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G H Duncan

Publications and source records attributed to G H Duncan.

At least 37 records · Page 2Linked to original sources

Thalamic VPM nucleus in the behaving monkey. II. Response to air-puff stimulation during discrimination and attention tasks.

1. Single-unit activity was recorded in the ventral posterior medial (VPM) thalamic nucleus of awake monkeys while they performed detection and discrimination tasks involving tactile air-puff stimuli presented to the face. Neuronal responsiveness was compared directly with the monkey's discriminative performance. In addition, neuronal activity was compared when the monkey's attention was directed to the air-puff stimulus and when it was directed to a concurrent visual stimulus. 2. Neurons responding to the air-puff stimuli were classified as slowly adapting (SA), rapidly adapting (RA), inhibitory (IN), or multimodal (MM), according to their responses to manual and thermal stimulation, as well as their adaption rates to the air puff. Of 47 neurons responsive to air-puff stimulation and studied extensively in the behavioral task, 14 were classified as RA, 15 as SA, 6 as IN, and 12 as MM. The 12 MM neurons were so classified because, in addition to air puff, they responded to noxious heat, innocuous cooling, or noxious pinch. 3. Neurons from each class had restricted contralateral receptive fields localized within one division of the trigeminal nerve. There was no systematic difference in receptive-field size among groups. 4. A prominent difference in tactile responsiveness of MM neurons was response latency. Although the mean latency for RA, SA, and IN neurons was not significantly different (6.1, 9.1, and 12.2 ms, respectively), the mean latency for MM neurons was significantly longer than that for each of the other neuronal categories (28.8 ms; Ps < 0.001). These data suggest that the excitatory tactile afferent input to MM neurons is different from that to low-threshold neurons. 5. For RA, SA, and MM neurons the frequency of the neuronal discharge evoked by the air-puff stimulation was proportional to the intensity of the air puff. Thus responses of each neuronal class coded air-puff stimulus intensity. 6. The monkeys' ability to detect air-puff stimuli of various intensities was compared with the frequency of neuronal responses to those stimuli. Both the percent success in detecting differences in air-puff intensity and the detection latency were highly correlated with neuronal response frequency. The responses of all three excitatory neuronal categories corresponded well with the monkey's performance. Thus any or all of RA, SA, and MM neurons could play a role in the discrimination of air-puff intensities.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Thalamic VPM nucleus in the behaving monkey. III. Effects of reversible inactivation by lidocaine on thermal and mechanical discrimination.

1. The present study evaluates the necessity of the ventroposterior medial thalamic nucleus (VPM) for discrimination of the intensity of noxious heating, innocuous cooling, and innocuous tactile (airpuff) stimulation of the maxillary skin. 2. Two rhesus monkeys were trained to detect small differences (< 1.0 degrees C) in the intensity of noxious heat (near 46 degrees C) and innocuous cold (near 30 degrees C) as well as differences in the force of an airpuff applied to the skin over the maxilla. As a control the monkeys also detected small differences in the intensity of a white light. Lidocaine hydrochloride (2%) was microinjected into regions of thalamus where single-unit recordings had identified neuronal responses to the noxious heating and/or cooling stimuli. The effectiveness of the anesthetic blockade was monitored by multiunit recordings using microelectrodes positioned 1-3 mm from the orifice of the injection cannula. The monkey's ability to detect near-threshold changes in stimulus intensity was compared before and after each injection. 3. During six experimental sessions, single injections of 1-4 microliters lidocaine near the dorsomedial border of VPM did not significantly alter the monkey's ability to detect small changes in the intensity of noxious heat, cool, airpuff, or visual stimuli despite neurophysiological evidence that spontaneous neuronal activity was blocked within parts of VPM. 4. During three experiments, dual simultaneous microinjections of lidocaine (delivered through 2 microcannulae separated by approximately 1 mm) resulted in profound deficits in noxious heat discrimination, with lesser deficits in cool and airpuff discrimination; visual discrimination was never altered. Monitoring of adjacent microelectrodes revealed that although activity ventral to the injection sites was blocked, activity in medial thalamic nuclei, implicated in nociceptive processing, was probably not altered by these injections. 5. These data suggest that VPM is important for the perception of noxious and innocuous thermal stimuli as well as for the perception of tactile stimuli. However, considering the ineffectiveness of small single microinjections of lidocaine, it appears that some critical proportion of VPM must be inactivated to disrupt thermal or tactile discrimination, possibly because of overlapping receptive field properties of neurons in different areas of the nucleus.

Animals↗

A psychophysical comparison of sensory and affective responses to four modalities of experimental pain.

It is generally accepted that the sensory and affective components of pain may be differentially associated with various acute and chronic diseases, and that some treatment regimens are best directed toward certain aspects of the pain experience. In addition, experimental animal models have been described that presume to assess either the sensory-discriminative aspects of phasic pain or the affective responses associated with tonic pain. The present psychophysical experiment directly compares the perceived intensity and unpleasantness of sensations evoked by four types of experimental noxious stimuli: contact heat, electric shock, ischemic exercise, and cold-pressor pain. A novel pain measurement technique is described that incorporates unbounded magnitude-estimation/category scales; this technique allows precise ratio responses, while minimizing within- and between-subject variability. We observe that, relative to the perceived intensity of the individual stimuli, subjects consistently differentiate among the degrees of unpleasantness evoked by the four stimulus modalities. Ischemic exercise and cold-pressor pain evoke higher estimates of unpleasantness, and thus may better mimic the pain of chronic disease. The relative unpleasantness produced by contact heat is significantly less than that of the other modalities tested, and therefore contact heat stimuli may be ideally suited for assessing sensory-discriminative aspects of pain perception. Possible neurophysiological mechanisms underlying the observed differences in perceived unpleasantness are discussed in relation to the growing body of literature concerning tonic and phasic pain stimuli.

Adult↗

Multiple representations of pain in human cerebral cortex.

The representation of pain in the cerebral cortex is less well understood than that of any other sensory system. However, with the use of magnetic resonance imaging and positron emission tomography in humans, it has now been demonstrated that painful heat causes significant activation of the contralateral anterior cingulate, secondary somatosensory, and primary somatosensory cortices. This contrasts with the predominant activation of primary somatosensory cortex caused by vibrotactile stimuli in similar experiments. Furthermore, the unilateral cingulate activation indicates that this forebrain area, thought to regulate emotions, contains an unexpectedly specific representation of pain.

Adult↗

The effects of dorsal column stimulation on measures of clinical and experimental pain in man.

Despite the extensive use of dorsal column stimulation (DCS) for the control of various chronic pain conditions, most clinicians report only modest success rates. Surprisingly, there has been little placebo-controlled investigation of its efficacy for altering either clinical or experimental pain perception. The current study compared the effects of DCS to placebo stimulation on clinical pain perception, perceived intensity of painful heat stimuli and visual stimuli, and the discrimination of small changes in noxious heat intensity and in light intensity. We found that DCS, but not placebo stimulation, significantly altered ratings of spontaneous clinical pain as well as those of painful cutaneous heat. In addition, heat discrimination thresholds were increased by DCS, but not placebo. On the other hand, DCS had no effect on ratings of visual stimulus intensity nor on visual discrimination, suggesting that the DCS modulation of pain perception was not due to a general change in attention. These data indicate that DCS significantly alters pain transmission in humans. Nevertheless, the relatively small reduction in clinical pain (less than 30%) must be weighed against the invasive nature of electrode implantation.

Adult↗

Modulation of heat pain perception by high frequency transcutaneous electrical nerve stimulation (TENS).

Although many studies have indicated that high frequency nonpainful transcutaneous electrical nerve stimulation (TENS) reduces clinical pain, controlled studies of the modulation of experimental pain by TENS have produced conflicting results. This study evaluated the effect of high frequency nonpainful TENS on heat pain perception using a model that we have previously shown to be sensitive to other nonpharmacological analgesic treatments. We found that TENS significantly reduced subjects' ratings of painful and near painful heat stimuli (43-51 degrees C) (p = 0.01) and increased the pain threshold from 46.7 to 47.9 degrees C (p = 0.002). Placebo stimulation had no effect on the subjects' ratings or on their pain thresholds. Furthermore, TENS did not alter subjects' ratings of visual stimuli, indicating that the analgesic effect was not due to a nonspecific distraction. These data suggest that TENS alters the perception of experimentally produced natural pain stimuli. The TENS related modulation also appears to be comparable to that produced by other nonpharmacological analgesic manipulations such as counterirritation and changes in attention.

Adult↗

Nuclear location of the 16K non-structural protein of tobacco rattle virus.

An antiserum, elicited by a synthetic peptide coupled to bovine serum albumin, reacted specifically with the non-structural 16K protein of tobacco rattle virus. The protein was detected in extracts of systemically infected Nicotiana clevelandii leaves, but only in those made with the aid of SDS, urea and 2-mercaptoethanol. Immunogold labelling of ultrathin sections showed that the protein was mainly associated with nuclei, but was also present in the cytoplasm. These observations suggest that the 16K protein binds to macromolecular components of infected cells, especially in nuclei, but do not clarify its function.

Amino Acid Sequence↗

Electrical stimulation of peripheral and central pathways for the relief of musculoskeletal pain.

One method for the treatment of chronic musculoskeletal pain involves stimulation of the peripheral or central nervous system. Such stimulation includes transcutaneous electrical nerve stimulation, dorsal column stimulation, and deep brain stimulation. This review discusses the clinical use of electrical stimulation for the relief of musculoskeletal pain, and describes the results of studies conducted in our laboratory suggesting that such stimulation reduces pain transmission along sensory-discriminative pathways.

Animals↗

The perception of painful and nonpainful stimuli during voluntary motor activity in man.

Previous studies have shown that voluntary movement diminishes the transmission of cutaneous afferent input through the dorsal column-medial lemniscal system, and also raises the threshold for detecting nonpainful, cutaneous stimuli (electrical shocks). Although there is some evidence that pain elicited by electrical stimulation is diminished during movement, no studies have tested the effect of movement on the perception of pain produced by natural stimulation. For this reason, we tested the effects of voluntary motor activity on the perception of noxious thermal stimuli in human volunteers. We first developed a motor paradigm in which the thermal stimulation could be applied to the immobile limb (isometric elbow flexion-extension). Both isometric and isotonic muscle contractions about the elbow increased the threshold for detecting weak cutaneous stimuli (electrical shocks) applied to the forearm, and to a lesser extent the detection of stimuli applied to the dorsum of the hand. Afterwards, noxious and innocuous heat stimuli were applied to the forearm during isometric contractions and at rest. Magnitude estimates for the intensity of the pain, as well as latency measures of the onset of pain, were recorded. We found no evidence that isometric motor activity diminished either the threshold for pain or the subjective intensity of the noxious and innocuous thermal stimuli. Thus, motor activity decreases the ability to detect weak low-threshold cutaneous inputs, but has no effect on the perception of warmth and heat pain.

Arousal↗

A primate model for the study of tonic pain, pain tolerance and diffuse noxious inhibitory controls.

A primate model of cold pressor pain is described in which the animal itself initiates all trials, may terminate painful stimuli at any time, and controls the duration of the experimental session, thus avoiding the inadvertent administration of intolerable pain stimuli. Pain tolerance time varies directly with stimulus intensity and is sensitive to motivational factors. This model will facilitate the study of endogenous pain-modulatory pathways and the assessment of analgesic treatments in animals.

Adaptation, Physiological↗

Sensory and affective aspects of pain perception: is medial thalamus restricted to emotional issues?

Lateral and medial thalamus are traditionally thought to have separate roles in pain processing, with lateral lemniscal regions transmitting discriminative information about location and intensity, while medial nonspecific regions are involved in emotional responses. Contrary to this view, the present study shows that some single neurons in medial thalamus of alert monkey discriminate changes in the intensity of noxious stimuli that are equal to or below the monkey's own discrimination threshold. Since these neurons are also modulated by anesthesia and attentional factors, we suggest that parts of medial thalamus may participate in both discriminative and affective dimensions of pain.

Action Potentials↗

Production of antiserum to a non-structural potyviral protein and its use to detect narcissus yellow stripe and other potyviruses.

A protein, of apparent molecular weight 72,000, was purified from experimentally infected narcissus plants with yellow stripe symptoms utilising SDS-polyacrylamide gel electrophoresis. This protein was excised from the gels and used to prepare antiserum, which reacted specifically with cytoplasmic cylindrical inclusions in ultra-thin sections of virus-infected cells and, in immunoblots, with the 72 kDa protein in preparations containing cytoplasmic inclusions. The antiserum reacted in ELISA with leaf extracts from yellow stripe diseased plants of four narcissus cultivars but not with extracts from comparable symptomless plants. In tests with extracts of plants infected with seven definitive potyviruses, reactions were obtained with bean yellow mosaic and iris mild mosaic viruses. Virus-specific reactions in dot-blot ELISA were dependent on the presence of Tween 20 in the extraction buffer. In contrast, an antiserum to the putative cytoplasmic inclusion protein of alstroemeria mosaic virus reacted only with SDS-treated leaf extracts of infected plants. In limited tests, the method of purifying cytoplasmic inclusion protein was successfully applied to four definitive potyviruses, suggesting that it may be generally applicable to potyviruses and of use for preparing antisera when purification of virus particles is difficult.

Antibodies, Viral↗

Preoperative flurbiprofen in oral surgery: a method of choice in controlling postoperative pain.

The analgesic efficacy of a single 50-mg preoperative dose of flurbiprofen was compared with ACC-30 (aspirin 375 mg, codeine 30 mg, caffeine 30 mg) and a placebo. Forty patients scheduled for the surgical removal of impacted maxillary third molars were enrolled in a double-blind, randomized study. Using a within-subject design we compared the analgesic efficacy of (1) preoperative flurbiprofen 50 mg with placebo in 20 patients, and (2) preoperative ACC-30 with placebo in 20 other patients. Using a between-group design, we then compared the analgesic efficacy of (3) each drug given preoperatively and postoperatively, and (4) each drug given postoperatively only. Patients rated 2 pain dimensions, intensity and unpleasantness, hourly for 8 hours after the presurgical dose. The results of this study indicate that better analgesia was obtained when flurbiprofen was given preoperatively compared to only after surgery. Conversely, preoperative administration of ACC-30 did not demonstrate any significant influence on postsurgical analgesia. When comparing the 2 drugs, flurbiprofen proved to be superior in providing pain relief only when it was given prior to surgery. There was no difference between them when given only after surgery. Side effects were moderate and not significantly different between patients receiving flurbiprofen and those receiving ACC-30.

Adult↗

Mechanical response properties of ventroposterior medial thalamic neurons in the alert monkey.

The properties of trigeminal cutaneous thalamic neurons were explored in alert cynomolgous monkeys to determine receptive field and response characteristics. Two monkeys received juice reward for sitting quietly while an investigator probed the monkey's face with mechanical stimuli. Extracellular single unit recordings were made from the ventroposterior medial thalamic nucleus (VPM), and mechanical response properties were evaluated for each cell having an extraoral cutaneous receptive field. Of 89 cells examined, 90% responded best to innocuous tactile stimulation, and were classified as low threshold. The other 10%, classified as wide dynamic range, showed a graded response to increasingly intense stimuli, with a maximum discharge to noxious pinch. Of the low threshold neurons, most exhibited excitatory responses, with about half being rapidly adapting and the others slowly adapting. The spontaneous activity of 11% of the low threshold neurons was inhibited by stimulation of the neuron's receptive field. There was no systematic difference in receptive field size for the various types of neurons, but the receptive fields of wide dynamic range cells were smaller than those previously observed in trigeminopthalamic neurons of the medullary dorsal horn. The wide dynamic range and inhibitory low threshold neurons were located primarily in the caudal third of VPM, while the excitatory low threshold neurons were located throughout. In summary, response characteristics of VPM neurons show more diversity in the alert monkey than has been reported in paralyzed and/or anesthetized animals.

Adaptation, Physiological↗

Sensory perception during movement in man.

The ability of subjects to perceive innocuous stimuli in the presence and absence of movement was evaluated using electrical stimulation of the skin. The subjective intensity of suprathreshold stimuli was unchanged during movement. Discrimination of small differences in the intensity of suprathreshold stimuli (difference thresholds) was also not altered by movement while, in the same subjects, detection thresholds were increased during movement of the stimulated arm. These results suggest that the elevation of detection thresholds during movement can be explained by masking. Both active and passive movement of the stimulated limb increased detection thresholds, with active movement having a slightly greater and more consistent effect than passive movement. Thus, both central and peripheral feedback factors appear to play a role in diminishing one's ability to detect weak stimuli during movement. Attention was also shown to influence performance of the detection task.

Electric Stimulation↗

Task-related responses of monkey medullary dorsal horn neurons.

Medullary dorsal horn neurons with trigeminal sensory properties have been previously shown to have additional responses associated with cues relevant to the successful execution of a behavioral task. These "task-related" responses were evoked by environmental cues but were independent of the specific stimulus parameters. We have examined further the characteristics of task-related responses in medullary dorsal horn neurons of three monkeys. Single-unit activity was recorded while the monkeys were performing behavioral tasks that required them to discriminate thermal or visual stimuli for a liquid reward. Forty-five percent (34/75) of the medullary dorsal horn neurons studied exhibited task-related activity that was significantly correlated with the stereotypical behavioral events that occurred during the tasks. Similar events occurring outside of the task produced no response. In addition to the task-related activity of these medullary dorsal horn neurons, responses to mechanical and/or thermal stimuli presented within the neuron's receptive field were demonstrated in 28 of 34 cases. These sensory responses also were evoked by the same stimuli presented outside of the behavioral task. Fifteen of the neurons with task-related responses could be activated antidromically from thalamic stimulating electrodes. Task-related responses were categorized according to their relationship to the three phases of the behavioral trial: trial initiation, trial continuation, and trial termination. Although an individual task-related response was associated with a single behavioral event, most medullary dorsal horn neurons (30/34) exhibited a reproducible pattern of task-related responses that occurred during more than one phase of the trial. Trial-initiation task-related responses were subdivided depending on their correlation with specific events that occurred within that phase of the trial. One-third of the 18 excitatory trial-initiation responses were associated with the visual stimulus that cued the monkey to begin the trial; the remaining two-thirds were associated with the monkey's press of the button that actually initiated the trial. Trial-continuation task-related responses (observed while the monkey waited for a thermal stimulus that triggered a rewarded motor response) were shown to be independent of the actual temperature of the thermal stimulus. In addition these trial-continuation task-related responses were also noted during trials without a thermal stimulus, in which the trigger cue was the onset of a light (in a visual task).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The modulation of sensory transmission through the medullary dorsal horn during cortically driven mastication.

During mastication, reflexes are modulated and sensory transmission is altered in interneurons and ascending pathways of the rostral trigeminal sensory complex. The current experiment examines the modulation of sensory transmission through the most caudal part of the trigeminal sensory system, the medullary dorsal horn, during fictive mastication produced by cortical stimulation. Extracellular single unit activity was recorded from the medullary dorsal horn, and multiple unit activity was recorded from the trigeminal motor nucleus in anesthetized, paralyzed rabbits. The masticatory area of sensorimotor cortex was stimulated to produce rhythmic activity in the trigeminal motor nucleus (fictive mastication). Activity in the dorsal horn was compared in the presence and absence of cortical stimulation. Fifty-two percent of neurons classified as low threshold and 83% of neurons receiving noxious inputs were influenced by cortical stimulation. The cortical effects were mainly inhibitory, but 21% of wide dynamic range and 6% of low threshold cells were excited by cortical stimulation. The modulation produced by cortical stimulation, whether inhibitory or excitatory, was not phasically related to the masticatory cycle. It is likely that, when masticatory movements are commanded by the sensorimotor cortex, the program includes tonic changes in sensory transmission through the medullary dorsal horn.

Animals↗