Biomedical subjects

Alain Eschalier

Publications and source records attributed to Alain Eschalier.

48 records · Page 3Linked to original sources

PubMed2002

Absence of painful neuropathy after chronic oral fluoride intake in Sprague-Dawley and Lou/C rats.

The possibility that chronicle oral ingestion of fluoride-rich water could modify peripheral pain sensitivity was studied in two strains of adult rats, Sprague-Dawley and Lou/C rats. Sodium fluoride was given orally in water to male Sprague-Dawley (75 and 150 ppm) and Lou rats (150 ppm) for 15 and 27 weeks, respectively. Using classical behavioural evaluation methods of pain symptoms, only slight tendencies to a thermal hyperalgia and a mechanical allodynia were observed in Sprague-Dawley rats.

Administration, Oral↗

PubMed2002

Paracetamol exerts a spinal, tropisetron-reversible, antinociceptive effect in an inflammatory pain model in rats.

Experiments were performed in carrageenin-treated rats to study, the antinociceptive and anti-inflammatory effects of paracetamol intravenously (i.v.) or intrathecally (i.t.) injected on rats submitted to a mechanical noxious stimulus. The influence of intrathecal tropisetron, a 5 hydroxytryptamine(3) (5-HT(3)) receptor antagonist, on the antinociceptive effects of paracetamol, was also studied. Paracetamol induced a significant antinociceptive effect after (100, 200 and 300 mg/kg) i.v. and (50, 100 and 200 microg/rat) i.t. injection, but no change occurred on edema volume. The effect of paracetamol was totally inhibited by tropisetron (10 microg/rat, i.t.). The foregoing results demonstrate that, in conditions of inflammatory pain, paracetamol exerts a central antinociceptive effect involving spinal 5-HT(3) receptors, without inducing any anti-inflammatory action. These data, give further arguments to consider paracetamol as a central analgesic drug which must be distinguished from non-steroidal anti-inflammatory drugs (NSAIDs), which justifies the usual combination of paracetamol in post-operative pain.

Acetaminophen↗

PubMed2002

Assessment of the relationship between hyperalgesia and peripheral inflammation in magnesium-deficient rats.

Magnesium-deficient rats develop simultaneously a significant lowering of nociceptive threshold and a generalized inflammation. We investigated the relationship between these two phenomena by testing drugs that are able to suppress the inflammation in this model. In weaning rats fed a magnesium-depleted diet for ten days, the nociceptive threshold was assessed by the paw pressure test and the inflammation by a clinical score. A non-steroidal anti-inflammatory drug (piroxicam); antagonists of H1 and H2 receptors (astemizole and cimetidine. respectively); a glucocorticoid (dexamethasone); an inhibitor of mastocyte degranulation (cromoglycate); and estradiol benzoate were used to block the inflammatory response. Dexamethasone and estradiol significantly suppressed the inflammation (p < 0.001 vs control group). Cromoglycate showed a delayed anti-inflammatory effect (p < 0.01 vs control group on D10). The combination of astemizole and cimetidine partially blocked the inflammation process, whereas astemizole and piroxicam were without effect. Regardless of the effect of the test drugs on inflammation, no change in the time course of hyperalgesia was observed. These data support the view that hyperalgesia induced by the magnesium-depleted diet is not a consequence of the inflammatory process.

Animals↗

PubMed2002

Impact of ageing on the antinociceptive effect of reference analgesics in the Lou/c rat.

1. Research on the evolution of experimental pain perception and on the achievement of analgesia with ageing has led so far to contradictory results. 2. This study investigated in the rat the impact of ageing on the antinociceptive effect of reference analgesics, acetaminophen (50, 100, 200, 400 mg kg(-1) po), aspirin (50, 100, 200, 400 mg kg(-1) sc), clomipramine (5, 10, 20, 40 mg kg(-1) sc) and morphine (1.25, 2.5, 5, 10 mg kg(-1) sc). 3. Lou/c rats were chosen because they provide a model of healthy ageing and they do not develop obesity with age. Three groups of 40 rats each (mature (4 months), middle-aged (18 months) and old (26 months)), were treated with each drug at 14 days interval. Two tests were used: a thermal test (tail immersion in 48 degrees C water and measurement of reaction latency) and a mechanical test (paw pressure and measurement of struggle threshold). 4. Results confirm the increased mechanical sensitivity to pain and no change in thermal sensitivity for old rats compared to mature and middle-aged animals. They show a marked decrease in the effect of morphine with age and no age-related effect for acetaminophen, aspirin or clomipramine. Plasma levels of morphine and metabolites are not different in the three age groups. 5. It is likely that the influence of age on morphine analgesia is linked mainly to pharmacodynamic rather than pharmacokinetic changes.

Acetaminophen↗

PubMed2002

Involvement of N-methyl-D-aspartate receptors in nociception in the cyclophosphamide-induced vesical pain model in the conscious rat.

We previously showed that the intraperitoneal (i.p.) administration of 200mg/kg cyclophosphamide, an antitumoral agent, modified the behaviour of rats with cystitis induced by acrolein, a toxic urinary by-product of cyclophosphamide. This behaviour, (namely decreased breathing rate, closing of the eyes, and specific postures), was scored to indirectly assess the nociception elicited by the cystitis and to use this experimental model as a vesical pain model. Here we investigated the involvement of the N-methyl-D-aspartate (NMDA) receptors and thus of the excitatory amino acid system in this model. We administered dizocilpine (0.01 to 0.1mg/kg intravenously (i.v.) and 1 to 20 microg/rat intrathecally (i.t.)) and ketamine (5 and 10mg/kg i.v. and 50 to 1000 microg/rat i.t.), two non-competitive NMDA receptor antagonists that bind to the channel site, and AP-5 (0.01 to 1mg/kg i.v. and 20 to 500 microg/rat i.t), a competitive antagonist that binds to the glutamate site. Whichever the route of administration (i.v. or i.t.), dizocilpine dose-relatedly reduced the behavioural disorders induced by cyclophosphamide. Systemic ketamine also dose-dependently, though transiently, reduced the effects of cyclophosphamide, but ketamine i.t. and AP-5 i.v. and i.t. did not induce any reduction of these effects.These results (i) demonstrate that in the cyclophosphamide-induced vesical pain model NMDA receptors are involved in the nociception, as shown by the effects of dizocilpine and systemic ketamine, (ii) reveal marked differences in the data obtained with various NMDA receptor antagonists, possibly due to their physicochemical properties, to the animal pain model used, to the noxious stimulus applied or to any combination of these factors.

Acrolein↗

PubMed2002

Magnesium increases morphine analgesic effect in different experimental models of pain.

BACKGROUND: An excess of excitatory pathway activation via N-methyl-D-aspartate (NMDA) receptors has been described in neuropathic pain that responds poorly to morphine. However, in this situation, several published data sets show that coadministration of NMDA receptor antagonists restores the efficacy of opioids. Considering that magnesium behaves like an NMDA receptor antagonist, we investigated the effect of the combination of magnesium and morphine in experimental models of chronic and tonic pain. METHODS: Mechanical hyperalgesia was assessed with the paw-pressure test in mononeuropathic (chronic constrictive injury model) and diabetic rats. Behavioral reactions were scored in a model of inflammation induced by formalin. The animals were assigned to one of three groups according to the intraperitoneal pretreatment: magnesium (30 mg/kg x 3), magnesium (30 mg/kg), and saline. Before testing, morphine was injected intravenously in mononeuropathic (0.3 mg/kg) and diabetic rats (1 mg/kg) and by the subcutaneous route in rats with the formalin test (1.5 mg/kg). RESULTS: Magnesium alone induced a significant antihyperalgesic effect in mononeuropathic and diabetic rats after a cumulative dose of 90 mg/kg. Furthermore, it significantly increased morphine analgesia, regardless of the loading dose used (30 or 90 mg/kg) in the two models of neuropathic pain. In the formalin test, magnesium alone did not have a significant effect. However, in combination with morphine, it revealed the analgesic effect of this opiate. CONCLUSIONS: These data show that magnesium amplifies the analgesic effect of low-dose morphine in conditions of sustained pain. Considering the good tolerability of magnesium, these findings may have clinical applications in neuropathic and persistent pain.

Analgesics, Opioid↗

PubMed2002

[Standards, options and recommendations for the use of medical analgesics for the treatment of pain arising from excess nociception in adults with cancer (update 2002)].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of french cancer centers (FNCLCC), the 20 French cancer centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for the use of medical analgesics for the treatment of pain arising from excess nociception in adults with cancer according to the definitions of the Standards, Options and Recommendations project. METHODS: In 1996, a working group, set up by the FNCLCC published clinical practice guidelines for pain management in adult and paediatric patients with cancer. In the light of the evolution of our knowledge, and practice these guidelines need to be updated. The section on "medical analgesic treatments" in the document published in 1996 was examined by the working group to identify which questions should be updated. These questions and the relevant key words were used to develop a search strategy which was used to search Medline , and for particular questions, Embase , from January 1994 to March 1999, for relevant references, published in English or French. RESULTS: For this update, only a few randomised clinical trials were identified, and their conclusions were generally weak. Thus much of the information in this document is based on the World Health Organisation (WHO) guidelines and represents the "state of the art" on this subject in France and is supported by expert agreement. Some changes to the original SOR are presented, eg. methods of titration, prescription of new opioids, opioid rotation. We also present a synthesis of recent pharmacological and regulatory data. The integral version is available on the FNCLCC web site (http://www.fnclcc.fr/sor.htm).

Adult↗

PubMed2000

Spinal effect of the cholecystokinin-B receptor antagonist CI-988 on hyperalgesia, allodynia and morphine-induced analgesia in diabetic and mononeuropathic rats.

Since evidence points to the involvement of cholecystokinin (CCK) in nociception, we examined the effect of intrathecal CI-988, an antagonist of the CCK-B receptors, on mechanical hyperalgesia and allodynia in normal, mononeuropathic and diabetic rats,. Owing to the anti-opioid activity of CCK, it has been suggested that hyperactivity in the spinal CCK system is responsible for the low sensitivity of neuropathic pain to opioids. We therefore also evaluated the effect of the combination of i.t. CI-988 + i.v. morphine on mechanical hyperalgesia in diabetic and mononeuropathic rats using isobolographic analysis. Although ineffective in normal rats, CI-988 induced antinociceptive effects in diabetic (290 +/- 20 g with a cut-off of 750 g) and mononeuropathic (117 +/- 16 g; cut-off 750 g) rats, suggesting an involvement of the CCKergic system in neurogenic pain conditions. The combination of CI-988 and morphine showed a superadditive interaction in the diabetic rats only (477 +/- 16 g; cut-off 750 g), in comparison with the antinociceptive effect of each drug. In addition, CI-988 exhibited a weak anti-allodynic effect in mononeuropathic rats, and no anti-allodynic effect in diabetic rats. These results show the CCK-B receptor blockade-mediated antinociceptive effects and reveals the antinociceptive action of morphine in diabetic rats after CCKergic system inhibition.

Analgesia↗

PubMedDate not supplied

Serotonin and experimental pain in healthy young volunteers.

OBJECTIVE: The role of serotonin in the modulation of nociceptive input has been widely studied, and a link between serum serotonin (S-5HT) and pain thresholds elicited in patients with chronic painful pathologies has been shown. In the light of contradictory concepts on pain message modulation by S-5HT, this study tries to define whether S-5HT displays a nociceptive or antinociceptive role in experimental pain evaluation in healthy volunteers. DESIGN: In 20 healthy young volunteers, 10 men and 10 women (21 +/- 2 years old), blood serotonin measurements were made, pressure pain thresholds was determined, and statistical analysis was performed. RESULTS: This study showed a significant negative correlation of total blood serotonin with experimental pain detection threshold (P < 0.05, r = 0.444), but not with pain tolerance, while sex-related correlations of serotonin and thresholds were not significant. Lower serotonin concentration (P = 0.02), higher pain threshold (P < 0.01), and higher pain tolerance (P = 0.02) in men than in women were observed. CONCLUSION: Low pain detection thresholds may be explained by a peripheral nociceptive effect of serotonin. Pain tolerance does not, however, encompass a similar pattern of serotoninergic involvement in pain control and may include other components that remain to be elucidated. These results call for further studies on a larger population.

Adult↗

PubMedDate not supplied

Impact of age, gender and cognitive functioning on pain perception.

BACKGROUND: Experimental data on nociception in the elderly have so far been contradictory and most of these have been obtained using psychophysical methods with little attention paid simultaneously to the state of cognition and the psychometric performance of the subjects. OBJECTIVE: The aim of this study was twofold: (1) to evaluate the impact of age on experimental nociception thresholds, and (2) to investigate the interactions of age, sex, cognition and psychometric performance with nociception thresholds. METHODOLOGY: (1) Two groups, one young and one elderly, of 42 healthy participants each, 21 males and 21 females, were compared as regards nociception thresholds with thermal and mechanical stimuli (heat and pressure detection and tolerance thresholds). (2) The elderly group took cognitive (mini-mental test), psychometric (choice reaction time) and psychophysical tests in auditory (sensibility, tolerance, discrimination) and nociceptive fields. RESULTS: This study shows that (1) pressure nociception decreases with age especially in males, while thermal thresholds are not modified, and (2) correlations exist between cognitive function, psychometric performance, tolerance to loud sounds and tolerance to mechanical noxious stimuli. CONCLUSION: Our results suggest that cognitive and psychomotor parameters have to be taken into account when assessing experimental nociception in the elderly. Further studies are needed to evaluate possible report biases and to assess these interactions in old patients with pain and in mildly sensory, cognitive or motor impaired elderly subjects.

Adult↗

PubMedDate not supplied

Memory impairment means less pain for mice.

BACKGROUND: Clinical observations have reported that individuals with memory deterioration, like in Alzheimer's disease, display a lesser pain sensibility than patients with no cognitive impairment. OBJECTIVE: To clarify the link between pain and loss of memory, we studied how memory-impaired mice behave when submitted to hotplate nociceptive tests. METHODS: For 5 days (D1-D5), male CD1 mice were injected daily intraperitonealy with saline or scopolamine (s, an anticholinergic drug, 0.2 mg/kg) or ketamine (k, an N-methyl-D-aspartate receptor antagonist (NMDAr), 2.5 mg/kg), at doses leading to memory impairment with no analgesic effect. From D6 to D9, all received saline only. They were placed on the hotplate and removed at the first sign of discomfort, response time being recorded. RESULTS: From D1 to D5, reaction time decreased significantly in controls only and did not change in mice with scopolamine or ketamine. From D6 to D9, response times decreased (p < 0.05 (s) and p < 0.0001 (k)) to reach the steady state of control animals. At D5, response time was significantly prolonged for scopolamine (p < 0.01) and ketamine (p < 0.05), compared to controls. CONCLUSION: These results show that pain sensibility needs the integrity of the central cholinergic and of the NMDA systems, and that mice with memory impairment display a lesser pain sensibility than normal mice. Further research on the complex interactions of receptors and neurotransmitters involved in pain and cognition could assist in gaining a better understanding of pain and analgesia in patients with memory impairment and in demented individuals.

Animals↗

PubMedDate not supplied

[Standards, options and recommendations for the use of medical analgesics for the treatment of pain arising from excess nociception in adults with cancer (update 2002): opioid analgesics with the exception of morphine by mouth and the rotation].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the federation of French Cancer Centers (FNCLCC), the 20 French cancer centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for the use of opioid analgesics with the exception of oral morphine and for opioid rotation related to the treatment of nociceptive pain in adults with cancer according to the definitions of the Standards, Options and Recommendations project. METHODS: In 1996, a working group, set up by the FNCLCC published clinical practice guidelines for pain management in adult and paediatric patients with cancer: In the light of the evolution of knowledge, and practice these guidelines need to be updated The section on "médical analgesic treatments" in the document published in 1996 was examined by the working group to identify which questions should be updated. These questions and the relevant key words were used to develop a search strategy which was used to search Medline, and for particular questions, Embase, from January 1994 to March 1999, for relevant references, published in English or French. RESULTS: For this update, only a few randomised clinical trials were identified, and their conclusions were generally weak. Thus much of the information in this document is based on the World Health Organisation (WHO) guidelines and represents the "state of the art" on this subject in France and is supported by expert agreement. Some changes to the original SOR are presented, particularly for the prescription of new opioids and opioid rotation. The full text of this SOR is available on the FNCLCC web site (http ://www.fnclcc.fr).

Analgesics, Opioid↗