the reflex used to assess nociception. The hindpaw withdrawal reflex was facilitated when the tail was immersed in hot water, whereas the tail flick reflex was inhibited when the hindpaw was immersed in hot water (see preceding manuscript). Lidocaine inactivation of the RVM shortened the latency for both reflexes but had no effect on tail flick inhibition produced by the noxious conditioning stimulus. In contrast, lidocaine inactivation of the RVM completely reversed the hindpaw reflex facilitation produced by tail heat, indicating the involvement of RVM ON-cells in facilitation of this reflex. 4. These data demonstrate that RVM neurons respond in a consistent manner to noxious stimuli whether applied for a brief or prolonged time: ON-cell activity increases and OFF-cell activity decreases. Moreover, the activation of RVM ON-cells produced by a noxious stimulus is sufficient to enhance some nocifensor reflexes, whereas neural structures other than the RVM appear to mediate the antinociceptive effects produced by a prolonged noxious stimulus.

Afferent Pathways↗
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↗