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M Gautron

Publications and source records attributed to M Gautron.

At least 37 records · Page 2Linked to original sources
PubMed1988

Behavioural and electrophysiological studies on the paradoxical antinociceptive effects of an extremely low dose of naloxone in an animal model of acute and localized inflammation.

We have previously described the paradoxical antinociceptive effect of low doses of an opiate antagonist, naloxone, in rats suffering from chronic arthritis induced by Freund's adjuvant. In the present work, the appearance of this naloxone sensitivity was studied, using a model of inflammatory hyperalgesia with a more rapid onset, namely carrageenin-induced rat paw edema. In these animals, an extremely low dose of naloxone (3 micrograms/kg i.v.), induced a clear antinociceptive effect (as gauged by the vocalisation threshold to paw pressure), which was observed for both the edematous and the contralateral hind-paw. Small and transient 1 h after carrageenin injection, this effect increased progressively 4 h and 24 h later, reaching a level comparable to that observed with morphine 1 mg/kg i.v. in normal rats, at 24 h. Electrophysiological studies performed in parallel, confirmed the behavioural data so that 24 h after the injection of carrageenin, naloxone (3 micrograms/kg i.v.) reduced the VB thalamic neuronal responses elicited by stimulation of the inflamed paw by 50%. Hypothesis concerning the mechanisms of the paradoxical action of naloxone in models of inflammatory hyperalgesia are discussed.

Action Potentials↗
PubMed1987

Neuronal response thresholds to and encoding of thermal stimuli during carrageenin-hyperalgesic-inflammation in the ventro-basal thalamus of the rat.

This study analyzed neuronal encoding and response thresholds to thermal stimuli at the ventro-basal (V.B.) thalamus level during a hyperalgesic inflammation induced by intra-plantar injection of carrageenin in the rat. The threshold and the encoding capacity of the cells were studied during two phases of the inflammatory process, namely the "acute" phase (the first two hours following the injection), and "sub-acute" phase 24 h after). In this second phase the hyperalgesia was verified using a behavioral nociceptive test, just prior to the recording session. Only VB neurones with a receptive field that included the injected paw were considered. In the acute phase, neurones exclusively driven by noxious stimuli were studied before and during the first two hours following the induction of the inflammatory oedema. In the sub-acute phase two groups of neurones which, on the basis of our previous studies, were presumably involved in the transmission of messages giving rise to the hyperalgesia could be separated: a group of neurones which were driven by intense mechanical stimuli and another group driven by moderate mechanical stimulation applied to the inflamed joints and/or the surrounding cutaneous areas. In the "acute" phase there was a dramatic lowering (by about 4 degrees C) of the response threshold of the neurones when the thermal stimulus was applied to the injected paw, although their threshold to the mechanical stimulus was still high. A linear encoding of the bath temperature used as a stimulus was observed for both the injected and the non-injected paws. For a few neurones, a leftward shift of the stimulus-response curve was found for the inflamed limb. In the "sub-acute" phase, neurones with high thresholds to the mechanical indentations still exhibited a low response threshold to the thermal stimulation, not only from the injected but also from the non-injected paw. The other group of neurones responded with relatively low thresholds to the both stimulus modalities. By contrast to the acute phase, the two groups of neurones exhibited only a weak ability to encode the stimulus intensity especially when the stimulus was applied to the inflamed paw. Both peripheral and central mechanisms are likely to be involved in the modifications of response threshold and encoding capacity at the VB thalamus level seen in these conditions of hyperalgesic inflammation. The differential time course of the responses to a liminal or to a supra-liminal temperature during the inflammation, are discussed in reference to some of the mismatches occurring in clinical situations of hyperalgesia.

Action Potentials↗
PubMed1987

Thresholds and encoding of neuronal responses to mechanical stimuli in the ventro-basal thalamus during carrageenin-induced hyperalgesic inflammation in the rat.

Neuronal response thresholds and the encoding of mechanical stimulus intensity in the ventro-basal (VB) thalamus was analyzed in anaesthetized rats before and during the first two hours following induction of hyperalgesic inflammation. This inflammation was induced by the intra-plantar injection of carrageenin in the hindpaw contralateral to the recorded neurones. Only neurones exclusively driven by noxious stimuli and with a receptive field on or including the injected paw were considered. In this early phase of the inflammatory process, there was no significant modification of the response threshold to the mechanical stimulus (indentation of about 300 micron). This suggests the involvement of additional neuronal population(s) to account for the decrease in the vocalisation threshold to pressure observed in the freely moving animal at this time of the inflammation. A liner encoding of the indentation depth was observed before and after the carrageenin injection although the slope of the stimulus response-curve was steeper after the injection. The data emphasize that the carrageenin-sensitization acts differentially on the liminal and supra-liminal responses of the same neurone to a skin indentation, since in the first hour following the initiation of the inflammation the sensitization is essentially observed for responses obtained with stimulus intensity largely above the threshold value. With regard to previous observations using thermal stimulation, the results also illustrate that the carrageenin induced sensitization of responses differs depending on the stimulus intensity and modality used.

Animals↗
PubMed1986

Differential depressive action of two mu and delta opioid ligands on neuronal responses to noxious stimuli in the thalamic ventrobasal complex of rat.

In the present investigation the effects of selective agonists for mu (Tyr-D-Ala-Me-Phe-Gly-ol (DAGO)) and delta (Tyr-D-Thr-Gly-Phe-Leu-Thr (DTLET)) opioid receptors on neuronal activities induced by noxious cutaneous stimuli in the rat ventrobasal (VB) thalamus were analyzed. The two agonists produced a clear depressive action on thermal as well as mechanical noxious stimuli. The depressive action of DTLET (3 mg/kg i.v.) was lower and of shorter duration than that of DAGO (2 mg/kg i.v.). However, this effect is unambiguously related to the selective stimulation of opioid receptors since a consistent effect was also observed for a dose as low as 1.5 mg/kg i.v. of DTLET. Moreover, DTLET effect needs a high concentration of naloxone (0.5 mg/kg i.v.) to be reversed, while DAGO effect is totally reversed with 0.1 mg/kg i.v.

Action Potentials↗
PubMed1986

Modifications in the responsiveness of rat ventrobasal thalamic neurons at different stages of carrageenin-produced inflammation.

The present study was aimed at analyzing the responsiveness of the ventrobasal (VB) thalamic neurons in rats presenting with a hyperalgic carrageenin-produced inflammation. The following were studied: the responses of the same VB neuron, before and 15-145 min after the plantar injection of carrageenin in a part of its receptive field (RF) (acute phase); the responses of VB neurons located in the thalamus contralateral to the hyperalgesic inflamed paw, 24-96 h after the injection (subacute phase); and the effect of a local anesthetic injected in the inflamed paw, and that of an intravenous injection of Aspirin, on neuronal response modifications. Responses of VB neurons initially activated by light tactile stimuli (group 1; n = 4) and by moderate joint stimulation (group 3; n = 4) were not modified in the early period following the carrageenin injection. By contrast, in the first few minutes following the injection. VB neurons exclusively driven by noxious mechanical and thermal stimuli (group 2; n = 23), exhibited a clear enhancement of their responses, which persisted during the observation period. These modifications were also observed for responses obtained from part of the RF remote from the injection site; moreover there was an extension of the RF to areas distant from the injured paw. The local injection of an anesthetic (Xylocaine) in this paw, suppressed the modifications of responses of group 2 neurons, elicited not only from the injected paw, but also from the remote parts of the RF. At this time Aspirin was almost inefficient (even at the dose of 100 mg/kg) on responses of these group 2 neurons. In the subacute phase responses of 72 somatosensory neurons were analyzed. Twenty-five of 72 responded to rapid repetitive light tactile stimulation applied on a small contralateral RF (group 1); their responses were similar to those encountered in a normal situation. Thirty-three of 72 neurons responded to intense mechanical stimuli such as pinches (group 2). For half of them the response characteristics were similar to those described in the normal rat; for the other half responses appeared 'faded': short duration; absence of after-discharge; poor reproducibility. Fourteen of 72 neurons responded to moderate stimulation of the joints, deep tissues and/or surrounding cutaneous areas of the inflamed paw (group 3). Their RF was mostly unilateral, i.e. contralateral to the recording site; the responses were sustained during the stimulation but rarely exhibited after-discharge.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1985

Electrophysiological evidence for a role of the anterolateral quadrant of the spinal cord in the transmission of noxious messages to the thalamic ventrobasal complex in the rat.

Responses to noxious mechanical and thermal stimulation applied to the hindpaws were recorded extracellularly from the same neurons of the ventrobasal complex of the rat thalamus (VB) before and after lesions of various areas of the cervical cord in order to determine the pathways carrying the afferent messages. It was demonstrated that lesions of the dorsal and dorsolateral portions of the cord failed to eliminate the VB neuronal responses to noxious stimulation. By contrast, lesion of one anterolateral quadrant eliminated the responses to a noxious stimulation applied to the hindpaw contralateral to the lesion. This occurred whether the lesion was ipsilateral or contralateral to the recording site. From the present study and the data in the literature, it is concluded that the fibers of the spino-thalamic tract which are completely crossed in the spinal cord, travel in the anterolateral quadrant and project directly onto the VB, are involved in the transmission of noxious messages from the cord to the VB neurons. This conclusion indicates that the VB neuronal responses to noxious stimulation of the hindpaw ipsilateral to the recording site depend on the spinothalamic projection to the opposite ventrobasal complex. This therefore suggests that some noxious messages which reach a particular VB neuron are conveyed via the opposite VB and the existence of a thalamo-cortico-thalamic loop is discussed.

Animals↗
PubMed1984

[Acute inflammation and hyperalgesia: their consequences on the responses of various neurons of the ventrobasal thalamic complex in rats].

Neuronal responses elicited in the ventrobasal thalamic complex by somatic noxious stimuli are facilitated early in the course of carrageenin-induced acute inflammation, (i) the responses evoked by noxious stimuli applied on the injected paw were enhanced (50-300%); (ii) similar increase was also observed for responses obtained from preexisting receptive fields distinct from the injection site; (iii) moreover, new responses could be elicited by noxious stimuli applied in initially unresponsive areas. These data suggest the involvement of central mechanisms underlying these changes.

Animals↗
PubMed1983

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↗
PubMed1983

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↗
PubMed1982

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↗
PubMed1982

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↗
PubMed1982

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↗
PubMed1981

[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↗
PubMed1980

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↗
PubMed1980

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↗
PubMed1980

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↗
PubMed1980

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↗