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Biomedical subjects

G Guilbaud

Publications and source records attributed to G Guilbaud.

At least 91 records · Page 5Linked to original sources
PubMed1989

Lack of significant changes in mu, delta opioid binding sites and neutral endopeptidase EC 3.4.24.11 in the brain and spinal cord of arthritic rats.

The possible changes in neutral endopeptidase EC 3.4.24.11 ("enkephalinase", NEP), mu and delta opioid binding sites, were investigated using in vitro quantitative radioautography in various regions of the central nervous system of the Freund's adjuvant-induced arthritic rat, a model of chronic pain. Enkephalinase was labeled by a specific tritiated inhibitor, [3H]N-[(2RS)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl]glycine ([3H]HACBO-Gly), while mu and delta opioid binding sites were selectively labelled with [3H]Tyr-D-Ala-Gly-(Me)Phe-Gly-ol ([3H]DAGO) and [3H]Tyr-D-Thr-Gly-Phe-Leu-Thr ([3H]DTLFT), respectively. As compared to controls, no significant modifications were found in NEP, mu or delta binding sites at both supraspinal and spinal levels of arthritic rats. These results suggest that the enhanced efficiency of exogenous opioids or endogenous enkephalins, reported to occur in this model of chronic inflammatory pain, are not directly related to changes in mu and delta opioid binding sites or steady state levels of NEP.

Animals↗
PubMed1989

Influence of a specific 5-HT3 antagonist on carrageenan-induced hyperalgesia in rats.

The effect of ICS 205-930 (ICS), a specific 5-HT3 antagonist, was studied on carrageenan (CAR)-induced rat paw inflammation to assess the involvement of endogenous released serotonin (5-HT) in the observed hyperalgesia. Studies were performed using a behavioural test, measuring the threshold stimulus necessary to elicit vocalization by gradually increasing pressure applied to the paw. When administered (s.c., in the CAR-injected paw) either 20 min before, simultaneously or 20 min after CAR, ICS (10(-11) mol/kg, i.e., 3.2 ng/kg) completely prevented the hyperalgesia in both the injected and non-injected hind paws. This effect was prolonged for 90 min, equivalent to the effect on CAR on 5-HT release. Moreover, ICS increased the vocalization threshold over the pre-drug values in normal and CAR-treated rats when injected both 20 min before and simultaneously with the polysaccharide. On the contrary, it did not reduce the hyperalgesia, when injected 2 h after CAR. ICS had no effect at any time of administration on paw oedema. These results suggest that the early inflammatory sensitization of peripheral nociceptors is mainly dependent on the release of serotonin and that the hyperalgesic effect of the monoamine involves 5-HT3(M) receptors which do not seem to be involved in the early development of oedema.

Animals↗
PubMed1988

[Analgesic action of sodium diclofenac: behavioral and electrophysiological study in normal and polyarthritic rats].

In a behavioural study, the effects of intravenous diclofenac in a range of doses were determined by measuring vocalization thresholds to paw pressure in normal and Freund's adjuvant-induced arthritic rats. In normal rats, 6 and 9 mg/kg diclofenac produced an increase in vocalization thresholds (mean threshold values were respectively 135.67 +/- 3.30 per cent and 157.41 +/- 4.62 per cent of the control at 30 min; n = 9 for each group), no effect resulting with 3 mg/kg. In arthritic rats, 3, 6 and 9 mg/kg diclofenac induced a clear analgesic effect (mean threshold values being 172.22 +/- 4.26 per cent, 201.76 +/- 4.76 per cent and 222.33 +/- 5.10 per cent respectively of the control at 25 min, n = 9 for each group), no effect being observed with 1.5 mg/kg. An electrophysiological study performed on arthritic rats considered the effect of 6 mg/kg diclofenac upon the neuronal ventrobasal thalamic responses induced by mode-rate stimulation of an inflamed joint. The responses were depressed by about 50 per cent, 20 minutes after the injection. These results show that diclofenac displays a direct effect on pain processing; this effect is more potent in arthritic rats than in normal rats.

Animals↗
PubMed1988

Noxious stimuli excite neurons in nucleus submedius of the normal and arthritic rat.

Anatomical studies have revealed the existence of an ascending pathway originating in the spinal cord and medullary dorsal horn, relaying in nucleus submedius (Sm) in medial thalamus and terminating in ventrolateral orbital cortex. It has been suggested that this pathway may be involved in the transmission of nociceptive information. In the present study extracellular recordings were obtained from neurons in Sm of anesthetized arthritic and normal rats. Mechanical and thermal stimuli were delivered to various regions of the body to determine the types of somatic stimuli which could activate Sm neurons. Over 40% of the 146 neurons studied responded to somatic stimuli. In the normal rats only high intensity mechanical and thermal stimuli were effective in inducing responses. In the arthritic rats lower intensity mechanical stimuli, joint movements and high intensity thermal stimuli were effective. Such stimuli produce nociceptive reactions in the freely moving arthritic rat. Almost all the responses were excitatory and generally lasted the entire duration of the 15-s stimuli employed. In some cases after-discharges were present. The receptive fields of the neurons were in almost all cases large and bilateral. These findings support the hypothesis that Sm may be involved in mediating the affective-motivational aspects of pain.

Animals↗
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↗
PubMed1988

Behavioural and electrophysiological evidence for an analgesic effect of a non-steroidal anti-inflammatory agent, sodium diclofenac.

The effects of various i.v. doses of diclofenac sodium (Voltaren, 1.5, 3, 6 and 9 mg/kg) were evaluated by measuring the vocalization threshold in response to paw pressure in normal and in Freund's adjuvant-induced arthritic rats. An electrophysiological study performed in parallel in arthritic rats considered the effects of 6 mg/kg i.v. diclofenac on ventrobasal thalamic neuronal responses driven by mild stimulation of an inflamed joint. In normal rats, 6 and 9 mg/kg i.v. diclofenac raised vocalization thresholds significantly (maximum vocalization thresholds were respectively 135.67 +/- 3.30% and 157.41 +/- 4.62% of the preinjection control at 30 min, n = 9 in each group), while no effect was observed with 3 mg/kg. In arthritic rats, i.v. doses of 3, 6 and 9 mg/kg diclofenac induced a clear analgesic effect (maximum vocalization thresholds were respectively 172.22 +/- 4.26, 201.78 +/- 4.76, 222.33 +/- 5.10% of the control at 25 min, n = 9 in each group), whereas a dose of 1.5 mg/kg i.v. did not raise the threshold. In arthritic rats, the VB neuronal responses were depressed by about 50% 20 min after an injection of 6 mg/kg i.v. diclofenac. These results clearly establish that diclofenac produces a dose-dependent analgesic effect, which is more potent in arthritic than in normal rats.

Action Potentials↗
PubMed1987

Paradoxical hyperalgesic effect of exceedingly low doses of systemic morphine in an animal model of persistent pain (Freund's adjuvant-induced arthritic rats).

The effects of exceedingly low doses of morphine (3-50 micrograms/kg i.v.) were studied upon the vocalization threshold induced by paw pressure in rats with Freund's adjuvant-induced arthritis. The highest dose used (50 micrograms/kg i.v.) clearly induced an analgesic effect. No significant modification of the vocalization threshold was observed with 30 micrograms/kg. By contrast, a significant hyperalgesic effect resulted with doses of 10 down to 3 micrograms/kg. Maximum hyperalgesia was observed with 6 micrograms/kg.

Animals↗
PubMed1987

Cross-tolerance between analgesic low doses of morphine and naloxone in arthritic rats.

The effects of acute injections of naloxone (3-3000 micrograms/kg i.v.) and morphine (100-1000 micrograms/kg i.v.) on the vocalization threshold induced by pressure on the paw were analyzed in adjuvant-induced arthritic rats pretreated either with naloxone or with morphine administered at low doses (9 micrograms/kg s.c. and 3000 micrograms/kg s.c., respectively) over 4 consecutive days. In naloxone-pretreated arthritic rats, the paradoxical analgesic effect of low doses of naloxone was almost abolished, and the potent analgesic effects of low doses of morphine were also strongly and dose-dependently reduced. In morphine-pretreated arthritic animals, the analgesic effect of low doses of naloxone was significantly attenuated. These results attest that a cross-tolerance with low analgesic doses of morphine and naloxone can be demonstrated in these chronic suffering animals. By contrast, in rats pretreated either with naloxone or morphine, the hyperalgesic effect of naloxone produced by higher doses persisted and even was unmasked for doses which were analgesic before the pretreatment. These data emphasize the involvement of opiate receptors different in their sensitivity and/or their functions in the two opposite effects of naloxone. They also suggest that opiate receptors and endorphinergic systems differ in normal animals and animals which experience persistent pain.

Animals↗
PubMed1987

Initial nociceptive sensitization in carrageenin-induced rat paw inflammation is dependent on amine autacoid mechanisms: electrophysiological and behavioural evidence obtained with a quaternary antihistamine, thiazinamium.

We have studied the ability of a quaternary antihistamine, thiazinamium, to inhibit the nociceptive sensitization that occurs early, during the first hour, following intraplantar injection of the polysaccharide carrageenin in the rat. Parallel studies were performed with an electrophysiological model (changes in responsiveness of ventro-basal thalamic cells driven by noxious stimulation of the paws), and a behavioural test (changes in threshold stimulus necessary to elicit vocalization by gradually increased pressure to the paws). When thiazinamium was given intravenously 10 min before carrageenin, no sensitization due to inflammation was found in either test. By contrast, when thiazinamium was administered 20 min after carrageenin, there was a clear sensitization in both tests that did not differ from that found in animals not treated with the antagonist. Paw oedema was also slightly decreased by pretreatment with thiazinamium. These results suggests that early inflammatory sensitization of peripheral nociceptors is mainly dependent on an initial release of histamine (and/or serotonin, since thiazinamium could also have some antiserotoninergic activity).

Animals↗
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↗
PubMed1987

Local and remote modifications of nociceptive sensitivity during carrageenin-induced inflammation in the rat.

The modifications of the threshold for vocalization induced by pressure on the paws (both hind paws and both forepaws) were monitored at different times (15 min-96 h) following intraplantar injection of the polysaccharide carrageenin in the rat. During the first 2 h following the carrageenin injection, a decrease in vocalization threshold was observed not only for the right, injected hind paw, but also, in some rats, on paws distant from the inflamed plantar region, especially the right forepaw. This hyperalgesic effect was suppressed by locally administered Xylocaine into the right hind paw. During the 4 days following the injection, the number of rats hyperalgesic in the injected paw progressively declined. Twenty-four hours after the carrageenin injection, only a few rats still presented a clear hyperalgesia in the non-injected paws.

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

Opioid receptor types and antinociceptive activity in chronic inflammation: both kappa- and mu-opiate agonistic effects are enhanced in arthritic rats.

The antinociceptive effects obtained in arthritic rats with morphine, the opioid mu-agonist DAGO [D-Ala2,MePhe4,Gly-ol5]enkephalin, the delta-selective agonist DTLET [D-Thr2, Leu5]enkephalyl-Thr, and the kappa-agonist U-50,488H were compared to their corresponding effects in normal animals and morphine-pretreated arthritic rats, respectively, using a paw pressure test. The effects of the mu- and kappa-agonists were increased in arthritic rats. While morphine-treated rats were cross-tolerant to the mu- and kappa-agonists, no tolerance to the delta-selective agonist was found. The possibility that the potent action of morphine in this model for chronic inflammatory pain is mediated partly through kappa-mechanisms is discussed.

Analgesics↗
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↗
PubMed1986

Repeated low doses of morphine induce a rapid tolerance in arthritic rats but a potentiation of opiate analgesia in normal animals.

The effect of repeated low doses of morphine (0.3-3 mg/kg s.c., twice daily for 4 days) on subsequent sensitivity to the antinociceptive effect of morphine was tested in arthritic and normal rats. Chronic morphine induces tolerance in arthritic rats. This tolerance develops rapidly since it is clearly present after one day of treatment. By contrast, in normal animals similarly treated, a potentiation of morphine analgesia was observed.

Animals↗