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Biomedical subjects

P M Dougherty

Publications and source records attributed to P M Dougherty.

At least 55 records · Page 3Linked to original sources
PubMed1997

Correlation of effects of general anesthetics on somatosensory neurons in the primate thalamus and cortical EEG power.

The effects of two types of general anesthetic on the neurophysiological properties of the primate somatosensory thalamus were correlated with effects on frontal cortex electroencephalographic (EEG) power and spectral properties. Graded doses of the intravenous agent methohexital sodium (METH) were studied in 12 cells in three monkeys on a halothane baseline anesthetic. Low doses of METH (0.2-1.0 mg/kg) produced a reduction of EEG power but had no effects on spontaneous or evoked thalamic activity. EEG power showed maximal attenuation after 2.0 mg/kg METH, whereas decreases in thalamic activity were first noted over a similar moderate dose range (2.0-5.0 mg/kg). The physiological parameter most sensitive to METH was the spontaneous activity, which showed initial changes in rate and moderate doses followed by marked inhibition at higher doses. Finally, the high dose of METH (10.0 mg/kg) produced marked reduction in all neurophysiological parameters with recovery over the following 30-45 min. The effects of the volatile anesthetic halothane were studied on 15 cells in four monkeys anesthetized with pentobarbital sodium. The low dose of halothane (0.25%) produced a facilitation of responses to cutaneous stimuli as well as decrease in the rate and burst patterns in the spontaneous activity. The power in the EEG was not affected at this concentration. The responses of the cells to the mechanical stimuli at moderate doses (0.5-1.0%) of halothane returned to the baseline magnitude, whereas spontaneous activity remained unaffected compared with initial effects. EEG power was reduced by 1% halothane. Finally, all neurophysiological parameters showed profound reduction at the highest halothane concentrations (2.0-3.0%) with recovery over the next 30-45 min. In conclusion, the two classes of anesthetics most commonly used for acute neurophysiological studies in the primate show well-defined thresholds at which changes in the response properties of thalamic neurons are produced. This threshold for the barbiturates and halothane can be predicted by monitoring of cortical EEG.

Adjuvants, Anesthesia↗
PubMed1997

Human thalamic nucleus mediating taste and multiple other sensations related to ingestive behavior.

Until now, taste was the only primary sensory modality for which the human central nervous system pathways were unknown. We report sensations evoked by stimulation at microampere current levels in the region of the human thalamic nucleus (ventralis caudalis parvocellularis internis) corresponding to the monkey taste relay nucleus. Stimulation in this region during awake neurosurgical procedures evoked special visceral/somatic (taste/pungent smell), general visceral (fullness of a hollow viscus), as well as painful and nonpainful general somatic sensations. General somatic or visceral sensation was evoked by stimulation at 80% of sites where special visceral/somatic sensation was evoked. These results suggest that primate taste relay mediates multiple sensations in addition to taste.

Brain Mapping↗
PubMed1996

Evidence that excitatory amino acids mediate afferent input to the primate somatosensory thalamus.

Neurons in and posterior to the primate sensory nucleus of the thalamus (VPL) were tested for excitation by iontophoretically applied excitatory amino acid agonists. In addition, in several cells the effects of iontophoretically applied excitatory amino acid antagonists on the responses to cutaneous stimuli were examined. All neurons showed responses to all agonists. The responses of several neurons to cutaneous stimuli were attenuated or blocked by local administration of receptor antagonists. These results provide initial evidence that somatosensory responses of neurons in the primate thalamus are mediated by excitatory amino acids.

Afferent Pathways↗
PubMed1996

Effects of carbon dioxide, fertilization, and irrigation on photosynthetic capacity of loblolly pine trees.

Branches of nine-year-old loblolly pine trees grown in a 2 x 2 factorial combination of fertilization and irrigation were exposed for 11 months to ambient, ambient + 175, or ambient + 350 micro mol mol(-1) CO(2). Rates of light-saturated net photosynthesis (A(max)), maximum stomatal conductance to water vapor (g(max)), and foliar nitrogen concentration (% dry mass) were assessed monthly from April 1993 until September 1993 on 1992 foliage (one-year-old) and from July 1993 to March 1994 on 1993 foliage (current-year). Rates of A(max) of foliage in the ambient + 175 CO(2) treatment and ambient + 350 were 32-47 and 83-91% greater, respectively, than that of foliage in the ambient CO(2) treatment. There was a statistically significant interaction between CO(2) treatment and fertilization or irrigation treatment on A(max) on only one measurement date for each age class of foliage. Light-saturated stomatal conductance to water vapor (g(max)) was significantly affected by CO(2) treatment on only four measurement dates. Light-saturated g(max) in winter was only 42% of summer g(max) even though soil water during winter was near field capacity and evaporative demand was low. Fertilization increased foliar N concentration by 30% over the study period when averaged across CO(2) treatments. During the study period, the ambient + 350 CO(2) treatment decreased average foliar N concentration of one-year-old foliage in the control, irrigated, fertilized and irrigated + fertilized plots by 5, 6.4, 9.6 and 11%, respectively, compared with one-year-old foliage in the corresponding ambient CO(2) treatments. The percent increase in A(max) due to CO(2) enrichment was similar in all irrigation and fertilization treatments and the effect persisted throughout the 11-month study period for both one-year-old and current-year foliage.

Journal Article↗
PubMed1995

Stimulation in the human somatosensory thalamus can reproduce both the affective and sensory dimensions of previously experienced pain.

Thalamic structures involved in the unpleasant emotional or affective aspect of pain are poorly understood. We now describe studies of the region of the thalamic principal somatosensory nucleus (Vc) performed before thalamotomy for tremor in a patient who also had panic disorder. Microstimulation in the region posterior to Vc evoked chest pain, including a strong affective dimension, almost identical to that occurring during his panic attacks, as measured using a questionnaire. Results in our other patients indicate that stimulation-associated pain with a strong affective dimension occurred only in those patients who had previously experienced spontaneous pain with a strong affective component. These results are consistent with stimulation-evoked activation of limbic structures, which are connected through cortex with the region posterior to Vc and involved in the affective dimension of pain through conditioning by previous experience.

Adult↗
PubMed1994

A population of cells in the human thalamic principal sensory nucleus respond to painful mechanical stimuli.

A population of neurons located in the cutaneous core of the principal sensory nucleus of human thalamus (ventralis caudalis, Vc) has been identified that had their maximal response to mechanical stimuli which were perceived as painful by the patients involved. None of these cells responded to painful thermal stimuli. The graded responses of these cells to mechanical stimuli extending into the painful range suggest they both mediate acute pain in response to mechanical stimuli and participate in mechanical hyperalgesia.

Electric Stimulation↗
PubMed1994

GFAP expression in lumbar spinal cord of naive and neuropathic rats treated with MK-801.

The objective of the present investigation was to determine if baseline glial fibrillary acidic protein (GFAP) expression and the increases in GFAP expression induced by chronic constriction of the sciatic nerve were modified by the specific N-methyl-D-aspartate (NMDA) receptor antagonist MK-801. Changes in immunohistochemical staining densities of GFAP within the L4 spinal cord were quantified and compared in three groups of animals: (1) nonneuropathic rats, (2) nondrug-treated neuropathic rats, and (3) neuropathic rats treated for 7 days with MK-801. The results indicate that baseline GFAP staining density in naive animals is dependent on NMDA receptor activity and that an ongoing NMDA-dependent signal is, at least in part, responsible for the increase in GFAP observed following peripheral nerve injury.

Animals↗
PubMed1994

The effect of trans-ACPD, a metabotropic excitatory amino acid receptor agonist, on the responses of primate spinothalamic tract neurons.

The responses of primate spinothalamic tract (STT) neurons to innocuous and noxious mechanical stimuli applied to the skin can be enhanced for more than an hour following prolonged noxious stimulation. This increased responsiveness is thought to reflect sensitization of dorsal horn neurons and may help account for secondary hyperalgesia and mechanical allodynia. The proposal that central sensitization is due to the activation of second messenger system was tested in this study by examining the effect of trans-ACPD (trans-D,L-1-amino-1,3-cyclopentanedicarboxylic acid), an agonist of metabotropic excitatory amino acid (EAA) receptors, introduced into the dorsal horn by microdialysis. A low dose of trans-ACPD resulted in an increase in the responses of STT cells to an innocuous mechanical stimulus (BRUSH), but no increase in the responses to noxious mechanical and thermal stimuli or in the excitation produced by iontophoretically applied EAAs. A high dose of trans-ACPD caused a transient increase in background activity, but no change in the responsiveness of spinothalamic cells to any of the test stimuli. It is concluded that low doses of trans-ACPD can selectively enhance transmission through interneuronal pathways mediating tactile inputs to spinothalamic cells.

Action Potentials↗
PubMed1994

Movement of respiratory CO(2) in stems of loblolly pine (Pinus taeda L.) seedlings.

Temperature-independent fluctuations in stem CO(2) efflux were measured in Pinus taeda L. seedlings. Stem CO(2) efflux was measured during high and low transpiration rates, high and low net photosynthesis rates, and normal and interrupted substrate supply conditions. Stem CO(2) efflux rates were an average of 6.7% lower during periods of high transpiration compared to periods of low transpiration. This difference in stem CO(2) efflux rates was not due to water stress. The most likely cause was movement of respiratory CO(2) in the transpiration stream. Interruption of substrate supply to the stem by phloem girdling reduced stem CO(2) efflux rates. Increasing net photosynthesis rates from low to high had no effect on stem CO(2) efflux, but decreasing net photosynthesis from high to low caused relatively small reductions in stem CO(2) efflux. These results indicate that diurnal changes in net photosynthesis rate may play a small role in temperature-independent afternoon depressions of stem CO(2) efflux. The transport of respiratory CO(2) by the transpiration stream compromises measurements of woody tissue respiration obtained by commonly accepted gas exchange techniques. This phenomenon could also affect measurement of leaf net photosynthesis and branch woody tissue respiration.

Journal Article↗
PubMed1994

The effect of phorbol esters on the responses of primate spinothalamic neurons to mechanical and thermal stimuli.

1. Sensitization of dorsal horn neurons is thought to play an important role in pain perception, secondary hyperalgesia, and allodynia. Recent experimental evidence suggests that the sensitization of dorsal horn neurons is induced by combined increased release of excitatory amino acids and peptides in the spinal cord dorsal horn from nociceptive primary afferents due to an injury-caused barrage of impulses. We tested the hypothesis that protein kinase C (PKC) is involved as a second messenger in this process of neuronal sensitization. To activate PKC, infusion of a phorbol ester [12-O-tetradecanoylphorbol-13-acetate (TPA)] into the dorsal horn through a microdialysis fiber was used. During TPA infusion the background activity of spinothalamic (STT) neurons increased substantially. After TPA application, while the background activity of the STT neurons was still increased, the responses evoked by either innocuous or noxious mechanical stimulation of the cutaneous receptive field did not change from the control level. However, 1 h after TPA administration the background activity returned to the control level and responses to innocuous mechanical stimuli were significantly elevated. The responses of STT cells to noxious heat and noxious mechanical stimuli did not change significantly after TPA administration. When a phorbol ester that does not activate PKC was applied (alpha-TPA), no significant changes in background or evoked activity of STT cells were observed. Our results provide evidence that PKC may play an important role in the process of sensitization of dorsal horn neurons to innocuous mechanical stimuli.

Animals↗
PubMed1994

Neurokinin 1 and 2 antagonists attenuate the responses and NK1 antagonists prevent the sensitization of primate spinothalamic tract neurons after intradermal capsaicin.

1. Activation of neurokinin receptors contributes to the excitation of many dorsal horn neurons by cutaneous sensory stimuli, particularly noxious stimuli. In the present study we investigate the role of neurokinin receptors in the activation of primate spinothalamic tract (STT) neurons by cutaneous mechanical stimuli and by intradermal injection of capsaicin. This was done by testing the responses of these neurons to a battery of cutaneous stimuli before and during infusion by microdialysis of antagonists selective for NK1 and NK2 receptors. 2. The NK1 receptor antagonists cis-3-(2-methoxybenzyl-amino-2-benzhydrylquinuclidine (CP96345) and D-Pro9-[Spiro-y-lactam]-Leu10,Trp11)-Physalaemin(1-11) (GR82334) did not significantly reduce the responses of STT cells to mechanical stimulation of the skin. Both NK1 antagonists did, however, produce a significant reduction in the responses of STT neurons to an intradermal injection of capsaicin. Finally, despite having no effects on responses to mechanical stimuli, both NK1 antagonists prevented the sensitization of the responses to cutaneous stimuli that is usually observed after intradermal injections of capsaicin. 3. The NK2 selective antagonists PhCO-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (GR98400) and [Tyr5,D-Trp6,8,9,Lys10]-NKA (4-10) (MEN10376) had effects very similar to those of the NK1 antagonists, but with an important difference. Neither NK2 antagonist affected the responses of STT neurons to noxious or innocuous mechanical stimulation of the skin, but they did reduce the responses to intradermal capsaicin injections. These compounds failed to prevent capsaicin-induced sensitization. In fact, cells exposed to GR98400 or MEN10376 showed unusually sustained increases in the responses to mechanical stimuli after the first capsaicin injection, suggesting that these compounds actually induced sensitization. 4. These results support the contention that both neurokinin receptors participate in the processing of nociceptive information in the dorsal horn, especially responses to strong stimuli such as intradermal injection of capsaicin. NK1 receptors are also involved in the sensitization of STT neurons after peripheral injury. A clearer understanding of the role of NK2 receptors in sensitization requires further studies with improved antagonists.

Animals↗
PubMed1993

The endogenous lectin RL-29 is transynaptically induced in dorsal horn neurons following peripheral neuropathy in the rat.

Neurons containing immunoreactivity to the endogenous lactose-binding lectin, RL-29, were examined in the L4 segment of the spinal cord of rats with an experimental neuropathy. The cells appeared by 5 days and were also present at 14 and 28 days postoperatively. All neurons were found in the dorsal horn ipsilateral to the injury. The neurons were multipolar and the reaction product revealed the morphology of the primary and secondary dendrites and some axons. Most of the neurons were located in the reticulated region of the dorsal horn, corresponding to Rexed's lamina V. In 14-day neuropathy animals treated with the NMDA-receptor antagonist MK-801, the number of RL-29 cell profiles observed was significantly reduced. Double labeling experiments revealed that spinothalamic tract neurons did not contain RL-29. The results suggest that the neuropathic injury produces a long term, transynaptic change in a subpopulation of dorsal horn neurons, that is mediated by excitatory amino acid transmitters acting at NMDA receptors.

Animals↗
PubMed1993

Quantitative analysis of substance P and calcitonin gene-related peptide immunohistochemical staining in the dorsal horn of neuropathic MK-801-treated rats.

An animal model of peripheral neuropathy resulting in a unilateral hyperalgesia has recently been developed. The N-methyl-D-aspartate (NMDA) antagonist MK-801 reduces the thermal hyperalgesia observed in this model. The goal of the present study was to determine whether the immunohistochemical changes in dorsal horn peptides shown by neuropathic animals could also be modified by MK-801. Changes in immunostaining densities of substance P (SP) and calcitonin gene-related peptide (CGRP) within the spinal cord of untreated (reference population) neuropathic rats and that of neuropathic rats treated for 7 days with MK-801 were quantified and compared. The reference neuropathic animals demonstrated thermal hyperalgesia and an ipsilateral decrease in SP staining density without an accompanying change in CGRP staining density. MK-801-treated animals showed a dose-dependent attenuation of the thermal hyperalgesia. The expected ipsilateral decrease in SP was prevented in neuropathic animals treated with a low dose (0.5 mg/kg) of MK-801, while a higher dose of MK-801 (1 mg/kg) resulted in an increase in SP staining ipsilateral to the injury. MK-801 treatment in naive rats caused a global increase in both SP and CGRP staining in the dorsal horn. However, this global increase failed to mask the changes in staining density in neuropathic animals following MK-801 treatment. The results suggest a functional interaction between excitatory amino acids (EAAs) and SP, with activation of NMDA receptors mediating depletion of SP in neuropathic animals. It is suggested that SP-containing interneurons are a target of the EAAs in the dorsal horn.

Animals↗
PubMed1993

Noninvasive subthreshold auricular electrical stimulation reduces the severity of precipitated and abrupt opiate withdrawal.

The objective of this study was to use noninvasive, subthreshold auricular electrical stimulation (AES) as a treatment to reduce the severity of precipitated and of abrupt opiate withdrawal. Sixty-four male Sprague-Dawley rats were divided into six groups. The first three groups were used to study the effects of AES on naloxone-precipitated withdrawal; the other three groups were used to examine the influence of AES on abrupt withdrawal. Morphine dependence was induced by multiple injections of the drug on an incremental staircase dosage regimen for 6 days. The results obtained from first three groups show that AES reduced the severity of the withdrawal signs precipitated by naloxone injection (0.5 mg/kg SC) by more than 75% (p < 0.01). The observations obtained from the other three groups show that AES reduced the severity of abrupt withdrawal for at least 4 h as assessed by measuring the locomotor behavior of the animals. This study demonstrates that noninvasive subthreshold AES is effective in reducing the severity of precipitated and of abrupt opiate withdrawal.

Animals↗
PubMed1992

Differential influence of local anesthetic upon two models of experimentally induced peripheral mononeuropathy in the rat.

Neuropathic pain remains a major complication of various forms of injury to peripheral nerves in humans. Recently, 2 models of peripheral mononeuropathy in the rat have been described which closely resemble the human condition. Bennett and Xie3 described one model induced by the placement of 4 loose ligatures around the entire sciatic nerve; Seltzer et al. have described a second model produced by the placement of a tight ligature around one-third to one-half of the sciatic nerve. It is the purpose of this work to compare the effect of these injuries on the time course and magnitude of hyperalgesia as measured by paw withdrawal latency to a radiant heat stimulus. In addition, to evaluate the hypothesis that neuropathic pain develops as a result of injury-associated discharges, some injuries were induced following anesthesia of the sciatic nerve. Our results show that the partial constriction neuropathy (PCN) described by Bennett and Xie3 develops in a faster time frame than that produced by the tight ligature, or partial transection neuropathy (PTN), described by Seltzer and co-workers. In addition, the PCN shows a reduction in both the duration and magnitude of behavioral hyperalgesia obtained for those animals in which local anesthetic (lidocaine) was applied to the sciatic nerve, while the PTN does not show this sensitivity. The data suggest that injury-related discharge is one important factor contributing to the generation of hyperalgesia in the PCN model. The mechanism(s) responsible for the generation of hyperalgesia in the early stages of the PTN model are not lidocaine-sensitive.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics, Local↗
PubMed1992

Responses of spinothalamic tract cells to mechanical and thermal stimulation of skin in rats with experimental peripheral neuropathy.

1. Responses of spinothalamic tract (STT) neurons to mechanical and thermal stimulation of skin were recorded under urethane and pentobarbital anesthesia in 12 control rats and in 20 rats with experimental neuropathy. Activity of the STT cells in neuropathic rats was recorded 7, 14, and 28 days after inducing the neuropathy by placing four loose ligatures on the sciatic nerve. 2. All neuropathic animals showed guarding of the injured hindpaw and a shorter withdrawal latency from a radiant heat source of the neuropathic hindpaw than that of the sham-operated paw. 3. STT neurons in neuropathic animals showed the most profound changes 7 and 14 days after the nerve ligation. When compared with STT cells in unoperated animals, approximately half of the neurons had high background activity, responses to innocuous stimuli represented a larger percentage of the total evoked activity in wide dynamic range neurons, and the occurrence and magnitude of afterdischarges to mechanical and thermal stimuli were increased. 4. The mean threshold temperatures of heat-evoked responses of the STT cells in neuropathic animals were not different than those of cells from control animals. However, in neuropathic rats, cells reacting to small heat stimuli usually already had afterdischarges. 5. The increase in the background activity of STT cells is consistent with behavioral observations of spontaneous pain in this model of experimental neuropathy. Furthermore, the afterdischarges of STT cells may parallel the prolonged paw withdrawal in response to noxious stimuli that is seen in these animals and that is evidence for hyperalgesia. However, there was no indication of a lowered threshold for thermal stimuli as might be expected if the animals have thermal allodynia. Mechanical allodynia may have resulted from a relative increase in responsiveness to innocuous mechanical stimuli. However, responses to noxious mechanical stimuli were reduced compared with control, at least at 28 days after the ligation. Peripheral and central mechanisms responsible for the changes in responses of STT cells in neuropathic animals are suggested.

Animals↗