Search PubMed⌕ Search

Biomedical subjects

R Dubner

Publications and source records attributed to R Dubner.

At least 73 records · Page 4Linked to original sources
PubMed1989

Corticotropin releasing factor (CRF) has a peripheral site of action for antinociception.

In the rat carrageenan model of inflammation, systemically administered CRF significantly reduced hyperalgesia, edema and hyperthermia. While hypophysectomy had no effect, adrenalectomy blocked the effects of systemic CRF on edema and hyperthermia, and tended to reduce the peptide's ability to suppress hyperalgesia. When CRF was injected into one of two bilaterally inflamed hindpaws, it significantly inhibited hyperalgesia via a peripheral mechanism. In this model of inflammation, the antinociceptive effects of CRF are peripherally mediated, while the anti-inflammatory effects are dependent on the adrenal gland.

Adrenalectomy↗
PubMed1989

Peripheral inflammation is associated with increased dynorphin immunoreactivity in both projection and local circuit neurons in the superficial dorsal horn of the rat lumbar spinal cord.

The present study combined the retrograde transport of fluorescent tracers with the immunocytochemical identification of dynorphin A(1-8) in superficial dorsal horn neurons to examine whether peripheral inflammation-induced dynorphin increases are found in local circuit neurons only or also in neurons projecting at least to the caudal mesencephalon. Evidence is presented that complete Freund's adjuvant-induced inflammation produces a large increase in the number of lamina I dynorphin-containing projection and non-projection neurons, and in the number of lamina II dynorphin local circuit neurons.

Animals↗
PubMed1989

The neurobiology of pain and its modulation.

Recent research advances indicate that specialized neural pathways are involved in the encoding of pain sensations and that these pathways are sensitive to changes in stimulus features, such as intensity, quality, duration, and location. It has also been established that there are three major families of opioid peptides in the brain: the enkephalins, the dynorphins, and the endorphins. In addition to these opioid peptides, other neurochemicals such as serotonin and norepinephrine play a role in the modulation of signals related to tissue damage. These advances in research are being used to develop improved methods for the control of acute and chronic pain. Nonsteroidal anti-inflammatory drugs suppress noxious signals by reducing the sensitization of peripheral nociceptors. Opioid drugs are administered into the membranes surrounding the spinal cord to provide long-lasting pain relief. Peripherally acting opioid drugs may represent a new functional class of analgesics devoid of the undesirable side effects of centrally acting opioids. Tricyclic antidepressant drugs are used in the treatment of neuropathic pain, based on their effects on noradrenergic and serotoninergic pathways in the central nervous system.

Animals↗
PubMed1989

The detection and perceived intensity of noxious thermal stimuli in monkey and in human.

1. The magnitude of the sensations produced by small increases in thermal stimuli superimposed on noxious levels of heat stimulation was studied by the use of a simple reaction-time task. Noxious thermal stimuli were presented on the face of three monkeys, the forearm volar surface of three monkeys, and the face of four human subjects. The subject, either monkey or human, initiated a trial by pressing an illuminated button. Subsequently, a contact thermode increased in temperature from a base line of 38 degree C to temperatures of 44, 45, 46, or 47 degrees C (T1). After a variable time period lasting between 4 and 10 s, the thermode temperature increased an additional 0.1, 0.2, 0.4, 0.6, or 0.8 degrees C (T2). The subject was required to release the button as soon as the T2 stimulus was detected. Detection latency, expressed as its reciprocal, detection speed, was defined as the time interval between the onset of T2 and the release of the button. 2. The monkeys' detection speed to stimuli presented on the upper lip was dependent on the intensity of both T1 and T2. Increases in the intensity of T2 between 0.1 and 0.8 degrees C produced faster detection speeds. In general, as the intensity of T1 increased, the detection speed increased to identical T2 stimuli. The monkeys' T2-detection threshold was also dependent on the intensity of T1. 3. The psychophysical functions obtained from stimulation of the monkey's face were compared with those obtained from the volar surface of the monkey's forearm. Whereas the T2 thresholds obtained from stimulation of the monkey's forearm and face were similar, the psychophysical functions obtained from stimulation of the face were significantly steeper than those obtained from stimulation of the forearm. 4. The humans' detection speed of T2 stimuli presented on the face was monotonically related to the intensity of T2 and was dependent on the level of T1. The psychophysical functions obtained from the human's face were equivalent to those obtained from the monkey's faces. 5. A cross-modality matching procedure was used to examine the perceived intensity of pain sensation produced by T2 stimuli in human subjects. The magnitude estimates of these stimuli were dependent on the level of T1, as well as the intensity of T2. Detection speed, plotted as a function of the estimated magnitude of pain, independent of T1 and T2 temperature, was best fit by a logarithmic function.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Responses of monkey medullary dorsal horn neurons during the detection of noxious heat stimuli.

1. We examined the activity of thermally sensitive trigeminothalamic neurons and nonprojection neurons in the medullary dorsal horn (trigeminal nucleus caudalis) in three monkeys performing thermal and visual detection tasks. 2. An examination of neuronal stimulus-response functions, obtained during thermal-detection tasks in which noxious heat stimuli were applied to the face, indicated that wide-dynamic-range neurons (WDR, responsive to innocuous mechanical stimuli with greater responses to noxious mechanical stimuli) could be subclassified based on the slope values of linear regression lines. WDR1 neurons exhibited significantly greater sensitivity to noxious heat stimulation than WDR2 neurons or nociceptive-specific neurons (NS, responsive only to noxious stimuli). 3. In one behavioral task, the monkeys detected 1.0 degrees C increases in noxious heat from preceding noxious heat stimuli ranging from 44 to 48 degrees C. WDR1, WDR2, and NS neurons increased their discharge frequency as a function of the intensity of the first noxious heat temperature (T1) as well as the final temperature (T2). The responses of WDR1 neurons were greater than those produced by WDR2 or NS neurons across all the temperatures examined. The order of stimulus presentation affected the responses of WDR1 neurons to 1.0 degrees C increases in the noxious heat range but not those of WDR2 or NS neurons. 4. In a second behavioral task, the monkeys detected small increases in noxious heat (0.2-0.8 degrees C) from a first temperature of 46 degrees C. Although the responses of all three classes of neurons were monotonically related to stimulus intensity, WDR1 neurons exhibited greater sensitivity to small temperature increases than either WDR2 or NS neurons. 5. Subpopulations of all three classes of neurons exhibited responses that were independent of thermal stimulus parameters or sensory modality and that only occurred during the behavioral task. These task-related responses were time-locked to specific behavioral events associated with trial initiation and trial continuation. 6. These data provide evidence that a subpopulation of WDR neurons is the dorsal horn cell type most sensitive to small increases in noxious heat in the 45-49 degrees C temperature range and provides the most information about stimulus intensity. The findings support the view that nociceptive neurons have the capacity to precisely encode stimulus features in the noxious range and that WDR neurons are likely to participate in the monkeys' ability to perceive the intensity of such stimuli.

Afferent Pathways↗
PubMed1989

The correlation of monkey medullary dorsal horn neuronal activity and the perceived intensity of noxious heat stimuli.

1. We examined the relationship between the activity of medullary dorsal horn nociceptive neurons and the monkeys' ability to detect noxious heat stimuli. In two different detection tasks, the temperature of a contact thermode positioned on the monkey's face increased from 38 degrees C to temperatures between 44 and 48 degrees C (T1). After a variable time period, the thermode temperature increased an additional 0.2-1.5 degrees C (T2), and the monkeys' detection speed from the onset of T2 was determined. We previously have established that detection speed is a measure of the perceived intensity of noxious thermal stimuli. Nociceptive neurons were classified as wide-dynamic-range (WDR, responsive to innocuous mechanical stimuli with greater responses to noxious mechanical stimuli) and nociceptive-specific (NS, responsive only to noxious stimuli). WDR neurons were subclassified as WDR1 and WDR2 based on the higher slope values of the stimulus-response functions of WDR1 neurons. The monkeys were trained to detect small increases in noxious heat, and their detection speeds were correlated with the responses of WDR1, WDR2, and NS neurons. 2. Detection speeds to T2 temperatures of 1.0 degrees C from preceding T1 temperatures of 45 and 46 degrees C were faster during a preceding ascending series of stimuli than during a descending series. Similarly, the peak discharge frequencies of WDR1 neurons in response to the same stimuli were greater during the ascending series of T2 temperatures. In contrast, the responses of WDR2 and NS neurons showed no significant differences during the ascending and descending series of stimuli. 3. Detection speeds following 0.4, 0.6, and 0.8 degrees C T2 stimuli were higher when the preceding T1 temperature was 46 degrees C as compared with detection speeds to the identical stimuli when the preceding T1 temperature was 45 degrees C. WDR1 neurons also exhibited a significant increase in peak discharge frequency to these same T2 stimuli when the preceding T1 temperature was 46 degrees C. In contrast, the neuronal activity of WDR2 and NS neurons did not differ on 45 and 46 degrees C T1 trials. 4. The relationship between detection speed and neuronal peak discharge frequency was examined in response to different pairs of T1 and T2 stimuli when T1 was either 45 or 46 degrees C. There was a significant correlation between detection speed and neuronal discharge for WDR1 and WDR2 neurons. No correlation was observed for NS neurons. 5. The magnitude of neuronal activity on correctly detected and nondetected trials was compared when T1 was 46 degrees C and T2 was 0.2 degree C.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Advances in the epidemiological study of oral-facial diseases.

Both demographic patterns and disease distribution are changing rapidly in the United States. These developments have led to the recognition that the epidemiology of many conditions is poorly understood, and that other research has thus been hindered. Four areas of epidemiological study were chosen for detailed analysis of how new technology will affect the conduct of future research. These areas, selected because information about them will be increasingly needed in an aging society, were periodontitis, temporomandibular disorders (TMD) and other orofacial pain, salivary gland disturbances, and health services research. The potential effect of new technology was examined in the short, intermediate, and long term. While the nature of epidemiological study is unlikely to change with the advent of new technology, the scope of potential studies will become broader. Advances in diagnostic techniques from elsewhere will permit far more precise diagnosis than is possible at present. Computer technology will permit an efficient system of epidemiological surveillance to provide current data on trends in tooth loss, caries, and periodontitis--data which will complement the results of national surveys. Analytical studies to produce hypotheses on the etiology of oral conditions, especially in such poorly-understood areas as chronic pain and TMD, will help direct clinical research in those areas.

Computers↗
PubMed1989

Advances in diagnosis and detection of oral diseases.

Medicine, particularly with respect to diagnostic decision-making, has seen remarkable advances in the last ten years. The art of diagnosis has become much more of a science. Basic science advances have moved from the laboratory into the hospital and radically changed the way a medical diagnosis is arrived at or confirmed. Dentistry, especially oral diagnosis, as yet has not been a significant part of this general medical advance. However, several examples demonstrate that this situation is starting to change. Oral conditions are beginning to be evaluated with greater precision and sophistication. This report reviews some recent advances in oral diagnostic research and suggests where they will carry dentistry over the next 25 years.

Diagnosis, Oral↗
PubMed1988

SI nociceptive neurons participate in the encoding process by which monkeys perceive the intensity of noxious thermal stimulation.

The activity of primary somatosensory (SI) cortical nociceptive neurons was recorded while the monkeys performed a psychophysical task in which they detected small increases in skin temperature superimposed on noxious levels of thermal stimulation. The detection latency to these stimuli, expressed as detection speed, was used as a measure of the perceived intensity of sensation. Two-thirds of the neurons that responded to noxious thermal stimulation increased their discharge in response to graded increases in stimulus intensity. The remaining neurons responded to noxious thermal stimulation, but did not grade their response with the intensity of the stimulus. The response of SI nociceptive neurons that encode the intensity of noxious thermal stimulation was significantly correlated with the monkey's detection speed. We conclude that SI nociceptive neurons are involved in the encoding process by which monkeys perceive the intensity of noxious thermal stimulation.

Afferent Pathways↗
PubMed1988

Centrifugal activity in afferent C-fibers influences the spontaneous afferent barrage generated in nerve-end neuromas.

We have investigated the effect of a prolonged, low-frequency impulse barrage on the spontaneous afferent discharge that originates in experimental nerve-end neuromas in the rat sciatic nerve. Centrifugal activity in afferent A-fibers did not affect electrogenesis in the neuroma. When C-fibers were recruited, however, over half of the axons tested were either suppressed or excited. We suggest that these effects resulted from the stimulation-evoked release of neuroactive peptides or related substances from the cut ends of afferent C-fibers.

Afferent Pathways↗
PubMed1988

A multiple random staircase method of psychophysical pain assessment.

Three experiments evaluated the reliability and sensitivity of an interactive multiple random staircase (MRS) assessment of painful thermocutaneous sensations. One hundred and sixteen subjects used a 4-point category scale (no pain, mild, moderate, intense) to rate the intensity of sensations produced by 3-sec thermal stimuli applied to the volar forearm at 20-sec intervals by a 1-cm diameter contact thermode. Each of the 3 intervals between the 4 verbal responses was defined as a boundary. A pair of staircases was associated with each boundary. On each trial, 1 of the 6 staircases was chosen randomly and the stimulus intensity indicated by that staircase presented. The response to that stimulus determined the intensity presented by that staircase the next time it was randomly selected. Responses above the associated boundary decreased stimulus intensity, responses below the associated boundary increased stimulus intensity. In the first experiment, 1 staircase from each of the 3 boundaries began at 43 degrees C and 1 began at 48 degrees C. Staircases for each boundary converged to within 0.3 degree C after 12 trials/staircase. The sensitivity of the method to a narcotic analgesic was assessed by open (exp. II) and double-blind (exp. III) intravenous infusion of 1.1 micrograms/kg fentanyl. Administration of fentanyl increased staircase temperatures, indicating that these higher temperatures were now required to elicit the same verbal responses. This shift in temperature reached a peak effect 11 min after fentanyl administration. These results suggest that this method provides a reliable measure of sensory magnitude in units of stimulus intensity. It does not require assumptions about psychological units of pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-Blind Method↗
PubMed1988

A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia.

A method to measure cutaneous hyperalgesia to thermal stimulation in unrestrained animals is described. The testing paradigm uses an automated detection of the behavioral end-point; repeated testing does not contribute to the development of the observed hyperalgesia. Carrageenan-induced inflammation resulted in significantly shorter paw withdrawal latencies as compared to saline-treated paws and these latency changes corresponded to a decreased thermal nociceptive threshold. Both the thermal method and the Randall-Selitto mechanical method detected dose-related hyperalgesia and its blockade by either morphine or indomethacin. However, the thermal method showed greater bioassay sensitivity and allowed for the measurement of other behavioral parameters in addition to the nociceptive threshold.

Animals↗
PubMed1988

Association of pain relief with drug side effects in postherpetic neuralgia: a single-dose study of clonidine, codeine, ibuprofen, and placebo.

In a randomized, double-blind crossover study, 40 patients with postherpetic neuralgia were given single oral doses of clonidine, 0.2 mg, codeine, 120 mg, ibuprofen, 800 mg, or inert placebo. Pain relief and side effects were recorded for 6 hours. Patients reported significantly more relief after clonidine than after the other three treatments. Codeine and ibuprofen were ineffective. Sedation, dizziness, and other side effects were more frequent after clonidine (74%) or codeine (69%) than after placebo (36%) or ibuprofen (28%). Reported pain relief was greater during trials in which side effects were present. A single, mild side effect was associated with as much additional pain relief as multiple, severe side effects. Clonidine's superiority to codeine, which had a similar incidence of side effects, argues for a specific analgesic effect. In addition, side effects may have contributed to clonidine analgesia, perhaps by suggesting to patients that they had received a potent drug.

Aged↗
PubMed1988

Amitriptyline, but not lorazepam, relieves postherpetic neuralgia.

In a double-blind, randomized, crossover study, 58 patients with postherpetic neuralgia received 6-week courses of amitriptyline, 12.5 to 150 mg/d; lorazepam, 0.5 to 6 mg/d; or lactose placebo. Doses were titrated to the maximum level tolerated. Patients rated pain in a diary, using lists of verbal descriptors. Forty-seven percent of patients reported moderate or greater relief with amitriptyline, 16% with placebo, and 15% with lorazepam. Mean amitriptyline dose was 65 mg/d. Greater relief was associated with higher amitriptyline doses, up to the maximum dose of 150 mg/d, and with higher serum tricyclic levels. Lorazepam did not relieve pain and was associated with severe depressive reactions in four patients.

Adult↗
PubMed1987

Corticotropin-releasing factor (CRF) produces analgesia in humans and rats.

The analgesic activity of corticotropin releasing factor (CRF) was determined in a clinical model and in the rat hot plate test. Patients administered CRF reported significantly less postoperative pain than patients pretreated with placebo. In rats, injection of CRF resulted in a significant analgesia which was comparable in both intensity and duration to a 300 times greater molar dose of morphine. These findings suggest that endogenous CRF may play a physiologic role in modulating pain when released under conditions of stress.

Analgesia↗
PubMed1987

Altered responses of nociceptive cat lamina I spinal dorsal horn neurons after chronic sciatic neuroma formation.

The activity of lumbar spinal dorsal horn lamina I neurons with afferent drive from the sciatic nerve was studied in intact cats and in cats with acute sciatic nerve transection or chronic sciatic nerve transection with neuroma formation. The majority (51 of 75) of neurons recorded in lamina I ipsilateral to a neuroma had no receptive field and could only be identified by their responses to electrical stimulation of the sciatic nerve. The remainder could be activated by the sciatic nerve, but their responses to mechanical stimulation were irregular in comparison to the stable responses of cells recorded in control animals and to the responses of cells contralateral to chronic nerve lesions. Animals with acute nerve transections demonstrated a loss of sciatic nerve-innervated cells with receptive fields except for those cells located on the lateral edge of the dorsal horn, which had normal, proximal receptive fields and response characteristics. In addition, the characteristic somatotopy of lamina I cells was not observed in some cats with chronic neuromata. The mediolateral distribution of cell types indicated that some cells had altered receptive fields following chronic nerve transection. The data presented for lamina I neurons agrees with the observation of spinal cord plasticity first presented for cat dorsal horn cells. Since there is no evidence for a redistribution of intact afferent fibers following chronic nerve transection in adult mammals, the mechanism of altered somatotopy may involve alterations in synaptic efficacy at existing synapses.

Afferent Pathways↗