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ABSTRACT: Thalamic neurons are known to switch their firing from a tonic pattern during wakefulness to a bursting pattern during sleep. Several studies have described the existence of bursting activity in awake chronic pain patients and have suggested that this activity is abnormal and may be related to their pain. However, we have frequently observed bursting activity in awake non-pain patients suggesting that there may not be a causal relationship between thalamic bursting activity and chronic pain. To examine this issue more rigorously we compared the incidence and pattern of bursting activity of lateral thalamic neurons of both pain and non-pain patients in a state of wakefulness. Recordings were obtained from lateral thalamic areas of different groups of patients (n = 91) suffering from pain disorders (e.g. anaesthesia dolorosa, phantom limb pain, trigeminal neuralgia, post-stroke pain) and motor disorders (e.g. Parkinson's disease, essential tremor) during stereotactic surgical procedures for the treatment of pain and movement disorders. Burst indices (the number of bursting cells per electrode track) were computed for all the explorations in the two groups. The burst indices in the pain and non-pain groups (1.73 +/- 0.28 and 1.14 +/- 0.16, respectively) were not significantly different from each other. The bursts were analyzed to see if they fulfilled the criteria of low-threshold calcium spike (LTS)-evoked bursts characterized by (i) a shortening of the first interspike interval with an increase in the number of interspike intervals in the burst and also (ii) a progressive prolongation of successive interspike intervals. LTS-evoked bursts were identified in 27/47 (57%) bursting cells in pain patients and 15/32 (47%) cells in non-pain patients. These data demonstrate that the occurrence of bursting activity and of LTS-evoked bursts in the human thalamus is prevalent in both pain and non-pain patients. This suggests that the bursting activity of thalamic neurons in pain patients is not necessarily related to the occurrence of their pain.
Pain 05/1999; 80(3):567-75. · 5.78 Impact Factor
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ABSTRACT: Surprisingly little is known concerning the central processing of innocuous thermal somatosensory information. The aim of the present study was to obtain quantitative data on the characteristics of neurons in the rat superficial medullary dorsal horn (sMDH) that responded to innocuous thermal stimulation of the rat's face and tongue. Single-unit extracellular recordings were obtained in chloralose-urethane anesthetized rats. A total of 153 thermoreceptive neurons was studied. Of these, 146 were excited by cooling and inhibited by warming and were classified as COLD cells. The remaining seven cells were excited by innocuous warming of the skin or tongue. Of 123 COLD cells tested, 33% were excited by touch and 22% by pinch stimuli delivered to the thermoreceptive field. Of the 50 COLD cells tested, 46% were excited also by noxious heating (> or = 50 degrees C for 5 s). Most (82/121) of the receptive fields were located on the upper lip, 25 on the tongue, and most of the remaining on the lower lip. Receptive fields were generally small (1-5 mm2). In some experiments, electrical stimulation in the thalamus was performed, and nine COLD cells could be activated antidromically. The responses of 38 COLD cells to incremental 5 degrees C cooling steps were examined quantitatively. Thermal stimuli were applied to facial or lingual receptive fields of sMDH neurons with a computer-controlled Peltier thermode starting from 33 degrees C, decreasing to 8 or 3 degrees C, and returning to 33 degrees C. Most COLD cells (26/38) had both static and dynamic responses; 7 had mainly dynamic and 5 mainly static responses to step decreases in temperature. Rat sMDH COLD cells could be classified into three groups depending on their stimulus-response functions. The first group (Type 1, n = 19) had a bell-shaped static stimulus response function. The second group (Type 2) had a high maintained or increasing static firing rate as the temperature decreased < 18 degrees C (n = 10). Type 3 COLD cells had mainly dynamic properties (n = 7). Many of the cells in all groups were excited by noxious mechanical stimulation. Type 2 cells differed from the other two groups in that most did not respond to noxious thermal stimuli (hot) and many responded to innocuous tactile stimuli. Neurons from each of the three groups of COLD cells could be activated antidromically from contralateral thalamus. These data suggest that there is little central processing of thermal information at the first central synapse for Type 1 neurons, however, the responses of the other two types may be due to central processing and convergence. The demonstration of rat sMDH COLD cells with distinctive stimulus-response functions to thermal shifts suggests separate functional roles of these neurons in the ascending thermal sensory pathway.
Journal of Neurophysiology 07/1997; 77(6):3252-66. · 3.32 Impact Factor
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ABSTRACT: The firing patterns of thalamic neurons in mammals undergo a dramatic change as the animal's state changes between sleep and wakefulness. During sleep the normal tonic firing of thalamic neurons changes into a slower bursting mode characterized by repetitive activation of a low-threshold calcium (Ca2+) current. The present report describes the patterns of thalamic neuronal firing during sleep and wakefulness in one human patient. Extracellular single neuron activity was recorded during functional stereotactic surgery in the thalamus of a patient with chronic pain, who was observed to fall asleep during the recording. Evolutive power spectra of the thalamic slow wave were used in place of cortical encephalography to confirm the patient's states of sleep and wakefulness. Twenty-nine sites were observed in motor and somatosensory thalamus (Vop, Vim, and Vc) that were characterized by the presence of neurons with bursting activity when the patient was asleep. Such bursting was not observed in the patient when she was awakened. At 14 of these sites we were able to discriminate the bursting activity of single units. In each case the cell stopped firing or its bursting was replaced by a tonic firing pattern when the patient was awakened. In three cases the patient began to lapse back into sleep and the neuron resumed firing in a bursting pattern once again. None of these units had a peripheral receptive field (RF), while several other units recorded in nearby regions that did not fire in a bursting pattern during sleep had kinesthetic or cutaneous RFs. Analysis of the intraburst firing pattern revealed increasing interspike intervals (ISI) for successive action potentials in a burst and that the duration of the first ISI in the burst decreased as the number of ISIs increased. This pattern is similar to that reported to occur as a result of a calcium spike. These data have confirmed for the first time that state-dependent changes in thalamic firing exist in the human and that the physiological substrates at the thalamic level that are involved in human sleep are similar to those observed in animals.
Experimental Brain Research 03/1997; 113(2):273-82. · 2.39 Impact Factor
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ABSTRACT: The activities of 39 single cells, located in the ventroposterior nucleus of the rat thalamus, were recorded from rats deeply anaesthetized with xylazine and ketamine. The activity of each neurone was recorded before and during noxious tail heating. In all, 17 neurones were excited, 11 were inhibited, and 11 were not affected by the noxious stimulation. The possible function of each type of response in the coding of nociceptive information is discussed.
Physiological research / Academia Scientiarum Bohemoslovaca 02/1997; 46(1):53-8. · 1.55 Impact Factor
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ABSTRACT: Neurons in the lateral thalamus of a patient undergoing stereotactic surgery were found to fire in a characteristic bursting pattern only when the patient was asleep. These novel observations are consistent with animal studies in which the tonic firing pattern of thalamic neurons during wakefulness changes to a bursting pattern during slow-wave sleep.
Stereotactic and Functional Neurosurgery 02/1995; 65(1-4):125-9. · 1.85 Impact Factor
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ABSTRACT: The spiking activity of single units and their corresponding mass activity in the rostral ventromedial medulla (RVM) was recorded simultaneously in rats that were either awake or anesthetized with pentobarbital or ketamine. Autocorrelograms and cross-correlograms were calculated to illustrate the distribution of interspike intervals under each of these conditions. The spontaneous activity in both anesthetized groups, but not the awake group, displayed a low incidence for short intervals (about 1-36 ms) between spikes. However, this low incidence of short interspike intervals was found in some awake rats following the administration of subanesthetic dosages of ketamine, pentobarbital, or morphine. The occurrences, or lack of occurrences of these short interspike intervals may be a marker for the anesthetized state of the rat. A basal spiking pattern, as illustrated by three different types of correlograms, was observed, and these basal patterns did not usually change after the administration of morphine to awake or anesthetized rats, even though the cells became excited or inhibited. Cross-correlograms revealed that the synapses between "on" and "off" cells might sometimes be inhibitory, while at other times they might be excitatory; however, cells of the same class mainly shared excitatory connections. In summary, ketamine and pentobarbital do alter the firing patterns of individual neurons in the RVM, but, no matter what state the rat is in, the activity of individual RVM neurons is strongly related to the activity of other neurons in the local network.
Experimental Brain Research 02/1995; 106(2):283-90. · 2.39 Impact Factor
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ABSTRACT: Past research investigating the rostral ventromedial medulla (RVM) in anesthetized animals has found two distinct classes of cells, ON and OFF, noted for their distinct responses to noxious stimuli and to morphine. However, only one class (ON) has been found in the awake animal paradigm. We report in this paper that we have found both the ON and OFF cell responses to morphine in the awake rat.
Brain Research 03/1993; 604(1-2):331-3. · 2.73 Impact Factor
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ABSTRACT: Two classes of cells in the rostral ventromedial medulla (RVM), ON and OFF, are important in the descending modulation of noxious input. It is thought that these two cell classes communicate, at a local level, with each other to control the RVM's descending modulation. Systemic morphine was given to rats anaesthetized with either pentobarbital (a GABA agonist) or with ketamine (a non-competitive NMDA receptor antagonist) and xylazine. The spiking activity of the ON and OFF cells was recorded. The typical ON cell inhibition by morphine was observed in rats under both anaesthetics. However, the OFF cell excitatory response to morphine was seen in the ketamine but not in the pentobarbital-anaesthetized animals. The implications for a GABAergic connection between these two classes of cells are discussed.
Neuroscience Letters 02/1993; 149(2):119-22. · 2.11 Impact Factor
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ABSTRACT: Although a considerable amount of knowledge has been accumulated about the activity of individual nerve cells in the brain, little is known about their mutual interactions at the local level. The method presented in this paper allows the reconstruction of functional relations within a group of neurons as recorded by a single microelectrode. Data are sampled at 10 or 13 kHz. Prominent spikes produced by one or more single cells are selected and sorted by K-means cluster analysis. The activities of single cells are then related to the background firing of neurons in their vicinity. Auto-correlograms of the leading cells, auto-correlograms of the background cells (mass correlograms) and cross-correlograms between these two levels of firing are computed and evaluated. The statistical probability of mutual interactions is determined, and the statistically significant, most common interspike intervals are stored and attributed to real pairs of spikes in the original record. Selected pairs of spikes, characterized by statistically significant intervals between them, are then assembled into a working model of the system. This method has revealed substantial differences between the information processing in the visual cortex, the inferior colliculus, the rostral ventromedial medulla and the ventrobasal complex of the thalamus. Even short 1-s records of the multiple neuronal activity may provide meaningful and statistically significant results.
Journal of Neuroscience Methods 07/1992; 43(1):1-12. · 1.98 Impact Factor
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ABSTRACT: Thalamic neurons are known to switch their firing from a tonic pattern during wakefulness to a bursting pattern during sleep. Several studies have described the existence of bursting activity in awake chronic pain patients and have suggested that this activity is abnormal and may be related to their pain. However, we have frequently observed bursting activity in awake non-pain patients suggesting that there may not be a causal relationship between thalamic bursting activity and chronic pain. To examine this issue more rigorously we compared the incidence and pattern of bursting activity of lateral thalamic neurons of both pain and non-pain patients in a state of wakefulness. Recordings were obtained from lateral thalamic areas of different groups of patients (n=91) suffering from pain disorders (e.g. anaesthesia dolorosa, phantom limb pain, trigeminal neuralgia, post-stroke pain) and motor disorders (e.g. Parkinson's disease, essential tremor) during stereotactic surgical procedures for the treatment of pain and movement disorders. Burst indices (the number of bursting cells per electrode track) were computed for all the explorations in the two groups. The burst indices in the pain and non-pain groups (1.73±0.28 and 1.14±0.16, respectively) were not significantly different from each other. The bursts were analyzed to see if they fulfilled the criteria of low-threshold calcium spike (LTS)-evoked bursts characterized by (i) a shortening of the first interspike interval with an increase in the number of interspike intervals in the burst and also (ii) a progressive prolongation of successive interspike intervals. LTS-evoked bursts were identified in 27/47 (57%) bursting cells in pain patients and 15/32 (47%) cells in non-pain patients. These data demonstrate that the occurrence of bursting activity and of LTS-evoked bursts in the human thalamus is prevalent in both pain and non-pain patients. This suggests that the bursting activity of thalamic neurons in pain patients is not necessarily related to the occurrence of their pain.
Pain.
