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Biomedical subjects

R Dubner

Publications and source records attributed to R Dubner.

At least 91 records · Page 5Linked to original sources
PubMed1987

Idiopathic trigeminal neuralgia: sensory features and pain mechanisms.

We present a case report of a patient with the typical sensory features of idiopathic trigeminal neuralgia (ITN). The pain was elicited by innocuous stimuli, summated with repeated stimulation, radiated outside the stimulus zone, referred to a distant site, persisted beyond the period of stimulation, and exhibited a variable refractory period. Unusual sensory features included multiple trigger zones that changed over time and involved all 3 trigeminal divisions. Our sensory evaluation indicated that the pain was evoked by repetitive activation of rapidly adapting, A beta, low-threshold mechanoreceptive afferents. However, activation of such mechanoreceptive afferents alone never produces pain in normal situations and often leads to a suppression of pain responsivity. The findings support the idea that the mechanism of pain in ITN involves pathophysiological mechanisms in the central nervous system. Our hypothesis is that structural and functional changes in the trigeminal system result in an alteration in the receptive field organization of wide-dynamic-range (WDR) neurons. There appears to be an alteration in the surround inhibition mechanism of these neurons leading to an expansion of their touch receptive fields. This results in touch stimuli producing activity in WDR neurons that mimics the activity produced under normal conditions by noxious stimuli. Since WDR neurons participate in the encoding of the perceived intensity of noxious stimuli, a series of punctate tactile stimuli are now perceived as localized, pin-prick or electric shock-like sensations. Similar pathophysiological mechanisms may explain, in part, the pain of peripheral neuropathies associated with postherpetic neuralgia, diabetes and causalgia.

Electric Stimulation↗
PubMed1987

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↗
PubMed1987

Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood.

In a randomized, double-blind crossover study, 29 patients with painful diabetic neuropathy received 6 weeks of amitriptyline and 6 weeks of an "active" placebo that mimicked amitriptyline side effects. Amitriptyline was superior to placebo in relieving pain in weeks 3 through 6. Both steady, burning pain and lancinating pains were relieved. Patients able to tolerate higher amitriptyline doses reported greater relief, through the maximum dose of 150 mg nightly. Amitriptyline analgesia was similar in depressed and nondepressed subgroups and was not associated with mood improvement. We conclude that amitriptyline relieves pain in diabetic neuropathy; this effect is independent of mood elevation.

Adult↗
PubMed1987

Opioid analgesia at peripheral sites: a target for opioids released during stress and inflammation?

The peripheral analgesic effects of opiates were evaluated in a rat model of inflammation. The experimental design excluded a potential central nervous system site of action for the observed analgesia. After the injection of carrageenan (CARRA) in the plantar surface of both hind paws, an opiate was injected into one paw and saline was injected into the other paw. The inflamed paws injected with the mu-agonist, fentanyl (0.3 micrograms) or the kappa-agonist, ethylketocyclazocine (10 micrograms) were significantly less hyperalgesic (P less than 0.001 and P less than 0.01, respectively) than were the contralateral inflamed paws injected with saline. At these doses, fentanyl and ethylketocyclazocine were devoid of systemic effects. Another mu-agonist, levorphanol (20, 40, 80, or 160 micrograms) and dextrorphan (160 micrograms), its dextrorotatory isomer, were used next to evaluate opioid specificity. Levorphanol produced a dose-related blockade of CARRA-induced hyperalgesia (P less than 0.005). In contrast, 160 micrograms of dextrorphan was inactive. These results demonstrate that local administration of opiates into an inflamed paw produces a dose-related, stereospecific analgesia restricted to the injected area.

Analgesics, Opioid↗
PubMed1986

Wide-dynamic-range dorsal horn neurons participate in the encoding process by which monkeys perceive the intensity of noxious heat stimuli.

The role of dorsal horn wide-dynamic-range (WDR) and nociceptive-specific (NS) neurons in the encoding of the perceived intensity of noxious stimuli was determined while monkeys detected near-threshold changes in the intensity of noxious heat stimuli. Behavioral detection latencies were a reliable measure of the perceived intensity of these stimuli. There was a significant correlation between behavioral detection latency and neuronal discharge of WDR, but not NS neurons. In addition, WDR neurons exhibited greater activity on correctly detected vs non-detected trials, whereas NS neurons did not. We conclude that WDR neurons are involved in the encoding process by which monkeys perceive the intensity of noxious heat stimuli near detection threshold.

Animals↗
PubMed1986

Physiology and morphology of the lamina I spinomesencephalic projection.

We have examined the physiological and morphological characteristics of spinal dorsal horn lamina I neurons with projections to the midbrain in the cat by combining physiological recording of neurons with the intracellular injection of HRP. Lamina I spinomesencephalic neurons were antidromically activated from the region that included the cuneiform nucleus and lateral periaqueductal gray at the intercollicular level. The majority of mesencephalic projection neurons (50 of 55) responded exclusively to noxious stimulation (nociceptive-specific) of their peripheral receptive fields. Lamina I spinomesencephalic neurons were activated from both the ipsilateral and contralateral midbrain and had slow antidromic conduction velocities (1 to 18 m/second). We identified eight cells with projections to both the midbrain and the thalamus and eight cells that were antidromically activated only from the thalamus. Intracellular injection of HRP revealed that lamina I spinomesencephalic neurons were of diverse morphological types, but generally had extensive, rostrocaudally oriented, dendritic arbors confined to lamina I and the overlying white matter. Axons were observed on nine of the HRP-filled spinomesencephalic neurons; five of the axons issued collateral branches. The morphological characteristics of these neurons did not appear to correlate with functional categories (i.e., wide-dynamic-range- or nociceptive-specific-type neurons). The large number of nociceptive-specific neurons with projections to the midbrain and the interconnections of these midbrain sites with hypothalamic and limbic structures suggest that the lamina I spinomesencephalic pathway plays an important role in the autonomic and affective responses to pain.

Afferent Pathways↗
PubMed1986

Dorsal horn opiate administration attenuates the perceived intensity of noxious heat stimulation in behaving monkey.

In monkeys trained to detect and discriminate noxious heat stimuli, morphine microinjected into the medullary dorsal horn attenuated the perceived intensity of noxious heat in a dose- and stimulus-dependent fashion. These data demonstrate a pharmacologically specific effect of opiates on the sensory intensity component of pain at the earliest central relay pathway transmitting noxious information.

Animals↗
PubMed1986

Serotonin innervation of physiologically identified lamina I projection neurons.

Physiologically characterized lamina I projection neurons, including antidromically activated spinomesencephalic and spinothalamic tract cells, were intracellularly stained with HRP and then processed and examined for serotonin-immunoreactive contacts. We observed cells with both high and low densities of contacts from serotonergic axons. Serotonin contacts were found on both nociceptive-specific and wide-dynamic-range projection neurons. The density of contacts did not appear to correlate with any physiological characteristic.

Animals↗
PubMed1986

Naloxone, fentanyl, and diazepam modify plasma beta-endorphin levels during surgery.

Forty-eight patients received either naloxone (10 mg), fentanyl (0.1 mg), diazepam (0.3 mg/kg), or saline solution placebo, and then underwent surgical removal of impacted third molars under local anesthesia. Placebo resulted in significantly elevated levels of immunoreactive beta-endorphin (i beta-END), norepinephrine, and anxiety during surgery. Patients receiving naloxone had significantly greater intraoperative i beta-END and pain as compared with those receiving placebo. The naloxone effect on intraoperative pain was a result of a difference in perceived unpleasantness. Both the fentanyl and diazepam groups had significantly lower intraoperative i beta-END and anxiety levels as compared with the placebo group. Norepinephrine levels increased significantly in response to surgical stress in all groups except the diazepam group. Postoperative circulating levels of i beta-END and norepinephrine and pain increased significantly from the 1 to 3-hour postoperative period for all groups, with the exception of stable norepinephrine levels observed in patients receiving diazepam. Results indicate that opiate antagonists stimulate and agonists suppress the release of i beta-END, possibly by affecting the patient's perceived level of pain and anxiety. In addition, the association of intraoperative hyperalgesia with naloxone predosing suggests that endogenous opioid peptides inhibit the perception of intraoperative pain even in the presence of concurrent local anesthesia.

Diazepam↗
PubMed1986

The medullary dorsal horn: a target for the expression of opiate effects on the perceived intensity of noxious heat.

We examined the effects of morphine microinjected into the medullary dorsal horn (MDH) on the ability of monkeys to detect temperature increases in the noxious heat range. Behavioral detection latency and the percentage of correct detections were used as measures of the perceived intensity of noxious heat stimuli. Three monkeys were trained to detect a change (T2) of 0.4, 0.6, or 1.0 degrees C from a previous noxious heat level of 46 degrees C (T1). Effects on attentional, motivational, and motoric aspects of the monkeys' behavior were assessed by having them detect innocuous cooling and visual stimuli in tasks of similar difficulty. Morphine (1, 3, and 10 micrograms) microinjected into the MDH produced a dose-dependent and stimulus-intensity-dependent increase in the latency to detection of the T2 stimuli. These effects were opiate receptor-mediated since they were antagonized by systemically administered naloxone (0.5 mg/kg, i.m.) given 40 min after the microinjection of morphine. There were no effects of morphine on the behavioral detection latencies to the innocuous cooling and visual stimuli, indicating that the effects of morphine were modality-specific and independent of changes in motivation, attention, or motoric ability. These data demonstrate a pharmacologically specific effect of opiates on the perceived intensity of noxious heat stimuli at the earliest central relay pathway transmitting noxious information.

Animals↗
PubMed1985

Descending serotonergic fibers in the dorsolateral and ventral funiculi of cat spinal cord.

Although there is much evidence for the presence of serotonergic fibers in the spinal gray matter, there is little evidence for the location of descending serotonergic fiber tracts in the spinal white matter. Using a highly sensitive immunocytochemical technique, we localized serotonin-immunoreactive axons throughout the white and gray matter of the spinal cord. Prominent concentrations of serotonergic axons were found in the dorsolateral and ventral funiculi. It is likely that these two descending fiber tracts contribute serotonergic input to the dorsal and ventral horns, respectively.

Animals↗
PubMed1985

Spinal lamina I neurons projecting to the parabrachial area of the cat midbrain.

We have observed a population of lamina I neurons in the cat that has projections to the parabrachial area (parabrachial and cuneiform nuclei). A subpopulation of these neurons also projects to the contralateral thalamus. The majority of projecting cells responded exclusively to noxious stimuli, a few wide-dynamic-range neurons were also observed. Conduction velocities for antidromic activation from the midbrain ranged from 1 to 18 m/s. We stained 14 cells intracellularly with horseradish peroxidase. These findings suggest that a major nociceptive projection pathway originating in lamina I and terminating in the parabrachial area exists in the cat.

Afferent Pathways↗
PubMed1985

Spinal neurons with branched axons traveling in both the dorsal and dorsolateral funiculi.

Antidromic search stimuli were delivered to cervical (C2-C3) dorsal and dorsolateral funiculi that were dissected apart from one another and from the rest of the spinal cord. Fifty-six neurons were antidromically identified in the dorsal horn of the lumbosacral enlargement. Of these neurons, 23 were activated antidromically from both the dorsal columns and the ipsilateral dorsolateral funiculus. The neurons were found at depths corresponding to laminae III and IV. About half of the neurons responded only to innocuous, tactile stimuli whereas the other half responded to both innocuous and noxious stimuli. The existence of neurons with branched axons ascending both the dorsal and dorsolateral funiculi raises the possibility that the dorsal column postsynaptic and spinocervical tracts may not be completely independent projections.

Animals↗
PubMed1985

Pain measurement: an overview.

The practice and theoretical basis of pain measurement is reviewed and critically examined in the areas of animal research, human subjects laboratory investigation and clinical study. The advantages and limitations of both physiological and behavioral methods are discussed in each area, and subjective report procedures are evaluated in human laboratory and clinical areas. The need for procedures that bridge these areas is emphasized and specific issues are identified. Progress in the technology of pain measurement over recent decades is reviewed and directions for future work are suggested.

Animals↗
PubMed1985

Intraspinal connections of dorsal column postsynaptic neurons in the cat--a physiological analysis.

Dorsal column postsynaptic (DCPS) neurons in the dorsal horn of the spinal cord have been identified by antidromic stimulation and intracellularly recorded in anesthetized cats. In about one-half of the cells, the antidromic stimulus evokes only an antidromic potential. This potential sometimes has an atypical shape due to penetration-induced depolarization. Atypical potentials are converted into typical antidromic spike potentials after intracellular injection of hyperpolarizing current. In the other one-half, the antidromic potentials are followed by postsynaptic activity. Intracellular analysis indicates that this postsynaptic activity is generated largely by activation of the intraspinal collaterals of A-beta primary afferents that are ascending the dorsal columns. Part of this postsynaptic activity has been produced monosynaptically. Polysnaptic responses are also evident; these are thought to be initiated by A-beta axons, desending axons from neurons in the dorsal column nuclei, or the local collaterals of the DCPS axons themselves. The results indicate that the DCPS system is nonlemniscal in nature and may be involved in those pain modulation systems that are activated by A-beta afferents.

Action Potentials↗