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V Kayser

Publications and source records attributed to V Kayser.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1986

Behavioral evidence for a crossed ascending pathway for pain transmission in the anterolateral quadrant of the rat spinal cord.

Thresholds of two behavioral responses to noxious pressure of the hindpaws (withdrawal, vocalization) were analyzed before and 3 weeks after a lesion of various quadrants of the spinal cord at the cervical level. The threshold of the spinal reflex could not be modified. Threshold of vocalization elicited by the pressure of one hindpaw was significantly increased when, and only when, the opposite ventrolateral quadrant was cut. These results emphasize the role of the lateral spinothalamic tract in the transmission of noxious messages.

Afferent Pathways↗
PubMed1986

Analgesia produced by low doses of the opiate antagonist naloxone in arthritic rats is reduced in morphine-tolerant animals.

In a model of experimental chronic pain (adjuvant-induced arthritic rats), low doses of the opiate antagonist naloxone produced a profound analgesia. Maximum analgesia was seen with 3 micrograms/kg (i.v.). In contrast, hyperalgesia was obtained with much higher doses (1-3 mg/kg, i.v.). The hyperalgesic effects were not affected in arthritic animals rendered tolerant to morphine, but the paradoxical analgesic effects were significantly reduced. This decrease suggests that naloxone analgesia involves interaction with opiate receptors and that the operation of endorphinergic systems differs in normal animals and animals which experience persistent pain.

Animals↗
PubMed1985

Can tolerance to morphine be induced in arthritic rats?

The effects of acute injections of morphine (0.1-1 mg/kg i.v.) upon vocalization threshold elicited by pressure of the paw were analyzed in normal and arthritic rats, both groups being initially pretreated with calculated doses of morphine. The analgesic effects of morphine were greatly reduced in both groups of chronically morphine-treated rats. The lowest doses (0.1 mg/kg in normal rats; 0.1 and 0.3 mg/kg in arthritic animals) became totally ineffective, while the highest dose (1 mg/kg) elicited a threshold increase only equivalent to that induced by 0.3 mg/kg in non-tolerant chronically vehicle-treated rats. Tolerance to morphine can be induced in rats suffering from arthritis, and appeared to be more complete than in normal rats.

Animals↗
PubMed1984

Further evidence for changes in the responsiveness of somatosensory neurons in arthritic rats: a study of the posterior intralaminar region of the thalamus.

In 21 arthritic rats, responses of 128 somatosensory neurons located in the intralaminar region of the thalamus were studied. This study reveals a profound change in the responses of intralaminar neurons in such rats, as compared with those observed in normal animals. Most of the activated neurons (98/120) were driven by moderate mechanical stimulation applied to the joints, while only few neurons (7/120) were exclusively driven by intense mechanical stimuli such as pinch. In addition numerous activated neurons were located in the ascending branch of the CL where in normal rat, few somatosensory 'noxious' neurons have been recorded.

Animals↗
PubMed1984

Further evidence for a bidirectional effect of naloxone on the pain threshold in tolerant and non-tolerant arthritic rats.

In arthritic rats, low doses of naloxone induced powerful analgesic effects (as gauged by the vocalization threshold elicited by pressure on the paw) which were marked for 3 and 6 micrograms/kg IV, whereas high doses (1000 and 3000 micrograms/kg IV) induced hyperalgesia. This bidirectional effect persisted in arthritic rats rendered tolerant to morphine, but whereas the analgesic effects were suppressed or reduced, the hyperalgesic effects induced by the higher doses were unchanged. These results suggest that the analgesic and hyperalgesic effects might be mediated by different systems.

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

Low dose of morphine microinjected in the ventral periaqueductal gray matter of the rat depresses responses of nociceptive ventrobasal thalamic neurons.

The effect of low doses of morphine (2 micrograms in 0.2 microliter) microinjected in the periaqueductal gray matter (PAG) was studied on responses of 11 nociceptive (N) and 3 non-nociceptive (Nn) ventrobasal (VB) thalamic neurons in lightly anesthetized rats. Responses of Nn neurons were unmodified but their receptive field was consistently enlarged during 50-60 min. Responses of N neurons to calibrated pinches were strongly depressed when the microinjection site was located in the PAG or in the dorsal raphe (NDR) (7 cases), and not significantly changed when morphine was applied in the dorsal PAG. For the 7 depressed neurons, the mean value of the responses expressed as a percentage of the control was 20.12 +/- 5.17, 15 min after morphine application. This depressive effect was variably reversed by naloxone (0.1-0.5 mg/kg).

Animals↗
PubMed1983

The analgesic effects of morphine, but not those of the enkephalinase inhibitor thiorphan, are enhanced in arthritic rats.

The effects of various i.v. doses of morphine (0.1, 0.3 and 1 mg/kg) and of thiorphan, an inhibitor of enkephalinase (0.7, 2.5, 5, 10 and 15 mg/kg), were studied upon the vocalization threshold to foot pressure in normal rats and rats with Freund's adjuvant-induced arthritis. The vocalization threshold in arthritic rats was, before any injections, significantly lower than in normal rats (mean pressure threshold for vocalization: 115.2 g +/- 14.7 (n = 152) for arthritic rats vs 182.5 g +/- 21.3 for normal rats (n = 152). The various doses of morphine in raising the vocalization threshold were more efficient in arthritic than in normal rats (maximum vocalization threshold (% of control) following 1 mg/kg morphine = 225.70 +/- 10.21 in arthritic rats vs 140.75 +/- 6.87 in normal rats, n = 9 in each case). This effect was dose-dependent, and in every case, naloxone-reversible. Injected at doses of 5-15 mg/kg, thiorphan increased the vocalization threshold (maximum = 223.91% +/- 11.96 in arthritic rats vs 223.30% +/- 5.93 in normal rats for 15 mg/kg i.v., n = 9 for each group). This effect was not greater in arthritic than in normal rats. The dose of 2.5 mg/kg of thiorphan was insufficient. Administered at 0.7 mg/kg, thiorphan significantly decreased the vocalization threshold in the arthritic rats only. These effects of thiorphan were all naloxone-reversible using doses of naloxone which were one-hundredth of those of thiorphan.

Amino Acids, Sulfur↗
PubMed1983

Further evidence for a strong depressive effect of low doses of morphine on VB thalamic neuronal responses (a study on arthritic rats).

The effects of various i.v. morphine doses (30, 100 and 1000 micrograms/kg) were studied upon unitary ventral basal (VB) neuronal responses elicited by joint stimulation in 24 Freund's adjuvant induced arthritic rats. The depressive effect of morphine was significantly dose-related and generally naloxone-reversible; however there were sometimes some difficulties to reverse morphine effect with the lowest dose of naloxone (10 micrograms/kg). The effect of morphine was not significantly different from that obtained in normal rats upon responses of specific nociceptive VB neurons. Although these results do not explain enhancement of morphine analgesia in arthritic rats by comparison with normal rats, they do confirm efficiency of low doses of morphine upon VB neuronal responses elicited by stimuli which induce nociceptive reaction in freely moving animals.

Animals↗