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Biomedical subjects

R Dubner

Publications and source records attributed to R Dubner.

At least 109 records · Page 6Linked to original sources

Attentional influences on noxious and innocuous cutaneous heat detection in humans and monkeys.

This study examines whether selective attention can influence sensory-discriminative aspects of nociception in humans and monkeys trained to detect innocuous and noxious thermal stimuli. Human subjects had two contact thermodes positioned bilaterally above the upper lip. Upon trial initiation both thermodes heated to either 39 degrees C, an innocuous warm temperature, or 45 degrees C, a slightly noxious temperature. After 4 to 9 sec, the temperature of one thermode increased an additional step of less than 1 degree C. Subjects released a button when they detected this second temperature increase (T2). Three types of trials were presented in order to assess the effects of spatially selective attention on thermal detection. On 40% of the trials a light correctly signaled the location of the thermode on which T2 would occur. On 10% of trials a light incorrectly signaled the location of T2. No signal was presented on the remaining trials. From the 45 degrees C base line, detection latencies were shortest in the correct signal condition, longest in the incorrect signal condition, and intermediate in the unsignaled condition. The percent of undetected T2s was greatest in the incorrect signal condition and least in the correct signal condition. From the 39 degree C base line, the detection latency in the incorrect signal condition was greater than in the unsignaled condition, but the latter latency was not different from the correct signal latency. In addition, the percent of undetected T2s was the same on all three types of trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Serotoninergic axonal contacts on identified cat spinal dorsal horn neurons and their correlation with nucleus raphe magnus stimulation.

This study examined the distribution of serotoninergic (5-HT) immunoreactive axonal contacts on spinal laminae I and II neurons by combining the intracellular horseradish peroxidase (HRP) method with immunocytochemistry. In addition, the 5-HT distribution was correlated with effects produced by electrical stimulation within the nucleus raphe magnus (NRM). Responses of lamina I neurons and lamina II stalked cells to noxious stimulation were markedly suppressed during NRM stimulation. In contrast, responses of nociceptive lamina IIa islet or non-nociceptive lamina IIb islet cells remained unchanged during nucleus raphe magnus stimulation. These inhibitory influences were positively correlated with the distribution of 5-HT immunoreactive contacts on these neurons. Nociceptive lamina I neurons and lamina II stalked cells received a significantly greater number of contacts (average of 74 and 63, respectively) than either nociceptive lamina IIa islet or non-nociceptive lamina IIb islet cells (average of 25 and eight contacts, respectively). Irrespective of cell type, most 5-HT contacts occurred on dendritic shafts rather than spines. These data reveal a differential distribution of 5-HT contacts on neurons in spinal laminae I and II, and indicate that at least a portion of the NRM modulation of dorsal horn neuronal activity is serotoninergic and concentrated on the dendritic shafts of nociceptive lamina I neurons and lamina II stalked cells.

Animals↗

The morphology of dorsal column postsynaptic spinomedullary neurons in the cat.

Dorsal column postsynaptic ( DCPS ) spinomedullary neurons from the cat's lumbosacral enlargement were identified by antidromic stimulation of the cervical dorsal columns and stained intracellularly with horseradish peroxidase. The cell bodies were located in laminae III-IV. Their dendritic arbors were elongated rostrocaudally but narrow mediolaterally. On the average, the arbors were X 5 longer than they were wide. Most of the neurons had nearly all of their dendrites in laminae III-IV and some of the neurons had, in addition, a considerable amount of dendritic surface area in lamina V. Only one neuron had more than a very small amount of dendritic surface area dorsal to lamina III. Seven of the neurons had unmyelinated axon collaterals that arborized extensively and issued varicosity-bearing terminal branches in laminae III-V, both within and beneath their dendritic territories. All of the neurons were excited by myelinated, low-threshold mechanoreceptors. Since the rostrocaudally elongated and mediolaterally narrow dendritic arbors of DCPS neurons are in register with the laminae III-IV terminal distributions of myelinated, low-threshold mechanoreceptors, it is probable that this excitation arises from a monosynaptic and topographically discrete innervation. About one-half of the DCPS neurons were also excited by noxious stimuli. It is probable that this excitation is accomplished by a polysynaptic pathway since DCPS dendritic arbors and nociceptor terminal distributions are largely or completely separate.

Afferent Pathways↗

Activity of trigeminothalamic neurons in medullary dorsal horn of awake monkeys trained in a thermal discrimination task.

We analyzed the activity of 51 trigeminothalamic neurons in the medullary dorsal horn (trigeminal nucleus caudalis) of monkeys during the performance of behavioral tasks requiring the monkeys to discriminate innocuous and noxious thermal stimuli applied to the face and to detect the onset of visual stimuli. Static properties of trigeminothalamic neurons in behaving monkeys were similar to those in anesthetized monkeys. Responses to passively presented mechanical and thermal stimuli, receptive-field properties, and conduction velocities did not differ in the awake and anesthetized states. For most wide dynamic range and nociceptive-specific trigeminothalamic neurons, there was a negative correlation between the magnitude of thermally evoked activity and behavioral latencies to discriminate 47 and 49 degrees C stimuli. Thus, both groups of neurons provide information that could be used by the monkey to discriminate noxious thermal stimuli. The magnitude of thermal responses of trigeminothalamic neurons was modulated by the behavioral significance of the stimulus. Behaviorally relevant thermal stimuli presented during the thermal discrimination task produced a greater neuronal response than equivalent irrelevant thermal stimuli presented between behavioral trials or presented while the monkey performed the visual detection task. Neurons whose activity is modulated by behavioral state are likely to be involved in discrimination of thermal stimuli, since the activity of these neurons correlates with the behavioral response to the stimuli and information from the modulated neurons is sent to the thalamus. Some trigeminothalamic neurons that exhibited somatosensory responses also responded to behaviorally relevant stimuli and events associated with trial initiation and receipt of reward in the behavioral tasks. Similar events outside a behavioral task evoked no neuronal responses. These task-related responses were similar to those described previously for medullary dorsal horn neurons not identified as to projection sites (14).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Nitrous oxide analgesia: a psychophysical evaluation using verbal descriptor scaling.

The effect of 33% nitrous oxide/67% oxygen was compared with 100% oxygen and air on verbal reports of either sensory intensity or unpleasantness of sensations associated with painful electrical tooth pulp stimulation. Forty-eight subjects used words describing the sensory intensity (i.e., weak, mild, strong) or degree of unpleasantness (i.e., annoying, unpleasant, distressing) to assess the sensations produced by a broad range of tooth pulp stimuli. Within the experimental session, a given subject assessed the painful sensations under all three treatments delivered through a nasal inhaler in a double-blind manner. The incorporation of within-subject placebo (nasal inhaler + air) and active placebo (nasal inhaler + oxygen) controls allowed for rigorous assessment of the components of nitrous oxide analgesia. The results of this study suggest that 33% nitrous oxide analgesia reduces the intensity but not the unpleasantness of painful tooth pulp sensations. Further, 100% oxygen provides no analgesic effect.

Anesthesia, Dental↗

Suppression of postoperative pain by the combination of a nonsteroidal anti-inflammatory drug, flurbiprofen, and a long-acting local anesthetic, etidocaine.

The analgesic efficacy of the combination of a nonsteroidal anti-inflammatory drug, flurbiprofen, and a long-acting local anesthetic, etidocaine, was evaluated for the suppression of acute postoperative pain. Subjects having two impacted third molars removed at two appointments received either the experimental combination or standard treatment in a randomized, crossover design. The experimental treatment consisted of 100 mg flurbiprofen 30 minutes before surgery, 1.5% etidocaine with 1:200,000 epinephrine five minutes before surgery, and 100 mg flurbiprofen three hours after surgery. Standard treatment consisted of 10 mg oxycodone plus 650 mg acetaminophen 30 minutes before surgery, 2% lidocaine with 1:100,000 epinephrine five minutes before surgery, and a second dose of the oxycodone-acetaminophen combination three hours after surgery. Pain intensity was rated hourly from one to seven hours after surgery, using a variety of ordinal and analog scales. The flurbiprofen-etidocaine combination resulted in significantly less postoperative pain than the oxycodone plus acetaminophen-lidocaine combination on all four analgesic scales used and was preferred by the majority of the patients. This study shows that pretreatment with a nonsteroidal anti-inflammatory drug, flurbiprofen, in combination with a long-acting local analgesic, etidocaine, suppresses pain to a greater extent than a potent opiate mild/analgesic combination and lidocaine without an increase in side-effect liability.

Acetanilides↗

Demonstration of postsynaptic opioid modulation of thalamic projection neurons by the combined techniques of retrograde horseradish peroxidase and enkephalin immunocytochemistry.

Thalamic projection neurons represent a major source of nociceptive information from the dorsal horn to higher centers of the neuraxis. The synaptic relationship between thalamic projection neurons and the opioid peptide enkephalin (ENK) was examined at the light (LM) and ultrastructural (EM) level using the combined techniques of retrograde transport of horseradish peroxidase and ENK immunocytochemistry. Utilizing two different chromogens to develop the peroxidase reaction product, the two labeled neural elements could be readily distinguished at the LM level in the same tissue section. In the medullary, cervical, and lumbar levels of the dorsal horn of both the cat and monkey, at least 30% of the thalamic projection neurons in lamina I were observed at the LM level to be contacted by ENK-immunoreactive varicosities. In lamina V, approximately 50% of the thalamic projection neurons received ENK contacts. Since some neurons were not observed to receive a dense ENK innervation on their somata and proximal dendrites, these data suggest that there may be different functional types of thalamic projection neurons. At the EM level, the ENK-immunoreactive varicosities were observed to form asymmetrical synaptic contacts on the labeled somata and proximal dendrites of the projection neurons. In all cases, the ENK varicosities were morphologically similar and contained round or oval agranular vesicles and a few dense-core vesicles. These observations suggest that ENK acts to a substantial degree on postsynaptic opiate receptors located on thalamic projection neurons.

Afferent Pathways↗

Immunocytochemical identification of serotonin axonal contacts on characterized neurons in laminae I and II of the cat dorsal horn.

Serotonergic pathways from brainstem to spinal cord play an important role in the modulation of pain perception. To establish where that modulation occurs, we examined serotonin-immunoreactive axonal contacts on individually characterized laminae I and II dorsal horn neurons intracellularly filled with horseradish peroxidase. We found serotonin axonal contacts on marginal, stalked, and islet cells. Contacts preferentially occurred on dendritic shafts rather than on spines. Marginal and stalked cells received the heaviest innervation.

Animals↗

Extra- and intracellular recordings from dorsal column postsynaptic spinomedullary neurons in the cat.

Dorsal column postsynaptic (DCPS) spinomedullary neurons in the dorsal horn of spinal segments L6-S1 of adult cats anesthetized with sodium pentobarbital were identified by antidromic stimulation of cervical dorsal columns that were dissected free of, and electrically isolated from, the rest of the spinal cord. The neurons were categorized with respect to natural stimulation of their cutaneous receptive fields. An equal number of low-threshold mechanoreceptive and wide-dynamic-range neurons were found. No DCPS neurons could be classified as nociceptive-specific. All neurons received input from low-threshold mechanoreceptors with myelinated axons. There was no evidence that any neurons received monosynaptic input from unmyelinated, primary afferent fibers. The average conduction velocity of the antidromic responses was 45.7 m/s. Nearly half of the DCPS cells showed an antidromic spike followed by synaptically driven responses that were probably evoked by antidromic invasion into the intraspinal collaterals of A-beta primary afferent fibers that ascended the dorsal columns. Intracellularly recorded synaptic responses of DCPS neurons to dorsal column and receptive field stimulation usually consisted of an EPSP with overriding spike potentials followed by a prolonged IPSP whose amplitude decreased markedly as the stimulus frequency was increased in the range of 5 to 30 Hz. The results indicate that DCPS neurons constitute a projection system capable of signaling innocuous and tissue-damaging mechanical stimuli. The DCPS projection may play a role in the modulation of touch and pain perception.

Animals↗

Non-pain and pain sensations evoked by tooth pulp stimulation.

This study investigated the quality and magnitude of sensations evoked by electrical tooth pulp stimulation. Detection threshold (the minimum current intensity that evoked a sensation) and pain threshold were determined for tooth pulp stimuli varying in frequency from 5 to 500 Hz. The effect of frequency and intensity of tooth pulp stimulation on the magnitude of sensations was assessed using visual analog scales and verbal descriptor scales. Detection thresholds were stable over experimental sessions and independent of the frequency of the stimulating current. Pain threshold varied as a function of frequency with a minimum value at 100 Hz. Stimuli that evoked non-pain sensations at low frequencies evoked pain sensations when frequency was increased from 5 to 100 Hz. Subjects were able to scale non-pain sensations over a range of stimulus intensities and frequencies. The lowest currents evoked sensations that were non-painful and were of constant magnitude despite changes in the frequency of stimulation. Higher stimulus currents evoked sensations that were non-painful at low stimulus frequencies and painful at high stimulus frequencies. Sensation magnitude at each stimulus intensity increased as a function of frequency. Temporal summation occurred in proportion to stimulus intensity. These findings suggest that the non-pain sensations evoked in tooth pulp are mediated by a distinct population of afferents that are not involved in the coding of pain. High frequency stimulation that increased the discharge rate of the lowest threshold pulpal afferents resulted in no summation of non-pain sensation and never produced pain. However, high frequency stimulation evoked greater magnitude sensations at higher stimulus currents, indicating that central summation mechanisms were critical for higher threshold afferents signaling more intense non-pain and pain sensations.

Adolescent↗

Immunocytochemical evidence for a serotoninergic innervation of dorsal column postsynaptic neurons in cat and monkey: light- and electron-microscopic observations.

Dorsal column postsynaptic neurons in the lumbosacral enlargements of cats and a monkey were retrogradely labeled by placing horseradish peroxidase on their severed axons in the thoracic dorsal columns. After visualizing the retrogradely-labeled neurons, the tissue was immunocytochemically stained with an antiserum directed against serotonin. Immunoreactive axonal varicosities contacted the perikarya and proximal dendrites of every retrogradely-labeled neuron examined in cat (mean 61 contacts/cell) and nearly every neuron in the monkey (mean 18 contacts/cell). Electron microscopy showed that the immunoreactive axonal varicosities contained pleomorphic (round to oval) agranular vesicles and formed symmetrical synapses on retrogradely-labeled neurons. It is concluded that dorsal column postsynaptic neurons are innervated directly by the brain stem's descending, serotoninergic system(s).

Animals↗

Discrimination of innocuous and noxious thermal stimuli applied to the face in human and monkey.

Four humans and one monkey performed two-choice discriminations between simultaneous 3-sec heat stimuli applied to the face. All subjects produced more accurate discriminations in the noxious thermal range (approximately 47 degrees C) than in the innocuous thermal range (approximately 39 degrees C). The difference threshold, defined as the smallest temperature difference detected on 75% of the trials, was smaller for every subject at 47 degrees C than at 39 degrees C. The monkey's discriminative performance was comparable to that of humans in the noxious range, but inferior to that of humans in the innocuous range. Subjects' superior discrimination at noxious temperatures cannot be easily accounted for by differences in primary afferent activity of warm fibers and heat-nociceptive fibers. However, differences in central processing or attentional modulation could contribute to superior discrimination in the noxious range. These findings indicate that heat-sensitive nociceptors are capable of transmitting precise information about noxious thermal input to the skin.

Animals↗

The cells of origin of the dorsal column postsynaptic projection in the lumbosacral enlargements of cats and monkeys.

Dorsal column postsynaptic (DCPS) neurons in the lumbosacral enlargements of cats and macaque monkeys were retrogradely labeled by placing HRP on their severed axons within the dorsal columns. The enlargements of both species contained 800-1,100 labeled DCPS neurons. The DCPS projection is thus as large as the feline spinocervical tract. It is very probable that most of these neurons project to the dorsal column nuclei and thereby constitute one of the major sources of somatosensory input to the brain. In the cat, DCPS neurons were concentrated in a band centered in lamina IV that swept down through laminae V-VI along the medial border of the dorsal horn. A second concentration of labeled cells was found in dorsomedial lamina VII. In the monkey, DCPS neurons were concentrated in a relatively broader band in laminae III-IV, and scattered cells were consistently observed throughout laminae V-VII and X and in the dorsolateral white matter. The prominence of the monkey's DCPS projection suggests that humans also have such a projection.

Animals↗

Enkephalin immunoreactive stalked cells and lamina IIb islet cells in cat substantia gelatinosa.

Neurons in lamina II of the lumbar spinal cords of colchicine-pretreated cats were stained immunocytochemically for enkephalin. Two morphological types were found. The most common type had the light microscopic characteristics of stalked cell. The other type was found in the deep part of the lamina and had the light and electron microscopic characteristics of the lamina IIb islet cell.

Animals↗

Masseter inhibitory periods and sensations evoked by electrical tooth pulp stimulation in patients with oral-facial pain and mandibular dysfunction.

The masseter inhibitory period (silent period) and sensations evoked by tooth-pulp stimulation were examined in 12 healthy subjects and 12 patients with oral-facial pain and mandibular dysfunction (MPD). Trains of 30 pulses were applied to an upper incisor and the threshold intensities for detecting sensation, for detecting pain sensation and for the masseter inhibitory period were determined. Masseter activity was monitored during tooth stimulation by electromyographic recordings from surface electrodes. Electrical tooth stimulation elicited three different configurations of masseter inhibitory periods in both groups: single, double and merged. MPD patients exhibited a greater proportion of single inhibitory periods. The combined average total durations of the three types of configurations were less in MPD. The findings are consistent with the hypothesis that there is an increase in excitability of the central masseter motorneuron pool in MPD, resulting in a reduction in the effective duration of the masseter inhibitory period. The higher incidence of single inhibitory periods in MPD patients also could result from this increased central excitatory state. There was no difference between masseter inhibitory periods evoked in either painful or non-painful muscles, and no particular configuration associated with pain sensation. The findings do not support the hypothesis that nociceptive input contributes to the increase in duration of the silent period in MPD. Although there were no significant differences between masseter inhibitory period threshold, detection thresholds or pain threshold for both groups, MPD patients had detection thresholds higher than their masseter inhibitory thresholds. These effects may be related to differential central neural influences on sensory-discriminative and reflex pathways in the trigeminal system.

Adolescent↗