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D Ardid

Publications and source records attributed to D Ardid.

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

Analysis of ultrasonic vocalisation does not allow chronic pain to be evaluated in rats.

Most pain tests used for the assessment of drug analgesic activity in animal chronic pain models are based on the measurement of the response to an external acute stimulation (thermal, mechanical or electrical). But these stimuli are not related to the chronic pain experienced by the animal. Quantitative analysis of the spontaneous behaviour induced by the chronic pain state is needed. Several authors have suggested that ultrasonic vocalisations (USVs) emitted by rats in painful situations might reflect expression of affective pain. In a first study, we recorded spontaneous USVs in sub-chronic and chronic pain models: inflammation induced by carrageenan, arthritis induced by Freund's adjuvant and diabetes induced by streptozotocin. The USVs were analysed when naive Sprague-Dawley rats were alone and during non-agonistic interaction with a conspecific. When the rats were alone they did not emit any USV. During social interaction, no difference in either the frequency or the duration was observed between the emissions of healthy rats and rats in pain. In a third study, the influence of three parameters, degree of confrontation between the rats, age of the conspecific and housing conditions (isolated or collective) was studied in the arthritic rat model. Arthritic rats did not emit more USVs than controls in any of our experimental conditions. A fourth study showed that Aspirin (200 mg/kg) had no effect on the USVs, this data confirms the lack of direct relationship between USVs and experimental chronic pain in rats in our conditions.

Analgesics↗
PubMed2002

Short-chain fatty acid enemas fail to decrease colonic hypersensitivity and inflammation in TNBS-induced colonic inflammation in rats.

BACKGROUND AND AIMS: Short-chain fatty acid (SCFA) (especially butyrate) enemas are widely used to reduce symptoms associated with human inflammatory bowel disease. The purpose of this study was to evaluate their real effect on colonic sensitivity in rats. METHODS: The effects of saline and SCFA enemas (acetate, propionate and particularly butyrate) were studied on visceral pain thresholds following colonic distension in control rats and in rats with colitis (instilled with trinitrobenzene sulfonic acid (TNBS)). RESULTS: Butyrate enemas (40 mM twice daily for 14 days) decreased colonic pain thresholds in control rats; they did not reduce the TNBS-induced hypersensitivity, but on the contrary increased its duration (without modifying the inflammation score). This pronociceptive effect was confirmed in control rats receiving twice daily enemas of 80 mM for 3 days and two enemas of 240 mM of a butyrate solution. The other SCFA enemas did not modify the hypersensitivity of rats with colitis and induced proinflammatory effects. CONCLUSIONS: The beneficial effect of SCFA (especially butyrate) enemas on hypersensitivity and inflammation in inflammatory bowel disease is questionable and needs to be thoroughly investigated in humans.

Acetates↗
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

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

Potentiation of morphine and clomipramine analgesia by cholecystokinin -B antagonist CI-988 in diabetic rats.

The aim of this study was to determine the influence of an intrathecally injected cholecystokinin-B (CCK-B) receptor antagonist, CI-988, on the analgesic effect of morphine and clomipramine in diabetic rats. Administered alone, morphine (0.1 mg/kg, i.v.) and clomipramine (3 mg/kg, i.v.) have respectively no effect and only a slight effect on vocalization thresholds to paw pressure in diabetic rats, but, when coadministered with CI-988 (0.1 microg/rat, i.t.), an appreciable antinociceptive effect was observed. This suggests that a spinal blockade of cholecystokininergic system increases the analgesia induced by morphine or clomipramine. A CCK-B receptor antagonist could thus be used to lower dosages of morphine or antidepressant drugs in the management of neuropathic pain in humans, and thereby reduce their side effects.

Analgesia↗
PubMed1999

Amygdala lesions produce analgesia in a novel, ethologically relevant acute pain test.

Acute pain tests using mechanical stimuli typically do not involve objects important in the evolutionary history of the subjects, and may fail to evaluate the contribution of biobehavioral defensive reactions to the total pain response. Spines are common structural defenses that protect plants and animals against predation. The present studies examined the reaction to contact with such natural, mechanical pain stimuli in the laboratory rat, utilizing a floor board with protruding pins located in the middle of a novel alley (the "fakir" test). Behavioral responses were characterized in 10-min tests (Experiment 1). Subjects showed voluntary contact with the pins followed by patterns of avoidance and risk assessment (stretch attend and stretch approach). Few subjects crossed the array of pins. The amygdala has been implicated in the perception of pain, particularly in stressful or fearful contexts. In Experiment 2, the fakir test was used to examine, concurrently, the effects of amygdala lesions on analgesiometric (frequency and duration of pin crossings) and anxiometric (risk assessment) measures. Large, bilateral, lesions of the amygdala significantly increased both the number of pin crossings and time spent on the pins without affecting the risk assessment measures. These findings suggest a possible dissociation between anxiety and pain perception with an important (nonaffective) role for the amygdala in the latter.

Amygdala↗
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

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↗
PubMed1994

Evidence for a central long-lasting antinociceptive effect of vapreotide, an analog of somatostatin, involving an opioidergic mechanism.

The antinociceptive effect of the octapeptide vapreotide, an analog of somatostatin, was studied after systemic injection in normal mice using the hot plate and abdominal stretching assays, and in normal rats using the paw pressure analgesiometric assay. Vapreotide was ineffective at 1 microgram/kg s.c. in the hot plate test in mice, but 30 min after injection it induced an antinociceptive effect at s.c. injected doses of 8, 64, 512 and 4096 micrograms/kg, with an ED50 of 213 +/- 5 micrograms/kg. For the three highest doses this effect persisted 24 hr after the injection (maximal increase: +80 +/- 23% for 512 micrograms/kg) and disappeared at 48 hr. In the phenylbenzoquinone stretching test, in mice, the ED50 was 186 +/- 6 micrograms/kg (maximal decrease: -63 +/- 5%); the effect persisted 24 hr only for the same two highest doses. Using the paw pressure test, in rats, a dose-dependent increase in paw withdrawal and vocalization thresholds was observed for 21 and 24 hr, respectively, after s.c. injections of 16, 64 and 512 micrograms/kg. Global scores obtained for vocalization thresholds were significantly increased (vs. paw withdrawal thresholds) for 64 and 512 micrograms/kg. Carrageenan-induced nociception in rats was reduced for 21 hr by 64 and 512 micrograms/kg s.c.; scores of the contralateral noninflamed paw were also increased. Vapreotide administered locally in the inflamed paw was inactive. No change in edema volume was obtained after systemic injection of vapreotide.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Vocalization elicited by activation of A delta- and C-fibres in the rat.

Complex vocal responses in both the audible and ultrasonic frequency ranges were elicited by a single 2 ms electrical pulse applied to the tail. The first two cries exhibited consistent latencies and durations, were intensity-dependent and were triggered by peripheral fibres with conduction velocities of 7.3 +/- 0.8 and 0.7 +/- 0.1 ms-1, respectively. These behavioural responses are reminiscent of first and second pain triggered by A delta- and C-peripheral fibres in humans. They were followed by irregular audible cries with a fundamental frequency of 1.5 kHz and '22 kHz ultrasonic calls'.

Animals↗
PubMed1993

Are mechanical and cold allodynia in mononeuropathic and arthritic rats relieved by systemic treatment with calcitonin or guanethidine?

The putative antinociceptive action of guanethidine and calcitonin systemically injected has been compared in 2 rat models of persistent experimental pain: Freund's adjuvant-induced arthritis (n = 29) and mononeuropathy induced by 4 loose ligatures around the sciatic nerve (n = 24). Guanethidine (30 mg/kg, i.v.) and calcitonin (0.125 mg, s.c.) were injected once a day over 1 week, when hyperalgesia was fully developed. The antinociceptive action was gauged using nociceptive tests based on mechanical or cold stimuli (vocalization threshold to paw pressure and struggle latency to 10 degrees C, respectively), and the score of spontaneous pain-related behavior was measured on the basis of the abnormal hind paw position. No antinociceptive action was observed in calcitonin-compared to saline-injected rats, either in arthritic or neuropathic animals. Guanethidine treatment was ineffective on hyperalgesia exhibited in arthritic rats but was able to reduce reliably and even suppress the abnormal reactions to cold stimulus in neuropathic animals. The lack of hypoalgesic action of calcitonin versus its beneficial action in bone repair, as well as the possible role(s) of the sympathetic system in neuropathic versus arthritic pain and in hyperalgesia versus physical signs of inflammation, are discussed.

Animals↗
PubMed1992

High-performance liquid chromatographic determination of amitriptyline and its main metabolites using a silica column with reversed-phase eluent. Application in mice.

A method was developed for the assay of amitriptyline, amitriptyline N-oxide, nortriptyline, desmethylnortriptyline and E (trans) and Z (cis) isomers of 10-hydroxyamitriptyline and of 10-hydroxynortriptyline in plasma and brain of animals, using high-performance liquid chromatography with ultraviolet detection (254 nm). Single extraction was performed at pH 10.5 from 0.25 ml of plasma or 1 ml of brain mixture. Chromatographic separations were achieved with a silica column and an aqueous methanol mobile phase containing ammonia. This procedure offers high sensitivity (8-10 ng/ml), high linearity (r > 0.99) and acceptable precision (coefficient of variation < or = 13.3%). The method was used to determine levels of amitriptyline and its major metabolites in mice 30 min after a single intraperitoneal administration of amitriptyline (20 mg/kg).

Amitriptyline↗
PubMed1992

Antinociceptive effects of acute and 'chronic' injections of tricyclic antidepressant drugs in a new model of mononeuropathy in rats.

The tricyclic antidepressant drugs (TCAs) are commonly used in the treatment of chronic, especially neuropathic, pain. We evaluated their possible effect on a new model of neuropathic pain-related behaviour induced by ligatures tied loosely around the common sciatic nerve. The effects of 3 TCAs with different monoaminergic spectra (clomipramine, amitriptyline and desipramine) were assessed 2 weeks after surgery, the time of the maximum hyperalgesia, on a 'phasic' test (vocalization threshold to paw pressure) and on a 'tonic' test (score of the spontaneous pain-related behaviour). TCAs were acutely (0.5 and 2 mg/kg, i.v.) and 'chronically' injected (7 injections, once every half-life of the drug: 0.75 and 1.5 mg/kg, s.c., for clomipramine and 1.5 and 3 mg/kg, s.c., for amitriptyline and desipramine). Acutely injected clomipramine and amitriptyline (0.5 mg/kg, i.v.) and desipramine (2 mg/kg, i.v.) showed an antinociceptive naloxone-reversible effect, assessed by an increase in the vocalization threshold to the paw pressure test and, for amitriptyline, by a decrease in tonic pain scores. Chronically injected TCAs induced a significant and progressive increase in the vocalization threshold with a time course parallel to that of their suspected plasma or nerve tissue levels: (i) a regular increase of scores for the first 3-4 injections, (ii) then a plateau until the last injection, and (iii) a progressive decrease with a dose-dependent duration of the effect, longer than that obtained with a corresponding acute dose. This study showed that in this new model of mononeuropathy, acutely and chronically injected TCAs induce an antinociceptive effect and suggested that their analgesic action could be related to the monoaminergic spectrum of the drug in relation to the opiate systems.

Animals↗