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Biomedical subjects

G Guilbaud

Publications and source records attributed to G Guilbaud.

At least 127 records · Page 7Linked to original sources

Depressive effects of morphine and of an enkephalinase inhibitor on responses of ventro-basal thalamic neurones to noxious stimuli.

It has been shown that the responses of VB thalamic neurones to noxious mechanical and thermal stimuli are strongly depressed by low doses of Morphine (0,03; 0,1; 1 mg/kg i.v.) and to a lesser extent by ES 52 (a highly potent Thiorphan derivative) injected at higher doses (5; 10 mg/kg i.v). This last effect was less easily reversed by Naloxone than was the depressive effect of Morphine. Moreover, ES 52 can facilitate activity of some thalamic neurones induced by non-noxious mechanical stimuli.

Amino Acids, Sulfur↗

Low dose of morphine strongly depresses responses of specific nociceptive neurones in the ventrobasal complex of the rat.

Effects of low intravenous doses of morphine (30, 100 and 1000 micrograms/kg) upon unitary responses of 22 'nociceptive' and 5 'non-nociceptive' units recorded in the ventrobasal (VB) complex of the rat were analyzed. The responses of the 'non-noxious' neurones were not depressed by morphine. By contrast, for all these doses there was a decrease of the total number of spikes and of the maximal firing rate of the responses of the noxious neurones. The depressive effect was significantly dose-related (with linear semi-logarithmic dose-response curve) and naloxone-reversible. Similar effects were observed upon responses to pinches and noxious heat. The ED50 which was close to 90 micrograms/kg for these thalamic responses to pinches is much more lower than that evaluated for spinal dorsal horn responses under the same anaesthetic conditions. Therefore the depressive effect of low doses observed for VB neurones seems to be mainly of supraspinal origin.

Animals↗

Effects of systemic naloxone upon ventrobasal thalamus neuronal responses in arthritic rats.

This study deals with the effect of various doses of systemic naloxone (10 microgram, 300 microgram, 1 mg/kg) upon activities of 21 ventrobasa thalamus neurons recorded in 20 rats rendered arthritic by injection of Freund's adjuvant into the tail. These neurons presented reproducible responses to movement and/or mild lateral pressure on a joint and were recorded for at least 30 min after naloxone administration. Several neurons (5) were tested with two doses. After intravenous injection of naloxone at the dose of 10 microgram/kg (10 cases) there was a rapid decrease of the responses. The maximum effect occurred at 15 min when the mean value expressed as a percentage of the control was 46.20 +/- 8.51% (n = 10, P less than 0.001). Recovery could be considered as complete at 30 min. At the dose of 300 microgram/kg (9 cases), the decrease in the responses was less important, variable from one neuron to another but significant between 5 and 20 min (mean = 67.43 +/- 9.00% at 20 min, n = 7, P less than 0.01). At the dose of 1 mg/kg (7 cases), there was no significant modification of the response. Spontaneous firing rate of the neurons was slightly but significantly increased after injection of the two highest doses and unmodified after the lowest. The relationship between the depressive effect produced by low doses of naloxone upon the neuronal responses, and the 'bi-directional' analgesic-hyperalgesic action of the drug, demonstrated in these suffering rats, is discussed.

Action Potentials↗

Somatic responses of ventrobasal thalamic neurones in polyarthritic rats.

Rats rendered polyarthritic by injection of Mycobacterium butyricum into the tail were used as a model for the study of 'chronic pain'. In such rats unitary responses of ventrobasal thalamic neurons to somatic stimulations were dramatically modified by comparison to those described in normal rats investigated in the same anaesthetic conditions. (1) Only the neurons with receptive fields located on inflamed areas (168/194 in 33 rats) have been considered in this study. 27/168 activated only by brushing displayed the classical properties of lemniscal responses; only 20/168 were activated exclusively by intense cutaneous stimuli and 13/168 already activated by light cutaneous stimuli had enhanced discharges when the stimulus intensity was increased. By contrast numerous units (108/168) were excited by mild stimulations applied to the joints or to adjacent cutaneous areas (82 were driven by joint movement and/or mild lateral pressure on the articulation, 26 by brushing the overlapping skin); these responses presented atypical characteristics and displayed unusual patterns with very long afterdischarges of duration several times that of the stimulus. (2) In 20 additional arthritic rats, responses to transcutaneous electrical stimulation (TES) and/or to noxious heat, were obtained for 34 neurones responding to joint stimuli. (a) 16 of 18 neurones tested with transcutaneous electrical stimulation had latencies of 25-100 ms, and thresholds of 1-4 mA (width of shock 2 ms). (b) Neurones activated by joint stimuli frequently responded to noxious heat (radiant or waterbath). Initially, their response thresholds tested in 16 neurones were higher by about 4 degrees C than those of 'noxious' VB neurones in normal rats; however, following sensitization to heat, thresholds were decreased by 4 degrees C. For 8 neurones there was a linear relation between stimulus intensity and responses. (3) Several different factors which could explain the important modification of neuronal responses in VB complex of arthritic rats by comparison with normal are proposed in the discussion.

Animals↗

Neuronal responses to noxious stimulation in rat somatosensory cortex.

Neuronal responses to noxious stimulation applied on the skin of the limbs or of the tail were studied in the somatosensory cortex of rats under Fluothane/nitrous oxyde anesthesia. Among 694 neurons, 56 responded to noxious stimulation only and 35 to noxious as well as non-noxious stimulation. The receptive fields of these neurons were often larger than those of neurons recorded during the same penetration but unresponsive to noxious stimulation. They were able to encode stimulus parameters such as temperature of a hot water bath or size of the skin area stimulated. They were more frequently found in the deepest half of the cortex. These results suggest that the cerebral somatosensory cortex plays a role in pain mechanisms.

Action Potentials↗

Aspirin clearly depresses responses of ventrobasal thalamus neurons to joint stimuli in arthritic rats.

This study dealt with the effect of aspirin upon activities of 17 ventrobasal thalamic neurons recorded in 17 rats rendered arthritic by injection of Freund's adjuvant into the tail. These neurons presented reproducible responses to mobilization and/or mild lateral pressure on a joint and were recorded for at least 40 min after aspirin administration. After intravenous injection of aspirin at the dose of 50 mg/kg (13 neurons tested), there was a progressive decrease in the number of spikes in the discharges. The maximum effect occurred at 30 min where the mean value of the response expressed as a percentage of the control was m = 34.62 +/- 7.5% (n = 13, p less than or equal to 0.001). Recovery was progressive and could be considered as complete at 60 min. By contrast, no significant modification of the spontaneous firing has been observed. With lower doses of aspirin (12.5 or 25 mg/kg tested with 4 neurons) there was respectively no clear depressive effect or only a transient decrease of the response.

Animals↗

Dose-dependent analgesic and hyperalgesic effects of systemic naloxone in arthritic rats.

The effects of various i.v. naloxone doses (10 microgram, 300 microgram, 600 microgram, 1 mg/kg) were studied upon vocalization threshold to foot-pressure in 30 normal rats and 70 rats with Freund's adjuvant-induced arthritis. In arthritic rats, the lowest naloxone doses yielded a clear increase in pressure required to trigger vocalization (i.e. were analgesic) while the highest dose (1 mg/kg) was hyperalgesic. In normal rats, naloxone never induced significant changes in the vocalization threshold.

Animals↗

[Electrophysiological responses of neurons of the ventrobasal complex of the thalamus to cutaneous and articular stimulation in rats with inflammatory polyarthritis].

Spontaneous and evoked activities of neurons recorded in the ventrobasal thalamic complex of polyarthritis Rats differ from those recorded in normal Rats. More than 1/3 of them displayed spontaneous paroxystic long discharges. Numerous neurons (41%) were excited by joint movement with responses showing very long after-discharges. Some of the responses elicited by light cutaneous stimuli were of the "lemniscal" type. Other ones displayed large bilateral receptive fields, located on inflammatory areas and showed long after-discharges. Only a few neurons were exclusively activated by intense cutaneous stimuli, contrasting with the higher cumulis in normal animals.

Action Potentials↗

Encoding of noxious heat messages in neurons of the ventrobasal thalamic complex of the rat.

Ventrobasal thalamic neurons responsive to noxious mechanical stimuli were tested with noxious heat stimuli graded in temperature, surface-area and duration. Experiments were performed by plunging the tail of intact, lightly anesthetized rats into a temperature-controlled water bath. Seventeen of 24 neurons encoded stimulus temperature by frequency of discharge although the responses of 6 of these 17 reached a plateau at the highest temperatures. Alternatively, the cell population might code stimulus temperature by a recruiting mechanism since response thresholds were distributed between 40 and 50 degrees C. Some units also increased their discharge in parallel with an increase in stimulus area and/or duration. Analyses of discharge patterns were performed. A decrease of discharge frequency during stimulation was not observed before several tens of seconds had elapsed. Thus, the average response of the cell population to 15, 30 and 60 sec stimuli showed no clear 'adaptation'. In our conditions, i.e. with most of the stimulations limited to a duration of 15 sec each, sensitization to heat was observed after 55 and 60 degrees C, but not after 50 degrees C. These data indicate that noxious heat stimulus parameters are coded at the thalamic level in the rat by both an increase in discharge and a progressive recruitment of units.

Animals↗

Responses of neurons of the nucleus raphe magnus to noxious stimuli.

Extra-cellular recordings were made from neurons located in nuclei raphé magnus (nRM) and reticularis paragigantocellularis (nRPGC) of intact rats. Noxious cutaneous and visceral stimuli elicited either excitatory or inhibitory effects, unaffected by innocuous stimuli while most of the noxious-inhibited neurons gave brief excitatory responses to innocuous brisk taps. It is suggested that the organization of these areas and their involvement in analgesic effects is much more complex than previously described.

Animals↗

Neuronal responses to cutaneous electrical and noxious mechanical stimuli in the nucleus reticularis thalami of the rat.

Responses of 81 neurons accurately localized in the nucleus reticularis thalami (RT) of moderately anesthetized rats were tested for response to noxious and non-noxious cutaneous stimuli. Spontaneous firing rates were very high (between 18 and 60 Hz) and regular. Non-noxious stimuli did not modify the activity of RT neurons. By contrast, in 62/81 RT neurons, noxious cutaneous mechanical stimuli induced a strong and short-latency depression of firing, irrespective of the location of the stimulus on the body surface. Intense (> 3 mA) transcutaneous electrical stimulation also elicited long-lasting depressions of the firing in most cases. The hypothesis of a possible role of the RT nucleus in inhibitory controls exerted upon noxious messages relayed in the thalamic ventrobasal nucleus is discussed.

Animals↗

Neurones responding to noxious stimulation in VB complex and caudal adjacent regions in the thalamus of the rat.

(1) 163 cells responding to mechanical cutaneous stimulation have been recorded in VB complex and caudal adjacent region in rats anaesthetized with a mixture of 2/3 N2O--1/3 O2 and 0.5% halothane. (2) 51 cells were exclusively activated by non-noxious cutaneous stimuli applied to restricted and contralateral receptive fields (RF) and had the classical characteristics of "lemniscal" responses. 93 cells responded only to noxious mechanical stimuli (N cells) and had either uni- or bilateral receptive fields. 19 cells responded both to noxious and non-noxious stimuli (NnN cells). (3) When tested with intense electrical stimuli applied transcutaneously or on the sural nerve, N and NnN cells responded with a late irregular discharge. Poststimulus histograms obtained in one-third of these units revealed that the late component was consistent with a C fibre input; some of responses were consistent with A delta fibre input. NnN cells also had a short latency discharge probably due to A alpha fibre involvement. (4) When tested with other intense stimuli such as noxious radiant heat or noxious visceral stimulation induced by intraperitoneal injection of bradykinin, N and NnN cells were strongly activated. (5) The different kinds of cells were scattered in VB and PO and no significant differences were found between cells recorded in VB and caudal adjacent region (PO); however, a rostrocaudal organization of the cells, according to the location of their RF on the caudal or rostral part of the body, was clear not only for the Nn cells but also for N and NnN cells.

Animals↗

The depressive effects of morphine on the C fibre response of dorsal horn neurones in the spinal rat pretreated or not by pCPA.

(1) The effects of morphine upon the transmission of nociceptive messages at the spinal level have been investigated in the spinal rat. The responses of dorsal horn cells induced by the activation of C fibres were depressed in all cases in a dose-dependent fashion, this effect being reversed by the opiate antagonist naloxone. An estimation of the ED50 at the cellular level leads to the value of 6.3 mg/kg. The responses to A delta fibres were also depressed dose-dependently whereas the responses to A alpha fibres were unaffected. This is a confirmation in the rat of the differential effects of morphine on responses of convergent units elicited by the stimulation of different fibres, as previously described in the cat. (2) The hypothesis of the participation of serotonergic terminals in these effects has been checked by comparing the preceding results to those obtained in pCPA pretreated animals. Two populations of units were observed in the latter group: two-thirds of cells showed a dose-response curve similar to that of the non-pretreated group whereas the remaining one-third were unaffected either by morphine or naloxone. It is concluded that, at least, two mechanisms are involved in the depressive effects of morphine at the spinal level, serotonergic terminals being implicated in one of these. (3) The lowering of spinal cord serotonin content was associated with a decrease of both the size of the excitatory receptive field (34%) and the activities related to C fibre input (36%) of the recorded dorsal horn cells. This result is discussed with reference to the excitatory or sensitizatory effect of serotonin upon chemoreceptors related to pain.

Animals↗