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Biomedical subjects

D J Mayer

Publications and source records attributed to D J Mayer.

At least 91 records · Page 5Linked to original sources
PubMed1982

Opiate vs non-opiate footshock-induced analgesia (FSIA): the body region shocked is a critical factor.

Previous work has demonstrated that footshock can elicit either opiate or non-opiate analgesia. The present study has demonstrated that one critical factor determining the involvement of endogenous opioids is the body region shocked. Using 90 s shock, front paw shock produced an opiate analgesia which was significantly antagonized by as little as 0.1 mg/kg systemic naloxone and morphine tolerance. In the latter experiment, a parallel recovery of the analgesic potencies of both front paw shock and morphine was observed following 2 weeks of opiate abstinence. In contrast, hind paw shock produced a non-opiate analgesia which failed to be attenuated by 20 mg/kg systemic naloxone and showed no cross-tolerance to morphine. Since identical shock parameters were used for front paw and hind paw shock in the systemic naloxone experiments, stress per se clearly cannot be the crucial factor determining the involvement of endogenous opioids in footshock-induced analgesia. These results were discussed with respect to clinical treatments of pain which utilize somatosensory stimulation.

Analgesia↗
PubMed1982

Involvement of spinal opioid systems in footshock-induced analgesia: antagonism by naloxone is possible only before induction of analgesia.

Footshock reliably produces analgesia in rats which is mediated either by opiate or non-opiate systems. It has recently been demonstrated that a critical factor determining the involvement of endogenous opioids is the body region shocked; front paw shock produces a naloxone-reversible analgesia and hind paw shock produces an analgesia which fails to be attenuated by this opiate antagonist. The present study demonstrated that a crucial opiate site for the production of front paw footshock-induced analgesia (FSIA) exists within the spinal cord. One microgram of naloxone delivered directly to the lumbosacral cord immediately prior to shock significantly attenuated this analgesia. However, the efficacy of naloxone antagonism was order-dependent in that naloxone failed to antagonize fron paw FSIA if delivered immediately after shock; naloxone could prevent but could not reverse the analgesic state. The body region shocked was again observed to be a critical factor determining the involvement of endogenous opioids since 1 microgram of spinal naloxone failed to antagonize hind paw FSIA. These results were discussed in light of recent evidence proposing a neuromodulatory role of opioids within the spinal cord.

Analgesia↗
PubMed1982

Organization of endogenous opiate and nonopiate pain control systems.

Research during the past decade has revealed the existence of neural systems that modulate pain transmission. Much of this work has focused on the role of endogenous opiate systems, but recent research indicates the involvement of nonopiate mechanisms as well. In this article, we present data demonstrating that opiate and nonopiate analgesia systems can be selectively activated by different environmental manipulations and describe the neural circuitry involved. Both neural and hormonal pathways and both opiate and nonopiate substances play roles in the complex modulation of pain transmission. The existence and description of these modulatory mechanisms have important clinical implications for the treatment of pain.

Acupuncture Therapy↗
PubMed1982

Failure of spinal cord serotonin depletion to alter analgesia elicited from the periaqueductal gray.

The effects of spinal cord serotonin depletion or combined serotonin/norepinephrine depletion on analgesia elicited by electrical stimulation of, or morphine microinjection into, the periaqueductal gray, were tested. Spinal cord serotonin was depleted by intrathecal injection of 5,7-dihydroxytryptamine (5,7-DHT), preceded by systemic desipramine, while 5,7-DHT alone was used to deplete both norepinephrine and serotonin. Selective serotonin depletion had no effect on analgesia induced by either method at 24 h, 1 week, or 2 weeks after treatment. Depletion of both monoamines had no effect on stimulation produced analgesia 24 h and one week after treatment, but produced a slight attenuation 2 and 3 weeks after treatment. In contrast, depletion of both monoamines drastically attenuated morphine analgesia 24 h after treatment. The results are discussed in relation to multiple pain inhibitory pathways.

5,7-Dihydroxytryptamine↗
PubMed1982

A transcannula method for subcortical HRP gel implants: inferior olive afferents in the rat.

A technique for using horseradish peroxidase in a polyacrylamide gel form for subcortical implants is described. In order to prevent uptake along the injection tract, the solid HRP gel pellet is delivered through a pre-implanted cannula to the target site. The appreciable advantages of using the HRP-transcannula technique are discussed in conjunction with a description of the afferents to the inferior olivary complex in the rat. The principal sources of afferents were the ipsilateral prerubral parafascicular nucleus, contralateral lateral cerebellar nucleus and dorsal column nuclei.

Acrylic Resins↗
PubMed1981

Identification and somatotopic organization of nuclei projecting via the dorsolateral funiculus in rats: a retrograde tracing study using HRP slow-release gels.

Horseradish peroxidase (HRP) in slow-release gel was unilaterally implanted in the transected dorsolateral funiculus (DLF) of either cervical, midthoracic, lumbar or sacral spinal cord levels of adult male rats. Cell mappings were made of all brain areas projecting through the DLF. Following cervical implants, dense labelling was observed within a band along the dorsolateral border of the inferior olive, locus coeruleus, the paralemniscal reticular formation, the mesencephalic central gray, the red nucleus and the paraventricular nucleus of the hypothalamus. The DLF projection from the central gray consisted of a rostrocaudal line of cells extending from the level of the mesen-/diencephalic junction to the rostral red nucleus. The somatotopic organization of labelled nuclei was assessed by comparing the pattern of filled cells following HRP implants at various cord levels. The potential role of these areas in pain modulation was discussed in light of their descending projections through the DLF of the spinal cord.

Afferent Pathways↗
PubMed1981

Blockade by naltrexone of analgesia produced by stimulation of the dorsal raphe nucleus.

Naloxone blockade of stimulation-produced analgesia in the rat is partial and variable. In the present study the effectiveness of the long-acting narcotic antagonist naltrexone is examined. Bipolar stainless steel electrodes were implanted in the dorsal raphe nucleus or ventral periaqueductal gray matter of male rats. Analgesia produced by electrical stimulation was tested by the tail flick method before and twenty min following the administration of saline or naltrexone. Saline administered IP failed to alter the analgesic response. Following naltrexone the degree of analgesia was reduced by a mean of 79% for IV injection (3.7 mg/kg) and by means of 26%, 52%, 81% and 83% for IP administration of 0.3, 1.0, 3.0 and 10 mg/kg, respectively. These results confirm the participation of opiate mechanisms in stimulation-produced analgesia, and indicate that, under certain circumstances, only opiate mechanisms are involved.

Analgesia↗
PubMed1980

The somatotopic organization of the nucleus raphe magnus and surrounding brain stem structures as revealed by HRP slow-release gels.

Horseradish peroxidase (HRP) in slow-release gel was unilaterally implanted in the dorsal lateral funiculus (DLF) of either cervical, midthoracic, lumbar or sacral spinal cord levels of adult male rats. Complete mappings and cell counts were made of HRP-filled cells from the level of the rostral trapezoid body caudal to the inferior olive. Following cervical or midthoracic placements, labelled cells often formed a continuous band surrounding the medial, dorsal and lateral aspects of the ipsilateral pyramid and extending into the ventral region medial to the facial nucleus and lateral to the pyramid. It appears that this population of HRP-filled cells in the nucleus raphe magnus (NRM) and reticularis magnocellularis (Rmc) corresponds to the serotonergic cell group B3 of Dahlström and Fuxe. In lumbar and sacral cases, there was a noticeable difference both in the pattern and number of labelled cells, with fewer labelled cells and greater tendency for a 'gap' to occur in the population of cells midway over the pyramid. Based on the patterns of labelling and a review of the literature, its appears that the actual functional unit involved in the descending control of nociception may be the combined population of Rmc and NRM.

Animals↗
PubMed1979

Inhibition of spinal cord interneurons by narcotic microinjection and focal electrical stimulation in the periaqueductal central gray matter.

Single cell evoked activity was recorded from spinal cord interneurons in rats prepared with microinjection cannulae or stimulating electrodes in the periaqueductal central gray matter (PAG). Morphine microinjections (4-16 microgram) inhibited the response evoked by a noxious stimulus in 55% of the wide dynamic range neurons tested. Microinjections of etorphine (0.25-0.5 microgram) inhibited 82% of the nociceptive neurons tested. Neither drug inhibited neurons which responded only to innocuous mechanical stimulation. The inhibition of wide dynamic range neurons produced by narcotic microinjection was antagonized by naloxone (1 mg/kg, i.p.) in 7 of 11 cases. Control experiments indicated that the effects obtained with microinjections could not be attributed to the drugs' diffusion to the spinal cord. Focal electrical stimulation of the PAG inhibited the responses to noxious stimuli of 60% of wide dynamic range neurons but was without effect on the responses of neurons that were activated only by innocuous stimuli. These experiments directly demonstrate that narcotic analgesics restricted to an intracerebral site of action activate a neural system which preferentially inhibits the responses of spinal cord wide dynamic range neurons to noxious stimuli. The system has a specificity for nociceptive input since non-nociceptive neurons were unaffected. Directly comparable results were produced by electrical stimulation of the PAG, supporting the concept that stimulation and narcotics modulate the transmission of nociceptive information by similar mechanisms.

Animals↗
PubMed1978

Behavioral and physiological studies of non-narcotic analgesia in the rat elicited by certain environmental stimuli.

These experiments characterized the analgesia resulting from exposure to certain noxious and/or stressful manipulations. Rats exposed either to electric grid shock (0.35-2.0 mA for 10-30 sec) or to 5 min of presumably non-painful centrifugal rotation (about 7.0 transverse g's) were analgesic as measured by tail-flick, hot plate and responses to applications of a calibrated paw pinch or alligator clip. Analgesia produced by shock (SA) or centrifugal rotation (RA) persisted after termination of these manipulations. Neither SA nor RA were attended by generalized sensory, attentional or motoric deficits. Intraperitoneal injection of hypertonic saline also increased tail-flick latencies. Exposure to brief ether anesthesia or horizontal oscillation, both of which have been reported to increase ACTH secretion (a commonly used indicator of stress), did not produce analgesia as measured by the tail-flick test. The use of classical conditioning procedures to pair shock with environmental stimuli resulted in increased tail-flick latencies. The narcotic antagonist naloxone (1 mg/kg, i.p.) did not reduce the tail-flick inhibition produced by shock, rotation, hypertonic saline or classical conditioning. Chlordiazepoxide (5 mg/kg, i.p.) also failed to antagonize the increased tail-flick latencies produced by shock or conditioning. Tail-flick inhibition produced by shock or rotation was markedly reduced by complete spinal cord transection at thoracic levels. These results suggest that: (1) the selective modulation of nociceptive input at the level of the spinal cord can be mediated by a supraspinal system or systems physiologically distinct from those involved in analgesia produced by the administration of opiates; (2) non-narcotic modulation of nociceptive input occurring within the spinal cord can be learned by exposure to classical conditioning procedures; and (3) noxious stimuli are sufficient but not necessary to produce a non-narcotic analgesia; stress alone, however, is not always sufficient to produce this analgesia.

Analgesia↗
PubMed1978

Differential effects of spinal cord lesions on narcotic and non-narcotic suppression of nociceptive reflexes: further evidence for the physiologic multiplicity of pain modulation.

These studies examined the effects of bilateral lesions of the dorsolateral funiculus (DLF) of the rat spinal cord on the inhibition of a nociceptive reflex produced either by a systemic injection of 4 mg/kg of morphine or by a 20 sec exposure to 1.0 mA of transcutaneous electric shock. Reflex inhibition was quantified and analgesia inferred by use of a modified version of the D'Amour-Smith tail-flick test. Lesions which included only the DLF reduced morphine-produced analgesia (MA) by 73% but had no effect on shock-produced analgesia (SA) observed in the same rats. Baseline tail-flick latencies of this group were not affected by the lesions. Control lesions restricted to the dorsal columns attenuated neither MA nor SA. Lesions which included both the dorsal columns and DLF did not affect SA and produced no greater reduction in MA than lesions of the DLF alone. Previous work indicates that both MA and SA result, at least in part, from supraspinal activity. The current data indicate that: (1) supraspinal modulation participating in two different types of analgesic induction involves separate descending spinal pathways and (2) the maximal expression of analgesia produced by administration of narcotics requires the integrity of a supraspinal neural system projecting in the DLF.

Animals↗
PubMed1977

Evaluation of brain function in severe human head trauma with multimodality evoked potentials. Part 1: Evoked brain-injury potentials, methods, and analysis.

Methods for obtaining multimodality evoked potentials, somatosensory, visual, auditory, and auditory brain-stem potentials in patients with severe head trauma are described. A method of analyzing abnormal multimodality evoked potentials (graded evoked brain-injury potentials) is proposed that defines the degree of abnormality of the electrophysiological data and expresses it simply in four grades per modality. Data from 20 normal subjects are given for comparison with the abnormal data obtained from 51 patients with head trauma.

Acoustic Stimulation↗