Biomedical subjects

G Guilbaud

Publications and source records attributed to G Guilbaud.

At least 37 records · Page 2Linked to original sources

PubMed1996

The antinociceptive activity of kappa- but not delta-opioid receptor agonists is maintained in morphine-tolerant neuropathic rats.

The antinociceptive effect of the preferential mu-opioid receptor agonist morphine (1 mg/kg i.v.), the delta-opioid receptor agonists, DTLET ([D-Thr2,Leu5]enkephalin-Thr) (3 and 6 mg/kg i.v.) and BUBUC ([D-Cys(StBu)2,Leu5]enkephalin-Thr(OtBu) (3 mg/kg i.v.), and the kappa-opioid receptor agonist U-69,593 (trans-3,4-dichloro-N-methyl-N-[7-(1-pyrrolidinyl)cyclohexil]benze neacetamide methanesulfonate) (0.25, 0.5 and 0.75 mg/kg i.v.) was evaluated in mononeuropathic (chronic constriction of the common sciatic nerve) rats. The rats were pretreated s.c. with 10 mg/kg of morphine, or saline, twice daily from day 12 to day 16 after the surgery. In morphine-pretreated rats, the antinociceptive effect of morphine on the vocalization threshold to paw pressure was greatly reduced, as compared to the saline-pretreated group. The antinociceptive effect of DTLET and BUBUC had also disappeared in the morphine-pretreated rats. By contrast, the potent antinociceptive effect of U-69,593 was not affected by the morphine pretreatment. Furthermore, the effect of U-69,593 was reversed by the specific kappa-opioid receptor antagonist nor-binaltorphimine (1 and 2 mg/kg i.v.). These results suggest that in mononeuropathic rats, morphine pretreatment results in cross-tolerance to delta- but not to kappa-opioid receptor agonists.

Analgesics, Opioid↗

PubMed1996

Estrous and sex variations in vocalization thresholds to hindpaw and tail pressure stimulation in the rat.

This study examined sex and estrous differences in vocalization thresholds of rats to hindpaw and tail pressure stimulation tested daily throughout at least 3 weeks. When all the measures were pooled, compared to males, female rats had higher thresholds for tail pressure (499 +/- 6 g, n = 188 measures vs. 466 +/- 2 g, n = 144 measures, respectively), but equal thresholds for hindpaw pressure (321 +/- 6 g, n = 188 measures vs. 319 +/- 2 g, n = 144 measures, respectively). Thresholds of female rats in proestrus and estrus were lower than those of rats in metestrus and diestrus for both tail and hindpaw stimulation, whereas those of males did not vary systematically. Thresholds at the two stimulation sites covaried in females but not in males. These results add to the growing list of important interacting factors that underly behavioral sensitivity to noxious somatic stimulation.

Animals↗

PubMed1996

Further evidence for a peripheral component in the enhanced antinociceptive effect of systemic morphine in mononeuropathic rats: involvement of kappa-, but not delta-opioid receptors.

The contribution of a peripheral action of morphine in the augmented antinociceptive effect of this substance was re-evaluated in a well established rat model of peripheral unilateral mononeuropathy (chronic constriction of the common sciatic nerve), using a relatively low dose of systemic morphine (1 mg/kg i.v.) and local low doses of specific antagonists of kappa- (nor-binaltorphimine) or delta-(naltrindole) opioid receptors. Vocalization thresholds to paw pressure were used as a nociceptive test. Escalating doses of nor-binaltorphimine (10-30 micrograms injected locally into the nerve injured paw) significantly and dose dependently reduced the effect of morphine on this paw but not on the contralateral paw, an effect which plateaued at 30 micrograms. By contrast, the local injection of naltrindole (30-40 micrograms into the nerve injured paw) had no effect on morphine analgesia. The doses of opioid receptor antagonists used, injected i.v., in the contralateral paw, or alone in the nerve injured paw had no significant effect. These results suggest that the peripheral effect of systemic morphine in this model of neuropathic pain could be mediated not only by mu- but also by kappa-opioid receptors.

Analgesia↗

PubMed1996

Influence of timing of administration on the analgesic effect of bupivacaine infiltration in carrageenin-injected rats.

BACKGROUND: Recent evidence has suggested that the timing of administration of analgesic drugs could influence their efficacy by reducing the sensitization of the nervous system induced by the nociceptive inputs, but this concept of preemptive analgesia is still debated in both clinical and basic research. METHODS: The model of acute inflammatory pain induced by carrageenin was used to study the influence of timing of administration of bupivacaine (0.2 ml of a 0.5% solution with 0.005 mg/ml epinephrine) on the development of hyperalgesia, edema, and increase in temperature. The animals received bupivacaine 5 min before (BUPI PRE group, n = 20) or 60 min after (BUPI POST group, n = 20) carrageenin (1 ml/kg of 1% solution) was injected into the left hind paw. Two control groups (n = 15 in each) received saline 5 min before or 60 min after administration of carrageenin. Hyperalgesia of the injected paw was evaluated by the vocalization threshold to paw pressure, edema by measuring paw circumference with a thread, and plantar temperature with a thermocouple thermometer. All measurements were done before carrageenin injection then every 30 min thereafter for 240 min. Another series (n = 24), with the same four groups was also evaluated at 24 h. RESULTS: Local injection of bupivacaine 60 min after carrageenin partially reduced the edema and hyperalgesia. The injection of bupivacaine 5 min before carrageenin was more efficient than the delayed injection and reduced hyperalgesia, edema and the increase in temperature temporarily, but did not totally prevent their development. All groups were similar at 240 min and 24 h. CONCLUSIONS: These results show that a slight advantage of infiltration with bupivacaine before injury exists in this carrageenin model of acute inflammatory pain. However, this benefit is limited in time and bupivacaine did not have any preemptive analgesic effect.

Analgesia↗

PubMed1995

Responses of neurons in the caudal intralaminar thalamic complex of the rat to stimulation of the uterus, vagina, cervix, colon and skin.

This study examined responses of 35 neurons in the caudal intralaminar (IL) thalamic nuclei in 12 adult female virgin rats to mechanical stimulation of the skin (brush, pressure, pinch) and to 4 different visceral stimuli (noxious distension of the uterine horns and vaginal canal; gentle distension of the colon and probing the cervix). As in male rats and other species, many IL neurons (24/35) responded to frankly noxious somatic stimuli applied to several bodily regions. Some of these (16/24) also responded to one or more of the visceral stimuli (mainly the noxious ones), while 4/35 responded only to a visceral stimulus. Thus, unlike neurons in lateral thalamus studied under identical conditions, IL neurons appear to be signalling information primarily when intense somatic and visceral stimuli are frankly above the noxious threshold.

Animals↗

PubMed1995

Antinociceptive effect of a kappa-opioid receptor agonist that minimally crosses the blood-brain barrier (ICI 204448) in a rat model of mononeuropathy.

The antinociceptive effect of intraplantar (i.pl.) ICI 204448 ((R,S)-N-[2-(N-methyl-3,4-dichloro-phenylacetamido)-2-(3-carbox yph enyl)- ethyl]pyrrolidine hydrochloride)) (20, 30, 40 and 50 micrograms), a kappa-opioid receptor agonist which has limited access to the central nervous system, was studied in a well-established rat model of peripheral mononeuropathy produced by moderate constriction of the sciatic nerve. Vocalization thresholds to paw pressure were used as a nociceptive test. On the injected nerve-injured paw, ICI 204448 at 20 and 30 micrograms had no significant effect, but higher doses (40 micrograms) produced a significant antinociceptive effect, which plateaued at 50 micrograms. By contrast, no antinociceptive effect was observed on the contralateral paw. The effect of ICI 204448 (40 micrograms) was significantly antagonised by the specific kappa-opioid receptor antagonist nor-binaltorphimine (20 and 30 micrograms), when co-injected in the nerve-injured paw.

Analgesia↗

PubMed1995

Contribution of the sciatic and saphenous nerve to the ventrobasal thalamic neuronal responses to pinch in rats with a chronic sciatic nerve constriction: a study using anesthetic blocks and nerve section.

To extend the study on the respective contribution of the sciatic and saphenous nerve in abnormal nociceptive responses observed in rats with a loose constriction of one sciatic nerve, neuronal responses to pinch applied to the territory of the injured nerve, recorded in the ventrobasal complex of the thalamus have been studied. Eleven neurones recorded in 11 rats with a nerve constriction since 15-19 days and clear abnormal pain-related behaviour to mechanical stimulus, were tested before and during an anesthetic block of the saphenous and/or of the sciatic nerve, and/or after the saphenous nerve section. Only the sciatic nerve block depressed significantly the pinch responses.

Anesthetics↗

PubMed1995

Systemic clonidine differentially modulates the abnormal reactions to mechanical and thermal stimuli in rats with peripheral mononeuropathy.

The antinociceptive action of the systemically administered alpha 2-adrenoceptor agonist clonidine was evaluated in a rat model of peripheral unilateral mononeuropathy produced by loose ligatures around the common sciatic nerve, using nociceptive tests based on mechanical (vocalization threshold to paw pressure) or thermal (struggle latency to paw immersion in a cold (10 degrees C) or hot (44 degrees C) water bath) stimuli. Experiments were performed 2-3 weeks after surgery when pain-related behavior was fully developed. We demonstrated a dissociative action depending on the test used: clonidine (30-100 micrograms/kg i.v.) had a moderate effect on the abnormal reactions to the mechanical stimulus. By contrast it dramatically increased the struggle latency to hot or cold stimuli. These latter effects were completely prevented by prior administration of the alpha 2-adrenoceptor antagonist idazoxan (0.5 mg/kg i.v.).

Adrenergic alpha-Antagonists↗

PubMed1995

Evidence for a peripheral component in the enhanced antinociceptive effect of a low dose of systemic morphine in rats with peripheral mononeuropathy.

In a rat model of peripheral mononeuropathy produced by moderate constriction of the sciatic nerve, we have shown that various i.v. doses of morphine and selective opioid agonists produce potent and long-lasting antinociceptive effects on the vocalization threshold to paw pressure. For all the opioids, the antinociceptive effects were more marked for the paw on the nerve-injured side (nerve-injured paw) than for the sham-operated paw. One contributory mechanism could be a peripheral action of the opioid agonists in the nerve-injured paw. This hypothesis was tested in the present study, using systemic morphine and low doses of local naloxone or its quaternary salt naloxone methiodide, exhibiting peripherally acting antagonist properties. The effects of escalating doses of naloxone (0.5-2 microgram injected i.v. or intraplantar into the nerve-injured paw) or naloxone methiodide (5-30 micrograms into the nerve-injured paw) on the antinociceptive effect of morphine (1 mg/kg i.v.) were evaluated using the vocalization threshold to paw pressure in neuropathic rats at two weeks after placing ligatures, a time when the behavioural pain-related disorders have reached a maximum.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

PubMed1995

Influence of the sympathetic nervous system in the development of abnormal pain-related behaviours in a rat model of neuropathic pain.

This study evaluated the effect of surgical sympathectomy on pain-related behaviours in a well established model of peripheral mononeuropathy produced by loose ligatures around the common sciatic nerve in the rat. Behavioural abnormalities include spontaneous abnormal position of the hindpaw after the nerve constriction, indicative of "spontaneous pain", and changes in responses to mechanical or thermal stimuli applied to this paw. These changes are usually maximal at week 2 after the surgery, stable until weeks 3-4, and disappear between weeks 8 and 12. To assess the role of the sympathetic nervous system in the development and persistence of these abnormalities, four groups of rats were behaviourally tested: (i) rats receiving a complete sham surgery, (ii) rats with a sciatic nerve constriction produced by loose ligatures around the common nerve trunk plus a sham sympathectomy, (iii) rats receiving a lumbar sympathectomy with a sham nerve ligature, and (iv) rats receiving a simultaneous surgical lumbar sympathectomy and a sciatic nerve constriction. The efficacy of the sympathectomy was assessed by the measure of the noradrenaline level in the sciatic nerve. Sympathectomy reduced selectively or even prevented the abnormal reaction to cold temperature and to heat (45 degrees C) in rats with a peripheral mononeuropathy. In contrast, the abnormal reaction to mechanical pressure was not influenced, and the behavioural abnormalities indicating spontaneous pain were still present. Sympathectomy alone resulted in a reduction of the vocalization threshold to pressure on both hindpaws, but also a short-lasting increased tolerance to cold immersion. This study confirms the selective role of the sympathetic nervous system in affecting the development and maintenance of some abnormal pain-related behaviours to thermal stimuli in rats with a moderate, but persistent, constriction of one sciatic nerve.

Animals↗

PubMed1994

Antinociceptive effect of systemic kelatorphan, in mononeuropathic rats, involves different opioid receptor types.

The antinociceptive effect of i.v. kelatorphan (2.5, 5, 10 and 15 mg/kg), a mixed inhibitor of enkephalin degrading enzymes, was studied in a rat model of peripheral unilateral mononeuropathy (chronic constriction of the common sciatic nerve). Kelatorphan at 2.5 and 5 mg/kg had no significant effect on the vocalization threshold to paw pressure test, but higher doses (10 mg/kg) produced a significant antinociceptive effect which plateaued at 15 mg/kg, on both hindpaws. Kelatorphan (10 mg/kg) was co-injected with the specific mu-, delta- and kappa-opioid receptor antagonists naloxone (0.1 mg/kg), naltrindole (1 mg/kg) or nor-binaltorphimine (1 mg/kg). The effect of kelatorphan 10 mg/kg was completely prevented by naloxone, reduced by 75% by naltrindole (both hindpaws), and reduced by 50% by nor-binaltorphimine (contralateral paw only).

Analgesics↗

PubMed1994

[Fundamental mechanisms of pain].

The nervous system structures involved in the transmission to the brain of noxious messages are discussed. In the periphery, receptors termed "nociceptors" consist of both fine unmyelinated and myelinated nerve fibres. The mechanisms of the integration of nociceptive messages at the level of the dorsal horn of the spinal cord and the systems which modulate these messages (segmental, suprasegmental and supraspinal) have also been extensively studied. In addition to the classical pathways, including the spinothalamic and spinoreticular tracts, the modern neuroanatomical techniques, have revealed the existence of unknown pathways. An example of this is the spinoponto-amygdaloid pathway which appears to play a role in the cognitive and affective components of pain. Nowadays numerous strategies are developed for the design of novel analgesics but the major problem for the pharmacologists is the complexity of the nervous system (multiplicity of the receptors, interspecies differences, colocalisations of several transmitters in the same neuron).

Animals↗

PubMed1994

Behavioural pain-related disorders and contribution of the saphenous nerve in crush and chronic constriction injury of the rat sciatic nerve.

This study evaluated the pain-related behaviours induced by 2 models of peripheral sciatic nerve injuries in the rat: transient nerve crush and chronic constriction injury (CCI). Various lesions of the saphenous nerve were performed in order to investigate the role of saphenous innervation in behavioural disorders induced by these nerve injuries. Behavioural testing included assessment of responses to phasic stimulation (mechanical and thermal) and observation of 'spontaneous' pain-related behaviour. Results confirmed that the model of CCI induces marked and prolonged phasic and spontaneous pain-related disorders (up to week 7). Rats with crush injury exhibited moderate and transient hyperalgesia and allodynia to mechanical and thermal stimulation on the lesioned side (with a maximum at day 3 and a recovery by week 1). Section plus ligation of the ipsilateral saphenous nerve on the day of surgery prevented nociceptive behaviours and induced persistent mechanical and thermal anaesthesia or hypoesthesia of the lesioned paw in both models (lasting up to 3-4 weeks). Section without ligation of the saphenous nerve induced comparable results in rats with sciatic crush, but did not significantly modify nociceptive behaviours in rats with CCI. These data emphasise the role of adjacent saphenous nerve in the mechanisms of pain-related disorders induced by these peripheral nerve lesions. On the contralateral paw, pain-related modifications were also observed in both models, suggesting that unilateral nerve lesions induce remote modifications extending beyond the site of the injured nerve.

Animals↗

PubMed1994

Differential action of morphine and various opioid agonists on thermal allodynia and hyperalgesia in mononeuropathic rats.

In a rat model of mononeuropathy produced by 4 loose ligatures around the common sciatic nerve, the effects of 1 mg/kg morphine and mu-, delta- and kappa-agonists, DAMGO (2 and 3 mg/kg), BUBUC (3 and 6 mg/kg) and U-69,593 (1.5 mg/kg), were evaluated by measuring the struggle latency (SL in sec) to immersion of the paw on the nerve-injured side in a cold (10 degrees C) or hot (42 degrees C, 44 degrees C, and 46 degrees C) water bath. Experiments were performed 2 weeks after surgery. The agonists were used at doses that produced potent antinociceptive effects on the vocalization test in this model. At 46 degrees C (clearly in the noxious range), only morphine and DAMGO had significant effects. The effect of morphine lasted for more than 2 h with a maximum at 40 min (SL = 13.8 +/- 1.6 sec, 252% of control values). For 2 and 3 mg/kg DAMGO, the dose-related effect lasted for 120 min at least, with a maximum at 20-40 min (SL = 6.0 +/- 0.5 and 8.8 +/- 0.7 sec, 148% and 170% of control values, respectively). These effects were more potent and prolonged than in normal rats and were reversed by 0.1 mg/kg naloxone i.v. By contrast, morphine and all selective agonists failed to relieve the abnormal reactions to 10 degrees C, 42 degrees C (in the non-noxious range) and 44 degrees C (at the noxious threshold) stimuli. Our data illustrate a differential effect of opioids on nociceptive tests based on different stimulus modalities and intensities in this model of mononeuropathic pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Differential effects of specific delta and kappa opioid receptor antagonists on the bidirectional dose-dependent effect of systemic naloxone in arthritic rats, an experimental model of persistent pain.

In an attempt to determine the opioid receptor class(es) which underly the two opposing effects of naloxone in models of persistent pain, we tested the action of the selective delta antagonist naltrindole, and that of the kappa antagonist MR-2266 on the bidirectional effect of systemic naloxone in arthritic rats. As a nociceptive test, we used the measure of the vocalization thresholds to paw pressure. The antagonists were administered at a dose (1 mg/kg i.v. naltrindole, 0.2 mg/kg i.v. MR-2266), without action per se but which prevents the analgesic effect of the delta agonist DTLET (3 mg/kg, i.v.) or the kappa agonist U-69,593 (1.5 mg/kg, i.v.) respectively, and does not influence the effect of morphine (1 mg/kg i.v.) or the mu agonist DAMGO (2 mg/kg, i.v.) in these animals. In arthritic rats injected with the delta antagonist, the paradoxical antinociceptive effect produced by 3 micrograms/kg i.v. naloxone was not significantly modified (maximal vocalization thresholds (% of control) were 146 +/- 9% versus 161 +/- 7% in the control group). By contrast, the hyperalgesic effect produced by 1 mg/kg i.v. naloxone was significantly reduced (maximal vocalization thresholds were 87 +/- 4% versus 69 +/- 5% in the control group). In rats injected with the kappa antagonist, the antinociceptive effect of the low dose of naloxone was almost abolished (mean vocalization thresholds were 115 +/- 3% versus 169 +/- 7%) whereas the hyperalgesic effect of naloxone 1 mg/kg i.v. was not significantly modified (mean vocalization thresholds = 70 +/- 3% and 65 +/- 3%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1993

Antinociceptive effect of systemic PC 12, a prodrug mixed inhibitor of enkephalin-degrading enzymes, in normal and arthritic rats.

The antinociceptive effects of various i.v. doses (2.5, 3.75, 5, 10, 15 and 20 mg/kg) of a prodrug mixed inhibitor of enkephalin degrading enzymes, PC 12, were tested in normal and Freund's adjuvant-induced arthritic rats, using vocalization thresholds to paw pressure as a nociceptive test. In normal animals, PC 12 produced a dose-dependent antinociceptive effect over the 2.5-15 mg/kg range, but the time-course of the response was shorter with the dose of 20 mg/kg. In arthritic rats, PC 12 had no significant effect at 2.5 mg/kg, but induced a highly significant dose-dependent antinociceptive action with 3.5 and 5 mg/kg, which decreased with the highest doses. The antinociceptive effect of PC 12 (10 mg/kg i.v.) was prevented by naloxone (0.5 mg/kg i.v.) in the two categories of rats, providing evidence for the involvement of opioid receptors. These results are discussed in relation with the increased level of endogenous opioid substances in the spinal dorsal horn of arthritic rats and the nociceptive test used.

Aminopeptidases↗

PubMed1993

Responses of neurons in thalamic ventrobasal complex of rats to graded distension of uterus and vagina and to uterine suprafusion with bradykinin and prostaglandin F2 alpha.

This study examined the responses of somatic-responsive neurons in and near the ventrobasal complex (VB) of halothane/nitrous oxide-anesthetized and paralyzed estrous virgin rats to increasing levels of distension of the uterine horn and vaginal canal and to uterine suprafusion with PGF2 alpha and bradykinin (BK). While individual responses of single neurons to uterine and vaginal distensions were idiosyncratic, as a group the neurons responded in a graded fashion to graded distensions, producing stimulus-responses functions nearly identical to those produced by conscious rats making escape responses to the same stimuli [Berkley and Wood, Soc. Neurosci, Abstr., 15 (1989) 979; Berkley et al., Soc. Neurosci. Abstr., 16 (1990) 416]. In addition, most neurons responded vigorously to PGF2 alpha and BK, with responses to BK but not PGF2 alpha, reliably preceding the 'giant' uterine contractions that were also produced by these algogenic agents. These results indicate that certain neurons in and near VB may as a group be involved in some aspect of pain arising from female reproductive organs. The responses of these neurons to somatic and possibly other visceral stimuli, however, point to their potential additional involvement in other aspects of visceral and somatic nociception.

Animals↗

PubMed1993

The highly selective delta agonist BUBU induces an analgesic effect in normal and arthritic rat and this action is not affected by repeated administration of low doses of morphine.

The effect of various doses of the selective delta agonist BUBU (Tyr-D-Ser(O-t-butyl)-Gly-Phe-Leu-Thr(O-t-butyl) on the vocalization threshold to paw pressure were compared in normal and arthritic rats, a suitable clinical model of chronic pain. In both group of rats, the intravenous administration of BUBU (6, 9, 12 mg/kg in normal and 1.5, 3, 6 mg/kg in arthritic rats) led to significant antinociceptive effects. The same dose of BUBU (6 mg/kg i.v.) produced a much more potent antinociceptive effect in arthritic than in normal rats, and a dose as low as 1.5 mg/kg produced a significant analgesic effect in the arthritic animal, whereas at 3 mg/kg BUBU was ineffective in normal rats. The analgesic effects of BUBU (9 mg/kg in normal and 3 mg/kg in arthritic rats) were completely prevented by the selective delta antagonist naltrindole (1 mg/kg i.v. a dose devoid of analgesic potency per se), while they were not affected by the selective mu antagonist naloxone (0.05 mg/kg i.v.). In addition, 3 mg/kg i.v. of BUBU remained effective in morphine tolerant arthritic rats. These results suggest that delta opioid receptor activation can modulate the transmission of cutaneous mechanical nociceptive information in rats, especially in inflammatory pain conditions.

Analgesics↗