Biomedical subjects

A Eschalier

Publications and source records attributed to A Eschalier.

At least 55 records · Page 3Linked to original sources

PubMed1999

Simultaneous analysis of ketamine and bupivacaine in plasma by high-performance liquid chromatography.

A reversed-phase HPLC technique for the simultaneous measurement of both bupivacaine and ketamine in plasma is described. Plasma samples (0.5 ml) were prepared using a rapid and simple back-extraction technique. Resolution of both analytes and the internal standard, desipramine, from medicines coadministered to surgical paediatric patients was obtained using a 5 microm cyano (CN) (250x4.6 mm) column and a mobile phase comprising methanol-acetonitrile-orthophosphoric acid-0.01 M sodium dihydrogenphosphate (200:80:2:718). Good sensitivity for both analytes was observed using UV detection at a wavelength of 215 nm. The method has been validated according to the criteria established by the Journal of Chromatography B.

Bupivacaine↗

PubMed1999

Pain related behaviour during vincristine-induced neuropathy in rats.

The development of suitable animal models of neuropathic pain is essential to understand the pathophysiological mechanisms responsible for this condition. This study presents the alterations in nociception observed in rats suffering from a peripheral neuropathy induced by 10 daily repeated intravenous injections of vincristine at doses of 50 or 75 microg/kg (total dose 500 or 750 microg/ kg). The rats present both mechanical hyperalgesia, allodynia and a loss of sensitivity (thermal hypoalgesia). Conservation of good health, the fast appearance of symptoms which correspond well with human responses and the easy induction of nociceptive symptoms are favourable criteria for using this model at 50 microg/kg vincristine dose in the future.

Animals↗

PubMed1999

Dopaminergic and opioidergic mediations of tricyclic antidepressants in the learned helplessness paradigm.

The roles of dopaminergic and opioid neurotransmissions in the activity of three tricyclic antidepressants endowed with different monoamine-reuptake properties [desipramine (DESI), imipramine (IMI), amineptine (AMN)] were examined using a behavioral model of depression in rats; the learned helplessness paradigm. In this model, exposure of rats to inescapable shocks (day 1) produced a subsequent escape deficit in a shuttle box test (days 3, 4, and 5). The escape deficit was reversed by AMN, DESI, and IMI administered twice daily for 5 days (16 and 32 mg/kg/day, p < 0.05, days 3, 4, and 5). In addition, AMN tended to enhance the motor activity of rats during the intertrial intervals, but on the first shuttle-box test only (day 3: p < 0.05, control vs AMN). Haloperidol, a preferential D2 dopamine receptor antagonist, acutely injected IP (37.5 microg/kg), suppressed the behavioral activity of DESI and IMI but not that of AMN. Naloxone, a preferential mu-opioid receptor antagonist, acutely injected IP (0.5 mg/kg), suppressed the behavioral activity of IMI but not that of DESI and AMN. It is concluded that an increased dopaminergic activity is a neurochemical effect common to the different tricyclic antidepressants (via a presynaptic mechanism for AMN and a postsynaptic mechanism for DESI and IMI), whereas an increased mu-opioid neurotransmission does not appear to be essential.

Adrenergic Uptake Inhibitors↗

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↗

PubMed1999

Spinal effect of a neuropeptide FF analogue on hyperalgesia and morphine-induced analgesia in mononeuropathic and diabetic rats.

1DMe, a neuropeptide FF (NPFF) analogue, has been shown to produce antinociception and to enhance morphine analgesia in rats after intrathecal administration. To determine whether 1DMe could correct hyperalgesia and restore morphine efficacy in mononeuropathic (MN) and diabetic (D) rats we examined the spinal effect of 1DMe in MN and D rats without and after spinal blockade of mu- and delta-opioid receptors with CTOP and naltrindole, respectively. The influence of 1DMe on morphine-induced antinociception was assessed in the two models using isobolographic analysis. Whereas 1DMe intrathecally injected (0.1, 1, 7.5 microg rat(-1)) was ineffective in normal (N) rats, it suppressed mechanical hyperalgesia (decrease in paw pressure-induced vocalisation thresholds) in both MN and D rats. This effect was completely cancelled by CTOP (10 microg rat(-1)) and naltrindole (1 microg rat(-1)) suggesting that it requires the simultaneous availability of mu- and delta-opioid receptors. The combinations of morphine: 1DMe (80.6:19.4% and 99.8:0.2%, in MN and D rats, respectively) followed by isobolographic analysis, showed a superadditive interaction, relative to the antinociceptive effect of single doses, in D rats only. In N rats, the combination of morphine: 1DMe (0.5 mg kg(-1), i.v.: 1 microg rat(-1), i.t., ineffective doses) resulted in a weak short-lasting antinociceptive effect. These results show a different efficacy of 1DMe according to the pain model used, suggesting that the pro-opioid effects of the NPFF in neuropathic pain are only weak, which should contribute to hyperalgesia and to the impaired efficacy of morphine.

Analgesia↗

PubMed1999

[Postoperative pain assessment in head and neck cancer surgery: benefit of patient controlled analgesia (PCA)].

Acute postoperative pain has seldom been assessed in head and neck cancer surgery. The estimation of actual pain is more difficult when communication is impaired by tracheotomy or tracheostomia. The aim of the present prospective study was the assessment of analgesia level during the first 48 postoperative hours after head and neck cancer surgery. The analgesic procedure involved intra-venous morphine injected by means of a PCA pump (Patient controlled analgesia). Thirty patients were thus treated after cancer surgery of the larynx or the oropharynx. The protocol included during 48 hours the assessment of pain, using a visual analogic scale (VAS) every fourth hour, while recording the total injected dose of morphine, the localisation of pains, as well as the occurrence of side-effects. The control of postoperative pain was shown to be satisfactory, with a VAS grade smaller than 3 at time zero and kept below this value during 48 hours. At the end of this period, the mean total dose of morphine injected was 38 mg. No case of respiratory depression was even seen. It can be concluded that PCA seems to be an efficient procedure for controlling postoperative pain in head and neck cancer surgery. This technique proved to be better than delivering analgesia on requirement.

Acute Disease↗

PubMed1998

Effect of tachykinin receptor antagonists in experimental neuropathic pain.

The intrathecal effect of 0.1 to 10 microg of RP-67,580 (3aR,7aR)-7,7-diphenyl-2[1-imino-2(2-methoxyphenyl)-ethyl]++ +perhydroisoindol-4-one hydrochloride, CP-96,345 (2S,3S)-cis-(2(diphenylmethyl)-N-[(2-methoxyphenyl) methyl]-1-azabicyclo[2.2.2]octan-3-amine), SR-140,333 (S)-(1-¿2-[3-(3,4-dichlorophenyl)- 1-(3-isopropoxyphenylacetyl)piperidin-3-yl]ethyl¿-4-phenyl-1 -azonia-bicyclo[2.2.2.]-octane,chloride), all neurokinin (NK)1-receptor antagonists, SR-48,968 (S)-N-methyl-N[4-(4-acetylamino-4-[phenylpiperidino)-2-(3,4-dichlorophen yl)-butyl]benzamide, a tachykinin NK2 receptor antagonist and SR-142,801 (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl) piperidin-3-yl)propyl)-4-phenylpiperidin-4-yl)-N-methyl acetamide, a tachykinin NK3 receptor antagonist, and of their respective inactive enantiomers on thresholds of vocalization due to a mechanical stimulus in mononeuropathic (sciatic nerve ligature) and diabetic rats, was examined. The tachykinin NK1 and the NK2 receptor antagonists were antinociceptive in both models, with a higher effect of the former in diabetic rats. The tachykinin NK3 receptor antagonist was weakly effective in diabetic rats only. This indicates a differential involvement of the tachykinins according to the model of neuropathic pain, suggesting a potential role for tachykinin receptor antagonists in the treatment of neuropathic pain.

Analgesics↗

PubMed1998

Assessment of postoperative pain after laryngeal surgery for cancer.

OBJECTIVES: To assess the intensity of postoperative pain after laryngeal surgery for cancer and the efficacy of analgesic injections at fixed hours. DESIGN: A prospective clinical study performed during the 3 days following laryngeal cancer surgery. SETTING: A university medical center. PATIENTS: Fifteen men (age range, 38-74 years) having just undergone a partial or total laryngectomy for epidermoid carcinoma. INTERVENTIONS: The analgesic treatment consisted of intravenous administrations at fixed hours (propacetamol or nalbuphine hydrochloride), with the possibility of rescue doses on demand. Pain and anxiety were assessed by means of visual analog scales (graduated from 0-10) every 3 hours on postoperative day 1, then every 6 hours on postoperative days 2 and 3. Objective criteria, ie, heart and respiratory rates and mean blood pressure, were measured with the same schedule. MAIN OUTCOME MEASURES: Postoperative pain and anxiety intensities and their variations were analyzed. Correlations between postoperative pain and other criteria were researched. RESULTS: Postoperative pain had a high initial level (maximum median, 7), then decreased and reached a score of 3 at the 30th hour. Unpredictable individual peaks of pain were reported. Anxiety was never high (maximum median, 4). No individual correlation was found between pain and objective parameters. CONCLUSIONS: After laryngeal surgery for cancer, pain can reach high levels, particularly in the first hours following recovery. Analgesic administrations at fixed hours are not effective enough. Postoperative analgesic treatment should aim to prevent the high initial pain and be individually adapted.

Acetaminophen↗

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↗

PubMed1998

Reversal of learned helplessness by morphine in rats: involvement of a dopamine mediation.

The aim of this study was to examine the role of dopamine neurotransmission in the effects of morphine in the learned helplessness paradigm in rats, a generally recognized model of depression. In this model, rats first exposed to inescapable shocks (stressed rats) exhibited an escape deficit in a subsequent shuttle-box test performed 48 h later for 3 consecutive days. The numbers of escape failures and intertrial crossings (motor activity during each intertrial interval) were recorded. Morphine was injected twice daily for 5 days (6 mg/kg/day, s.c.), and haloperidol, a preferential D2-dopamine receptor antagonist, was injected i.p. 15 min before each shuttle-box session. At the highest dose tested (150 microg/kg) haloperidol mimicked the behavioral deficit produced by inescapable shocks. A 37.5 microg/kg dose of haloperidol, which was ineffective by itself, reversed the morphine-induced improvement of escape behavior in previously stressed rats and the morphine-induced increase in intertrial activity in both stressed and nonstressed animals. These results support roles (a) for a dysregulation of dopaminergic neuronal activity in the expression of escape deficit subsequent to an inescapable aversive situation, and (b) for a dopaminergic mediation in the effects of morphine in the learned helplessness paradigm.

Animals↗

PubMed1998

Evidence for a role for bulbospinal pathways in the spinal antinociceptive effect of systemically administered vapreotide in normal rats.

Numerous neurotransmitters are involved in nociceptive transmission or regulation. Several reports have shown the analgesic effects of somatostatin and its analogues. Somatostatin, when given intrathecally, markedly reduced pain in cancer patients. Somatostatin analogues that possess a longer half-life time are more convenient for therapeutic use. Vapreotide, a somatostatin analogue, was shown to induce a long-lasting antinociceptive effect in rats. We studied the site and the mechanism of action of vapreotide in rats using the paw pressure test. Intrathecal administration of vapreotide induced no antinociception. Systemically administered vapreotide-induced antinociception was inhibited by several intrathecal (i.t.) administered antagonists (yohimbine, naloxone and to a lesser degree tropisetron). These results show a lack of spinal effect and suggest a supraspinal site of action with an involvement of noradrenergic and to a lesser degree serotonergic bulbospinal pathways. In addition, spinal opioid receptors also seen to be involved.

Adrenergic alpha-Antagonists↗

PubMed1998

Is the reduced efficacy of morphine in diabetic rats caused by alterations of opiate receptors or of morphine pharmacokinetics?

Because it generally is admitted that neuropathic pain is resistant to opioid analgesia, we investigated the effect of morphine on hyperalgesia in streptozocin-induced diabetes in rats. The antinociceptive effect of morphine (0.5-4 mg/kg i.v.) on mechanical (paw pressure test), thermal (tail immersion test) and chemical (formalin test) hyperalgesia was reduced. To clarify the mechanisms involved in the alteration of morphine analgesia, the binding characteristics of mu and delta receptor agonists and the pharmacokinetics of morphine and its glucuronide metabolites morphine 3-glucuronide and morphine 6-glucuronide were determined. KD and Bmax values for [3H][D-Ala2,(Me)Phe4, Gly(ol)5]enkephalin and [3H][D-Pen2,D-Pen5]enkephalin to cerebral mu and delta opiate receptors were not altered by diabetes. Likewise, the plasma maximal concentration of morphine and metabolites, as well as the area under the curve, did not differ between diabetic and normal rats. Only the total clearance and the apparent volume of distribution of morphine were increased in diabetic rats, which suggests that the diabetes-induced glycosylation of proteins might increase the distribution of morphine in the aqueous compartment. These data indicate that the reduced analgesic effect of morphine caused by diabetes cannot be explained by a decrease in opiate-receptor affinity or density but rather by kinetic alteration of morphine (increase of total clearance and of volume of distribution in comparison with healthy animals).

Analgesia↗

PubMed1997

Effects of clomipramine and desipramine on a C-fiber reflex in rats.

A C-fiber nociceptive reflex evoked by electrical stimulation within the territory of the sural nerve, was recorded from the ipsilateral biceps femoris muscle in urethane anesthetized rats. Intravenously administered clomipramine and desipramine produced a dose-dependent depression of the C-fiber reflex. High doses of intrathecal desipramine also inhibited the C-fiber reflex, while similar intrathecal doses of clomipramine produced only a modest inhibition of the response. Intracerebroventricular administration of clomipramine decreased dose-dependently the C-fiber reflex whereas intracerebroventricular desipramine increased this reflex. These findings suggest that tricyclic antidepressants with noradrenergic selectivity, as desipramine, inhibit the spinal processing of C inputs by acting directly at the spinal cord level, while those with serotonergic spectra, as clomipramine, depress the C-fiber-evoked spinal reflex by acting at a supraspinal modulatory site.

Animals↗

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

Magnesium deficiency induces an hyperalgesia reversed by the NMDA receptor antagonist MK801.

The aim of this study was to determine the changes of the nociceptive thresholds in response to an acute mechanical stimulus (paw pressure) in magnesium (Mg)-deficient rats, and the involvement of the NMDA receptor in these changes. Changes in vocalization thresholds was determined after 7 days of feeding with a Mg-depleted diet. Compared with the control group, Mg-deficient rats showed a significant decrease in the vocalization thresholds (-35.8 +/- 2.5%, p < 0.001) reflecting hyperalgesia. In Mg-deprived rats, three doses (0.06, 0.12 and 0.24 mg/kg s.c.) of dizocilpine (MK801), a non-competitive NMDA receptor antagonist, significantly reversed the hyperalgesia in a dose-dependent manner for at least 48 h. No effect of MK801 was observed in the control group. These data provide evidence that Mg deficiency could constitute a new model of hyperalgesia involving NMDA receptors.

Analysis of Variance↗

PubMed1997

Effect of tolcapone on plasma and striatal apomorphine disposition in rats.

The influence of tolcapone, an inhibitor of catechol-O-methyl transferase, was evaluated on the disposition of apomorphine, a dopamine agonist used to treat Parkinson's disease, to explain a previously observed increase of duration of the effect of apomorphine associated with tolcapone. Sampling was performed in rats before and at different times after administration of apomorphine and following that of tolcapone or saline. Both in plasma and striatum, times to reach maximal-concentration and maximal concentrations did not significantly differ between the two groups but the elimination half-life times and areas under the curve were significantly greater following tolcapone treatment than in the saline group. These results show that tolcapone can increase plasma apomorphine bioavailability by modifying its liver catabolism.

Animals↗

PubMed1997

Effect of intrathecal serotonin on nociception in rats: influence of the pain test used.

The involvement of serotonin (5-HT) in the modulation of nociceptive impulse in the spinal cord has been widely studied. However, its activity, considering the nature of noxious stimuli and the type of 5-HT receptors involved, merits to be further elucidated. The present behavioural study was performed to compare the dose-antinociceptive effect relationship of 5-HT in rats, after intrathecal (i.t.) injection (10 microliters/rat), using mechanical (paw pressure), thermal (tail immersion and tail-flick) and chemical (formalin) pain tests. In rats submitted to the paw pressure test, 5-HT was found to possess a dose-dependent antinociceptive activity (0.01, 0.1, 1, 10 and 20 micrograms/rat) when vocalization threshold was assessed as a pain parameter. A peak effect occurred 5 min after the injection and the effect was maintained for 45 min. The lowest active dose was 0.1 microgram (maximum increase in vocalization thresholds, 23 +/- 3%) and a plateau was observed for 10 micrograms and 20 micrograms (maximum increase in vocalization thresholds, 72 +/- 7% and 71 +/- 6%, respectively). When paw withdrawal was assessed, 5-HT induced a weak hyperalgesic effect for the highest dose (60 micrograms), while other doses were ineffective. In the tail-immersion (warmth and cold) and tail-flick tests, different doses (0.01, 0.1, 1, 10, 30, 60 and 100 micrograms/rat) were studied. In the two immersion tests, only the highest doses (60 micrograms and 100 micrograms) significantly increased the withdrawal thresholds from 5 to 45 min after the injection. The maximum effect was observed at 5 min (23 +/- 4% and 21 +/- 6% for 60 micrograms; 27 +/- 3% and 30 +/- 6% for 100 micrograms in the warmth and cold immersion test, respectively). In the tail-flick test, the doses of 30, 60 and 100 micrograms/rat dose-dependently and significantly increased the withdrawal thresholds from 5 to 45 min after the injection, with a maximum effect at 5 min (30 +/- 5% for 30 micrograms; 37 +/- 6% for 60 micrograms; and 45 +/- 4% for 100 micrograms). In the formalin test, 5-HT (10, 25, 50, 75 and 100 micrograms/rat) produced dose-related antinociception. The nociceptive response (licking of the injected paw) was significantly reduced from 25 micrograms (-59 +/- 11%) in the early phase, whereas the lowest active dose in the late phase was 50 micrograms (-46 +/- 17%). For both phases, a total inhibition was obtained with 100 micrograms. It is concluded that the effect of 5-HT on pain tests may differ according to the applied stimulus and the parameter assessed; unspecific effects of 5-HT may modify motor reactions to noxious stimuli. Mechanical test (assessment of vocalization) was the most sensitive to 5-HT. These observations are of importance in order to further study the pharmacological mechanisms involved in 5-HT spinally 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↗