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Biomedical subjects

D Jourdan

Publications and source records attributed to D Jourdan.

At least 19 recordsLinked to original sources
PubMed2003

Evidence for an involvement of supraspinal delta- and spinal mu-opioid receptors in the antihyperalgesic effect of chronically administered clomipramine in mononeuropathic rats.

The mechanisms of involvement of the opioidergic system in the antinociceptive effect of antidepressants remain to be elucidated. The present study was designed to determine what type of opioid receptors may be involved at the spinal and supraspinal levels in the antihyperalgesic effect of clomipramine, a tricyclic antidepressant commonly prescribed in the treatment of neuropathic pain. Its antihyperalgesic effect on mechanical hyperalgesia (paw pressure test) in rats induced by chronic constriction injury of the sciatic nerve was assessed after repeated administrations (five injections every half-life, a regimen close to clinical use). Naloxone administered at a dose of 1 mg/kg i.v., which blocks all opioid receptors, or at a low dose of 1 microg/kg i.v., which selectively blocks the mu-opioid receptor, inhibited the anti-hyperalgesic effect of clomipramine and hence indicated that mu-opioid receptor is involved. Depending on whether they are administered by the intracerebroventricular or intrathecal route, specific antagonists of the various opioid receptor subtypes [D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-ThrNH2 (CTOP), mu; naltrindole (NTI), delta; and nor-binaltorphimine (nor-BNI), kappa] differently modify the antihyperalgesic effect of chronically injected clomipramine. The effect was inhibited by intrathecal administration of CTOP and intracerebroventricular administration of naltrindole, whereas nor-BNI was ineffective whatever the route of injection. These results demonstrate a differential involvement of opioid receptors according to the level of the central nervous system: delta-receptors at the supraspinal level and mu-receptors at the spinal level. Clomipramine could act via a neuronal pathway in which these two receptors are needed.

Animals↗
PubMed2002

Old as mature LOU/c/jall rats enhance protein selection in response to a protein deprivation.

Previous experiments have shown a strong decrease in protein consumption as rats grow old. This result could be induced by an impaired regulation of feeding behaviour. Present study investigated the ability of ageing rats to adapt their protein intake to protein requirements. Four groups of self-selecting LOU/c/jall male and female rats (4, 16, 22, 28 months at the beginning of the experiments) were submitted to 4-days of protein deprivation periods while their macronutrient intakes were monitored. Moreover, they were submitted to a 4-day fasting period. After reintroduction of proteins, old and senescent rats were able to increase their protein intake in response to the specific protein need created by the protein deprivation. They were also able to increase caloric intake after the fasting period. These results led to the conclusion that the loss of appetite for protein observed with ageing reflects rather an adaptation than an impairment of the regulation of macronutrient choice. Another important observation was that older animals did not recover initial body weight after a body weight loss even if they ate as many calories as younger animals. This data supports a decrease in the efficacious utilization of body fuels in old and senescent rats.

Adaptation, Physiological↗
PubMed2002

[School health education: practices and representations of primary school teachers].

A better understanding of primary school teachers' practices and representations toward health education (HE), and identification of individual or structural resistance as well as the partnership and training needs all constitute important goals in HE research. A quantitative study was conducted between April and December 2001 on a representative sample of the population of primary school teachers (n = 673) in the Auvergne region. The results demonstrate that the majority of teachers declare practicing and implementing HE. The approach is primarily thematic, essentially limited to a few lessons since it is only integrated into a broader project 20% of the time. 30% of teachers work in partnership, mainly with partners in school health; however, parents are rarely involved in HE activities. Parameters which influence the teachers' practices and representations are: (1) prioritizing work within an educational network and an inter-communal pedagogical regrouping, with the advantage that there are a greater number of teachers to do HE in these schools than in others, and (2) receiving initial or in-service training. These results suggest that a policy aiming to generalize the inclusion of HE in French primary schools must develop teacher training as well as support and accompany the collective dynamics within schools.

Attitude↗
PubMed2001

Effects of rapid eye movement (REM) sleep deprivation on pain sensitivity in the rat.

The relationship between pain and sleep seems to be reciprocal: if pain may interrupt or disturb sleep, poor sleep can also influence pain perception. However the influence of sleep disturbances on pain sensitivity remain poorly investigated. The aim of this study was to assess the effect of REM sleep deprivation on the reaction of rats subjected to different noxious stimuli. In each experiment 16 Wistar male rats were randomly assigned to two groups: controls (n=8), and REM sleep deprived rats (n=8). REM sleep deprivation was elicited using the 'inverted flower pot' technique. Four different experiments were performed to assess the sensitivity to mechanical (vocalization threshold in paw pressure), thermal (tail withdrawal latency in hot water immersion), electrical (envelope of 2nd peep in tail shock test) and chemical (analgesic behavior in formalin test) noxious stimuli. All experiments were performed over a 5-day period with baseline (day 1, day 2) in a dry environment and REM sleep deprivation (day 3, day 4 and day 5) in a wet environment. Under wet conditions, vocalization threshold in the paw pressure test (-20%, P=0.005), and tail withdrawal latency in the hot water immersion test (-21%, P=0.006) were significantly lower, and the envelope of 2nd peep in the tail electrical shock was significantly greater (+78%, P=0.009), in REM sleep deprived rats compared to controls. However, under wet conditions the mean duration of nociceptive behaviors in the formalin test did not differ between the two groups. In conclusion, REM sleep deprivation induces a significant increase in the behavioral responses to noxious mechanical, thermal and electrical stimuli in rats.

Animals↗
PubMed2001

[Impact of age on pain perception and analgesic pharmacology].

INFLUENCE OF AGING ON PAIN: Although pain affects a large majority of the elderly population living in the community and in institutions, our knowledge of the evolution of pain experience with age is poor. Results of clinical surveys and experimental pain studies are contradictory, showing no change, an increase, or a decrease of pain with age. Many results suggest a decrease of pain perception with age that could be explained by peripheral and central neuroanatomical aging and psychological changes of the aging patient towards pain. INFLUENCE OF AGE ON THE PHARMACOLOGY OF ANALGESICS: Biological aging added to multiple pathologies and polymedication explains the pharmacological changes of analgesics. Among pharmacokinetic changes that are globally well known, vigilance must focus on renal excretion of analgesics and their metabolites and on the increased risk of side-effects and drug interactions. Information on pharmacodynamic changes of analgesics are scarce in aging patients who are susceptible to drugs and which demographical trend increases. PERSPECTIVES: A better fundamental knowledge of the evolution of pain with age could help to improve care in the elderly with pain, especially in very old subjects with cognitive impairment and loss of communication skills, where pain evaluation is particularly difficult. Also, more research is needed on the pharmacodynamics of analgesics in older subjects, with a view of a decreased iatrogenic risk, a better pain treatment and quality of life of the elderly.

Age Factors↗
PubMed2001

Automated behavioural analysis in animal pain studies.

The assessment of the effectiveness of analgesics is strongly based on observational data from behavioural tests. These tests are interesting and give a quantification of the effect of the drugs on the whole animal but their use is subject to several difficulties: (i) many results are difficult to analyse as they only correspond to the evaluation of a reflex response; (ii) the tests dealing with more integrated responses are also more difficult to use and closely depend on the experimenter's subjectivity. If automation is widely used in a lot of research fields, this is not the case in behavioural pharmacology. Yet, it can contribute to optimize the tests. The use of signal processing devices allows the automated (and thus objective) measurement of behavioural reactions to nociceptive stimulation (amplitude of a reflex, vocal emission intensity). Mechanical devices based on a computer-driven dynamic force detector allows the recording of some pain behaviours. Video image analysis allows the quantification of more complex behaviours (nociception-induced specific motor behaviours) as well as meaningful information during the same experimentation (exploratory behaviour, total motor activity, feeding behaviour). Moreover, these methods make it possible to obtain a more objective measurement, to reduce animal-experimenter interactions, to ease system use, and to improve effectiveness. The prospects to work in this field are multiple: continuation of the attempts at an automation of the behaviours specifically induced by chronic pain; development of real animal pain monitoring based on analysis of specific and non-specific behavioural modifications induced by pain. In this context, the automation of the behavioural analysis is likely to make possible real ethical progress thanks to an increase in the test's effectiveness and a real taking into account of animal's pain. Nevertheless, there are some limits due to characteristics of the behavioural expression of nociception and technological problems.

Animals↗
PubMed2001

Effect of morphine on caloric intake and macronutrient selection in male and female Lou/c/jall rats during ageing.

Previous studies have showed a shift of preferences from carbohydrate to fat in the Lou/c/jall rat with advancing age when they are submitted to a self-selection procedure. Protein intake also decreased according to the age, earlier for males (after 16 months) than for females (29 months). The present study aimed at investigating the mechanism underlying these modifications. We analysed the effect of the reference mu agonist, morphine (5 mg/kg subcutaneous), on the caloric intake, body weight and macronutrient intake of 30 male and 30 female rats divided in four age groups: young adults (10), mature (17), old (24) and senescent rats (29 months). During the experiment, animals had the choice between separate sources of the three pure macronutrients. Morphine injection reduced total daily caloric intake and induced a decrease in body weight. The weight loss was age- and sex-related (males and old rats were more affected by the drugs). The injection of morphine evoked a triphasic influence on the chronology of the intake. A brief (1 h) hypophagia was followed by an hyperphagia (3 h) and a persistent hypophagia (8 h). No modification in the diet composition was observed. These results did not support a clear involvement of the opioid system concerning the modifications in macronutrient rates in diet previously observed across ageing.

Aging↗
PubMed2001

Potentiation of the antinociceptive effect of clomipramine by a 5-ht(1A) antagonist in neuropathic pain in rats.

The benefit of antidepressant treatment in human neuropathic pain is now well documented, but the effect is limited and slow to appear. It has been demonstrated that the association of a 5-HT(1A) antagonist and a serotoninergic antidepressant reduced the delay of action and increases the thymoanaleptic effect of the drug. The purpose of this work was to evaluate the combination of an antidepressant and a 5-HT(1A) antagonist in animal models of chronic neuropathic pain. We studied the antinociceptive effect of the co-administration of clomipramine and a 5-HT(1A) antagonist (WAY 100,635) in a pain test applied in normal rats and in two models of neurogenic sustained pain (mononeuropathic and diabetic rats). The results show an increase in the antinociceptive effect of acutely injected clomipramine due to WAY 100,635 in these models, which is majored when the two drugs are repeatedly injected. The 5-HT(1A) antagonist reduced the delay of onset and increased the maximal antinociceptive effect of clomipramine. These new findings argue for using the combination of an antidepressant and a 5-HT(1A) antagonist in human neuropathic pain therapy.

Animals↗
PubMed2000

Age-related changes in nociception and effect of morphine in the Lou rat.

Little is known about how the ageing process affects pain sensitivity and a relevant animal model is therefore required. The effect of age on pain reactivity in animals has been investigated by several experimenters but the results are conflicting. Four groups of male and female Lou/C/Jall rats (4-29 months old) were used for our study. Four pain tests based on evaluation of reflex or more integrated behaviours after a thermal (tail immersion test) or mechanical (paw pressure test and von Frey test) stimulation were used. With mechanical stimulus, a significant decrease in the pain threshold across age was observed, females were more sensitive than males. This increase in nociceptive sensitivity to mechanical stimulation was more pronounced on integrated behaviours (struggle reaction) than on withdrawal reflex. An age-related increase in sensitivity was found on von Frey test. No effect on the latency of reflex induced by thermal stimulation was observed. In addition, a decrease in the spontaneous motor activity during exploration was observed across ageing; this effect was more marked for the females. The effect of morphine at doses of 1, 3 and 9 mg/kg (s.c.) decreased in intensity across ageing. These data demonstrate the need to use (1) various noxious stimuli because differences were observed in the modification of pain reactivity according to the nature of the stimulus; (2) various pain parameters and particularly integrated behaviours; (3) several age groups. In addition, Lou/C/Jall rat could be a useful model for studying of effect of age on pain.

Aging↗
PubMed1999

Pharmacological validation of an automated method of pain scoring in the formalin test in rats.

In 1997, we described a new automated method of scoring the pain behaviors in the formalin test. The algic behavior was automatically measured with the help of a video-analysis system. The time during which the animal grooms, licks, or bites itself was used as the parameter of pain. In the present study, we tested various analgesics to realize a pharmacological validation of the system. The effect of opiate analgesic (morphine, i.v.), nonsteroidal anti-inflammatory drugs (paracetamol, i.v., piroxicam, i.v., indomethacin, i.v.), antidepressant drugs (clomipramine, desipramine, nortryptyline, and paroxetine, i.p.), and serotonin (i.t.) were analyzed. A dose of 1.25 mg/kg of morphine induced a decrease in the scores of phases 1 and 2. Naloxone (0.25 mg/kg) reversed the effect of morphine (2.5 mg/kg). A 20-mg/kg dose of indomethacin induced a decrease in the second phase, and paracetamol induced a decrease in both phases (analgesic doses were 400 mg/kg and 200 mg/kg for first and second phases, respectively). Piroxicam had no effect on the pain scores. Clomipramine, desipramine, and paroxetine at a dose of 5 mg/kg induced a significant decrease in the second phase. Nortriptyline had no effect on the pain scores. A dose of 75 microg of serotonin induced a decrease in both phases 1 and 2. This study demonstrated that this system shows a good pharmacological sensitivity, although it is lower than that of manual assessment.

Analgesics↗
PubMed1998

Effect of analgesics on audible and ultrasonic pain-induced vocalization in the rat.

Brief electrical pulses applied to the rat tail elicit a complex vocal response which includes audible (peeps, chatters) and ultrasonic (USV) components. Aspirin and amitriptyline had no effect on the vocal responses. Morphine showed a dose-dependent and naloxone reversible antinociceptive effect on the 1st and 2nd audible peeps by decreasing their intensity (evaluated by their envelopes which correspond to the outer bounds of the soundwave amplitude plotted as a function of time), with ED50 values of 1.96 mg/kg and 0.36 mg/kg i.v. respectively. Paracetamol significantly reduced only the intensity of the second peep at the dose of 200 mg/kg iv. Chatter intensity was decreased by doses of 1 and 3 mg/kg i.v. of morphine which would suggest an effect on emotional components of pain. The intensity of USV was affected by morphine injection although the variations observed were non-significant. These data clearly implicate a specific role for the opioid analgesics in modifying the vocal pain related behaviors.

Amitriptyline↗
PubMed1997

Differential influence of two serotonin 5-HT3 receptor antagonists on spinal serotonin-induced analgesia in rats.

We tested the antinociceptive effect of intrathecal (i.t.) administration of 5-HT3 and the 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide (mCPBG), in rats submitted to a mechanical noxious stimulus and the influence of the 5-HT3 receptor selective antagonists, tropisetron and granisetron. Both 5-HT and mCPBG (0.01, 0.1, 1, 10, 20 micrograms/rat) produced a significant dose-dependent antinociception. The lowest active doses were 0.1 and 1 microgram for 5-HT and mCPBG, respectively. The effect, observed with 20 micrograms, was significantly lower with mCPBG (+33 +/- 6%) than with 5-HT (+63 +/- 7%). For 5-HT-induced antinociception, the minimal inhibitory doses were 0.001 micrograms/rat for tropisetron and 10 micrograms/rat for granisetron. In contrast, the same doses of the two antagonists (from 0.1 microgram/rat) similarly inhibited the effect of mCPBG. This study provides evidence that contrary to tropisetron, doses of granisetron able to inhibit the effect of a 5-HT3 receptor agonist failed to reduce that of 5-HT. This demonstrates a heterogeneity between 5-HT3 receptor antagonists and questions the true involvement of these receptors in spinal 5-HT-induced antinociception.

Animals↗
PubMed1997

A new automated method of pain scoring in the formalin test in rats.

The formalin test is a valuable tool widely used in animal pain studies. We offer a new automated technique based on continuous recording of movements of animals injected in a hindpaw with formalin (5%). This method, based on image processing, allows the discrimination of specific pain-induced behaviors and general motor activity. The comparison of the pain scores evaluated by manual and automated methods showed the same biphasic response. This new process was validated by using compounds known to alter pain responses to formalin: morphine and a non-steroidal anti-inflammatory drug (ketoprofen). Morphine dose-dependently usually affects the two phases of formalin response with ED50 of 2.0 +/- 0.5 and 1.5 +/- 0.5 mg/kg s.c. for the first and the second phase, respectively. The injection of ketoprofen significantly decreased pain scores of the second phase but not those of the first phase. The specificity of the method was studied by determining the effect of diazepam. This sedative compound induced a decrease in pain scores as well as a decrease in motor activity parameters. These data show that this automated technique can be considered as a relevant, sensitive and specific tool which allows the easier use of the formalin test especially for the screening of analgesic drugs.

Analgesics, Opioid↗
PubMed1997

Audible and ultrasonic vocalization elicited by a nociceptive stimulus in rat: relationship with respiration.

Brief electrical pulses applied to a rat's tail elicit complex vocal responses including audible ("peeps," "chatters") and ultrasonic components. These responses, particularly the two first peeps which have been shown to be triggered by A delta- and C-fibers, could provide a useful tool in pain studies. In the present study, we aimed to optimize this test by investigating the influence of respiration on the vocal responses. The following results were obtained: 1) As expected, the vocalization periods were concomitant with expiration; 2) The phase of the respiratory cycle at the onset of stimulation did not modify the mean intensities of the peeps; 3) The lung volume at the onset of stimulation significantly influenced the intensity and duration of the first peep and the latency of the second peep. Taking account of respiratory parameters in pain tests based on a quantified analysis of vocal responses could improve their sensibility by reducing variability and their specificity by detecting confounding factors such as effects of drugs on respiratory centres or on motor function.

Animals↗
PubMed1995

Involvement of bulbospinal pathways in the antinociceptive effect of clomipramine in the rat.

The involvement of bulbospinal pathways in the antinociceptive effect of clomipramine in experimental pain was studied. The antinociceptive effect of the antidepressant (0.5 mg/kg), intravenously injected, was evaluated after a unilateral lesion of the dorsolateral funiculus. The results showed that this effect was suppressed only in the hindpaw ipsilateral to the dorsolateral funiculus lesion, and suggest that the antinociceptive effect of antidepressants needs intact descending inhibitory bulbospinal pathways.

Analgesics↗
PubMed1995

Audible and ultrasonic vocalization elicited by single electrical nociceptive stimuli to the tail in the rat.

We describe audible and ultrasonic vocalization elicited in rats by a short electrical pulse applied to the tail. Three types of vocal emissions were recorded: (1) 'peep', characterized by a repartition of energy over a wide range (0-50 kHz) of frequencies without any clear structure; (2) 'chatters', characterized by an audible (frequencies in hearing range of humans) fundamental frequency (2.47 +/- 0.03 kHz) and harmonics; and (3) 'ultrasonic emissions', characterized by a succession of slightly modulated pulses with frequencies in the 20-35 kHz range. Peeps and chatters were never recorded before the application of the stimuli. Several different vocalization patterns were described in terms of these types of responses. Just after the stimulation, all the animals emitted a 1st peep, which was generally (61%) followed by a 2nd one. They appeared with reproducible latencies, durations and envelopes. The envelopes of the audible (peeps and chatters) responses were intensity-dependent. Experimental data (moving the stimulation site, lidocaine injection) indicated that the 1st and 2nd peeps were triggered by two different groups of peripheral fibres with mean conduction velocities of 7.3 +/- 0.8 and 0.7 +/- 0.1 m/sec, respectively. This suggested an involvement of A delta and C fibres. Morphine showed a naloxone-reversible and dose-dependent antinociceptive effect by decreasing the 1st and 2nd peep envelopes. It is concluded that a short stimulus applied to the tail triggers a complex behavioural repertoire. It is proposed that this model will be a useful tool for physiological and pharmacological studies of nociception.

Anesthetics, Local↗