Adoption and validation of the international normalized ratio for monitoring oral anticoagulant therapy: The situation in 1989

The INR/ISI system has been validated in multicenter trials. The system provides a reliable scale for the intensity of oral anticoagulation. It has been recognized that the ISI is slightly dependent on the instrument used for prothrombin time determination. External quality assessment (EQA) of the INR in national programs should be stimulated. EQA results suggest that the precision of the INR can be improved. Many physicians prescribing coumarin congeners are not familiar with the INR system. Improvement of the situation can only be achieved by continuous education. Presented at the ‘2nd International Symposium on Standardization and Quality Control of Coagulation Tests: Implications for the Clinical Laboratory’, Rome, September 28–29, 1989.     

Laboratory and therapeutic control in the Thrombosis Centre Rotterdam using chromogenic prothrombin time tests

Growing interest is observed in chromogenic substrate assays, because of their better precision, performance and possibilities for automation. Applied to a Cobas Bio centrifugal analyzer, we compared Nycotest-Chrom (N-test) and Thromboquant-PT (Tbq) with Thrombotest (TT). Precision tests were performed with samples from 4 plasma pools: normal (45 sec), low (100 sec), middle (150 sec) and high (200 sec) segments of the therapeutic range of TT. N-test had the best precision profile in both intraassay and interassay determinations compared with Tbq. Both chromogenic substrate assays were better than TT in this respect. By orthogonal regression a provisional therapeutic range was calculated from 312 determinations and later adjusted in a confirmation experiment with natural logarithm regression in 946 determinations. Compared with a TT range of 105–180 sec, the therapeutic ranges were 71–120 sec for N-test and 63–103 sec for Tbq. In a clinical therapeutic control phase, 110 patients were randomized in equal proportions to two groups A and B. Every 2 weeks for a period of 16 weeks, blood samples were tested for N-test, Tbq and TT. In group A, dose adjustment was based on N-test, and in group B on Tbq. The monitoring physician was blinded for Tbq and TT in group A and for N-test and TT in group B. No differences were found between the groups for mean TT, N-test, Tbq or mean dosage, nor differences were found in complication rates. A definite therapeutic range was compiled using sensitivity/specificity curves together with their 95% confidence limits. Given TT 105–180 sec, the therapeutic range of N-test is from 80 (95% confidence limits: 77–82) to 110 (95% confidence limits: 108–115) sec, and of Tbq from 68 (95% confidence limits: 66–71) to 95 (95% confidence limits: 91–98) sec. It was concluded that the two chromogenic substrate assays performed equally safe in the monitoring of patients on oral anticoagulant therapy, despite differences in diagnostic correspondence with the reference TT. Presented at the ‘2nd International Symposium on Standardization and Quality Control of Coagulation Tests: Implications for the Clinical Laboratory’, Rome, September 28–29, 1989.     

凝血酶原时间ISI/INR系统测定中的一些问题及改进意见

目的对凝血酶原时间(PT)测定ISI/INR系统出现的一些问题提出相应的改进建议。方法对上海市12家医院在用的仪器和匹配的PT试剂,对日常使用的正常血浆平均凝血酶原时间(MNPT)作调研实测,将结果进行分析;调查试剂的仪器特定(spec ific)国际敏感度指数(ISI)值与世界卫生组织(WHO)的手工法ISI定标值之间的差异;用2种已知国际标准化比值(INR)的异常参比血浆代替WHO的ISI系统作质控并行比较。结果12家中有4家日常使用的平均正常凝血酶原时间(MNPT)明显偏离实测值,分别为0.8、0.9、1.0和1.8 s。用WHO CRM149R参比,用手工法标定的凝血活酶和109 mmol枸橼酸钠抗凝的不同PT值血标本,在Sysm ex1500型、C.2000型仪器上测定试剂的仪器特定ISI,其结果比手工法分别减少4.1%和4.7%,但采用HEPES-枸橼酸钠抗凝剂标本时,2种型号仪器的特定ISI比手工法分别减少16.7%及7.7%。用已知INR异常参比血浆,国产品与进口品对照的结果良好。结论受调研12家中,有4家血凝分析仪器调研时实测的MNPT明显偏离日常使用值。有几家医院试剂的仪器特定ISI值也存在问题,建议纠正。用已知INR异常参比血浆代替WHO手工法标定凝血活酶ISI法作质控,使用简便,又不需MNPT参数,值得推广。     

The ruptured Achilles tendon: operative and non-operative treatment options

The Achilles tendon is the strongest and thickest tendon in the human body. Like any other tendon in the body, however, it is susceptible to rupture. Many surgeons advocate early operative repair of the ruptured Achilles tendon, citing decreased re-rupture rates and improved functional outcome. Waiting for surgical repair for longer than one month may lead to inferior functional results postoperatively. Non-operative treatment has higher re-rupture rates as compared to surgically repaired tendons, but may be the treatment of choice in some patients. While for many years, patients were rigidly immobilized in a non-weightbearing cast for 6–8 weeks postoperatively, newer studies have shown excellent results with early weightbearing, and this is quickly becoming the standard of care amongst many physicians.     

Effects of serum storage on the determination of cholesterol

Cholesterol determined by 4 different enzymatic commercial kits and by the dry chemistry Reflotron system was higher in serum stored at 4 °C and at −20 °C than in fresh serum. The effects of storage seem to be temperature-dependent. In fact, cholesterol values significantly increased only after 2h of freezing. The prolongation of freezing up to 2 weeks was not followed by further significant changes. In serum stored at 4 °C the increase in cholesterol was slower than in frozen serum. Both free and esterified cholesterol underwent an increase after storage. When cholesterol was determined by a chemical method (sulfuric acid-ferric chloride) after extraction with ethyl acetate and ethanol, no difference was observed in fresh and stored serum. Cholesterol, triglycerides and apoproteins A-I and B underwent parallel changes after storage both in whole serum and fractionated lipoproteins. Our findings strongly suggest that in serum stored at positive or negative temperature there is an alteration of the lipoprotein molecules which allows an easier availability of cholesterol for the enzyme-substrate reaction than in fresh serum. Current enzymatic methods underestimate (about 10%) cholesterol when the analysis is performed on fresh serum.     

A simple aspiration test to determine the accuracy of oesophageal placement of fine-bore feeding tubes

Objective  To evaluate whether a simple aspiration test can be used to accurately confirm the correct placement of fine-bore feeding tubes in the oesophagus and prevent their inadvertent placement in the bronchial tree. Design  We conducted an ethically approved, randomised, blinded trial to assess the accuracy of a simple aspiration test to differentiate between oesophageal and tracheal placement. Setting  A tertiary referral cardiothoracic surgical unit. Patients and participants  Twenty patients under-going elective cardiac surgery. Intervention  Once anesthetised, a fine-bore feeding tube was inserted into the oesophagus or trachea and a researcher, blinded to the position, then performed the test. This involved attempted aspiration of ≥10 ml of air before and after insufflation of 10 ml of air and comparison with capnography, a test that has been shown to be highly sensitive and specific. Measurements and results  With this small number of patients, the test accurately differentiated between ten oesophageal and ten tracheal placements. Conclusions  A simple aspiration test could be a useful adjunct to prevent inadvertent bronchial placement of fine-bore feeding tubes. Careful attention must be paid to the technique to ensure that no false positives occur.     

The use of recombinant factor VIII in the management of Hemophilia

Recombinant factor VIII is currently in the late stages of clinical trials. The available studies indicate that the product is safe and well-tolerated, and appears to be free of virus diseases such as HIV and hepatitis infections. Based on these early studies, recombinant coagulation factors appear to have enonnous promise and potential for transfusion medicine. The synthesis of large quantities of safe material may lead to the development of techniques for daily administration of factor VIII aimed at the prevention of joint and soft tissue bleedings. There is also the promise of decreased costs, as techniques for the efficient synthesis of recombinant proteins are refined further.     

Influence des agonistes morphiniques sur la motricité intestinale normale et pathologique

Résumé  La morphine et ses dérivés à propriétés agonistes des récepteurs μ, possèdent des effets sur la motricité gastrointestinale et colique. Aux doses actives sur la douleur, la morphine inhibe l’évacuation gastrique et ralentit le transit intestinal et colique. Ces effets sont principalement d’origine centrale pour l’évacuation gastrique, essentiellement périphériques au niveau de l’intestin grêle et d’origine mixte pour le c?lon. Alors que sur le plan moteur on assiste à une inhibition motrice, par contre les effets anti-transit de la morphine au niveau de l’intestin grêle et du c?lon relèvent d’une action de stimulation permanente à tous les niveaux sous forme de séries de contractions simultanées et stationnaires qui empêchent la progression du contenu. Enfin, en période d’iléus postchirurgical, l’utilisation de morphine peut entra?ner des effets moteurs puisque ceux-ci apparaissent pour des doses de morphine n’ayant pas encore d’effets antalgiques et freiner la reprise du transit.

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Summary  Morphine and its derivatives with μ agonist affinities, affect gastrointestinal and colonic motility. At active doses on pain, morphine inhibits gastric emptying and slows down intestinal and colonic transit. These effects are of central origin for gastric emptying, peripheral for intestinal motility and both central and peripheral for the colon. While morphine inhibits gastric contractions, in contrast, morphine stimulates intestinal and colonic motility with stationnary contractions responsible of its inhibitory effects on intestinal and colonic propulsion of digesta When administered during post-surgical ileus, morphine may delay the occurrence of gas and the recovery of gastrointestinal transit: these effects been observed for doses similar or equal to those able to relief pain sensation.

Texte présenté lors du Congrès SFD-SOFRED des 15–17 juin 2000.     

Evaluation critique des modèles expérimentaux de «douleur chronique» chez l’animal

Résumé  De très nombreux modèles de ?douleurs chroniques? ont été développés au cours de ces dernières années. Ces travaux ont surtout concerné les douleurs neuropathiques et, de fa?on schématique, les modèles disponibles aujourd’hui peuvent être regroupés en deux grandes catégories. Les premiers, et les plus anciens, peuvent être considérés comme des modèles étiopathogéniques dans la mesure où ils reproduisent une lésion nerveuse (traumatique le plus souvent) ou un mécanisme lésionnel (métabolique ou toxique) que l’on peut rencontrer en clinique. Bien qu’ils aient contribué à fournir de nouvelles hypothèses physiopathologiques, la pertinence et la signification clinique de ces modèles, notamment les modèles de section nerveuse complète qui ont été les plus utilisés, a fait l’objet de nombreuses discussions et controverses. En effet, les modifications comportementales qu’ils induisent (comportement d’automutilation) paraissent très éloignés des observations cliniques. Ceci a conduit au développement de nouveaux modèles qui correspondent davantage à des modèles ?symptomatiques? car ils ne visent pas à reproduire une lésion ou une pathologie cliniques, mais une symptomatologie proche de celle observée chez les patients. Ces modèles qui reposent sur la réalisation de lésions nerveuses partielles (constriction lache du nerf sciatique, par exemple) se sont surtout révélés intéressants pour l’étude des douleurs provoquées (phénomènes d’allodynie et d’hyperalgésie). Ils ont été très utilisés dans le cadre d’études pharmacologiques dont les résultats sont cependant très discordants par rapport aux données cliniques disponibles. Ainsi, si ces modèles ont fait la preuve de leur grande sensibilité à l’action des antalgiques, leur spécificité semble en revanche beaucoup plus modeste, ce qui a fait émettre des doutes quant à leur valeur prédictive et, de fa?on plus générale, quant à leur signification clinique. Ces modèles correspondent probablement à un ou plusieurs sous-groupes de patients, mais de nouvelles études expérimentales et cliniques paraissent aujourd’hui nécessaires pour mettre davantage en relation les données fondamentales et cliniques.

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Summary  Numerous animal models of ?chronic pain? have been developed during the last few years. These studies have concerned mainly neuropathic pain. Schematically, these models can be divided into two broad categories. The models in the first category, can be considered as ?etiopathogenic? since the lesion aimed at reproducing, in animals (usually the rat) a lesion (e.g., traumatic) or a pathological mechanism (metabolic or toxic) that can be observed in the clinical context. Most of the pathophysiological hypothesis have been proposed on the basis of studies using these models. However, their clinical relevance and significance (notably those consisting of complete nervous section) have been questioned. Indeed, such nervous lesions induce behavioral changes in animals (i.e. autotomy) which are very different from the symptoms observed in the patients. Such a discrepancy prompted the development of new models which can be considered as ?symptomatic?. These models consisting of incomplete peripheral nerve lesions (e.g. loose ligature of the sciatic nerve) do not reproduce a lesion or a mechanism that can be observed in the clinic, but the behavioral changes in animals can be compared to those observed in the patients. Numerous pharmacological studies have been performed with these models which allow to evaluate evoked pains (i.e. allodynia and hyperalgesia). However, their predictive value and clinical significance can also be questioned. Indeed, the results of the pharmacological studies were very different from those observed in the patients. It is suggested that these models might correspond to one or several subgroups of patients. However, new experimental and clinical studies are needed to determine the clinical relevance of the results obtained in animals studies.

Texte présenté lors du Congrès SFD-SOFRED des 15–17 juin 2000     

Increase of plasma tissue-plasminogen activator antigen levels after induced abortion

We previously reported that plasma thrombotic activity is transiently increased immediately after induced abortion. However, changes in the fibrinolytic system have not vet been studied. Plasma tissue-plasminogen activator (t-PA) antigen levels were studied before and after abortion induced during the first trimester of pregnancy. Compared with the preoperative level (1.68 ± 0.15 ng/ml), t-PA level was significantly increased (2.78 ± 0.55 ng/ml, p<0.01) 15 min after the induced abortion, while it almost returned to the preoperative values (2.09 ± 0.40 ng/ml) 2h later. This finding suggests that fibrinolytic activity is transiently increased immediately after the induced abortion, acting as a defense mechanism against thrombosis.     

In vitro Infection with hiv of antigen-specific t cell clones derived from hiv-seronegative individuals. effects on cytokine production and helper function

Three human T cell clones (TCC) specific for purified protein derivative of Mycobacterium tuberculosis were incubated in the presence of polybrene and phytohemagglutinin with irradiated mononuclear cells from one individual exhibiting seropositivity for human immunodeficiency virus (HIV) and high levels of circulating p24 antigen. After three weeks, TCC showed HIV integration in their DNA, as shown by polymerase chain reaction analysis and Southern blot technique. All the three HIV-infected TCC maintained their ability to recognize the specific antigen, even if their proliferative ability was reduced. The ability of the HIV-infected TCC to produce IL-2, IL-4 and IFN-_y in response to phorbol myristate acetate plus anti-CD3 monoclonal antibody was decreased, whereas their ability to produce TNF-α was unaffected or even enhanced. Two our. of the three HIV-infected TCC showed the ability to provide helper function for polyclonal immunoglobulin production when cocukured with autologous B cells in the absence of any stimulant. These data suggest that in vitro infection of normal human TCC may provide a useful model for the study of immunological alterations induced by HIV. This work was supported by grants from theConsiglio Nazionale delle Ricerche (CNR), theMinistero della Sanità, Istituto Superiore di Sanità (contract AI-25372), and theAssociazione Italiana per la Ricerca sul Cancro (AIRC), Roma, Italy. P. Biswas, C. Simonelli and M. Mazzetti were supported by a fellowship of AIRC. M.-P. Piccinni was supported by a fellowship of European Economic Community.     

Zinc in human health and disease

The importance of zinc in human health and disease has been reviewed by reporting data from the recent literature. The role of zinc in human nutrition, general health, skin diseases, acrodermatitis enteropathica, reproductive physiology and pathophysiology, pregnancy, non-insulin-dependent diabetes mellitus as well as atherosclerosis is discussed. The consequences of zinc deficiency and toxicity are also illustrated.     

Intraoperative validation of a new system for invasive continuous cardiac output measurement

Objective  Although bolus thermodilution technique for cardiac output (CO) measurement has widespread acceptance, new systems are currently available. We evaluated a continuous CO system (TruCCOMS, Aortech International Inc.) that operates on the thermal conservation principle and we compared it with the reference standard transit time flow measurement (TTFM). Materials and methods  Nine consecutive cardiac surgery patients were evaluated. After general anesthesia and intubation, a TruCCOMS catheter was percutaneously placed in the pulmonary artery (PA). After median sternotomy and pericardiotomy, a TTFM probe was placed around the main PA. Right ventricular (RV) CO measurements were recorded with both TruCCOMS and TTFM at different times: before cardiopulmonary bypass (CPB) (T0), during weaning from CPB (T1), and prior to sternal closure (T2). Data analysis included paired student t test, Pearson correlation test, and Bland–Altman plotting. Results  TruCCOMS CO values were significantly lower at T0 (TruCCOMS 4.0 ± 1.0 vs. TTFM 4.5 ± 1.0 L/min; P < 0.0001) and T1 (TruCCOMS 3.6 ± 0.5 vs. TTFM 4.2 ± 0.7 L/min; P < 0.0001), and comparable at T2 (TruCCOMS 4.5 ± 0.7 vs. TTFM 4.6 ± 0.8 L/min; P = 0.4). Pearson test showed a significant correlation between TruCCOMS and TTFM CO measurements (RT0 = 0.9, RT1 = 0.8, RT2 = 0.6; P < 0.0001). Bland–Altmann plotting showed a bias of −0.53 ± 0.43 L (−12%) at T0, −0.64 ± 0.43 L (−14.5%) at T1, and −0.1 ± 0.66 L (−0.8%) at T2. Conclusion  Although TruCCOMS may significantly underestimate CO, measurement trends correlate with TTFM. For this reason, a negative trend in RV output should trigger more specific diagnostic procedures.     

Lithium dilution cardiac output measurement in the critically ill patient: determination of precision of the technique

Background  Lithium dilution cardiac output by LiDCO™plus (LiDCO, Cambridge, UK) is a validated methodology for measuring cardiac output. It is used to calibrate a pulse pressure analysis algorithm (PulseCO) for the continuous measurement of subsequent changes in this variable. The variability of measurements, or precision, within patients of lithium dilution cardiac output has not previously been described. Material and methods  Thirty-five hemodynamically stable patients in intensive care, with no significant variability in heart rate, mean arterial pressure or central venous pressure, were recruited. Fifty-three determinations of cardiac output were made, each using four lithium dilution measurement curves performed consecutively within a maximum period of 10 min. The coefficient of variation of the measurements was determined and used to derive the least significant change in cardiac output that this technique could reliably detect. Results  For a single measurement, the coefficient of variation was 8%. This equates to the technique being able to detect a change (least significant change) between two measurements of 24%. Averaging two lithium dilution measurements improved the coefficient of variation to 6% with a least significant change of 17%. Using the average of three curves reduced the coefficient of variation to 5% with a least significant change of 14%. Conclusions  To achieve a good precision with this technique, three lithium dilution measurements should be averaged. This will allow changes in cardiac output of more than 14% to be reliably detected. The understanding of the precision of this technique allows the user to know when a real change has happened to their patient. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Preliminary data was presented at the Bruxelles ISICEM conference in 2007.     

A Golgi-Cox study of the hypoglossal nucleus of ‘wobbler’ and normal mice

Morphological studies on the hypoglossal nucleus of ‘wobbler’ and control mice were carried out using the Golgi-Cox technique. In ‘wobbler’ mice, soma and dendrites of degenerating neurons were swollen and less darkly stained when compared with normal neurons; in addition, their membrane structure was disrupted. Neurons could not be distinguished by their shape, as they varied gready. Using dendritic directional projections, neurons were classified into four main groups. In the normal mouse, three main classes of neurons are apparent, i.e., large, intermediate and small neurons measuring on the average 25, 16 and 9.5 μ, respectively. In the ‘wobbler’ sections, about 11 degenerating neurons with diameters ranging from 35 to 50 μ were clearly identified.     

Assessing Eating Disorder Thoughts and Behaviors: The Development and Preliminary Evaluation of Two Questionnaires

This paper describes the development of two measures. The first is designed to assess eating disorder-related automatic thoughts; the second is designed to assess a wide range of eating disorder-related behaviors. Principal components analysis identified three dimensions of thoughts: positive thoughts about eating, negative thoughts about eating, and permissive thoughts. Principal components analysis also identified six dimensions of behavior related to: shape and weight, bingeing, dieting, food, eating, and overeating. Both measures possess promising psychometric properties, including good construct and criterion-related validity. Both successfully discriminated eating disorder patients from dieting and non-dieting groups. The two measures may be useful additions to those currently available to researchers (and clinicians) interested in eating disorders.

D-Sorbitol plasma disappearance rate: An index to evaluate changes in liver circulation

The hepatic clearance of D-sorbitol was proven to be a reliable parameter for evaluating the functional liver plasma flow. Twenty-five normal subjects and 50 cirrhotic patients were studied in order to assess if the measure of the plasma disappearance rate of sorbitol can be used as a simpler procedure to evaluate changes in liver perfusion and to predict modifications of drug bioavailability due to circulatory events. The plasma disappearance rate was calculated between 10 and 20 min after intravenous administration of a 2-g dose because in this time interval plasma levels were in the optimum range for the chemical assay, and the plasma concentration/time curve fitted a decreasing exponential function. Plasma disappearance rate values were found to correlate significantly (r = 0.666, p<0.001) with sorbitol hepatic clearance, as calculated after the 2-h test. The test had a good day-to-day reproducibility both in normal subjects and cirrhotic patients. In 5 patients submitted to surgical side-to-side portacaval shunt, decreases of plasma disappearance rate and sorbitol hepatic clearance showed no significant difference. Mean values (± SD) of D-sorbitol plasma disappearance rate were 0.048 ± 0.014 min^-1 in cirrhotic patients, and 0.081 ± 0.014 min-¹ in normal subjects (p<0.001).     

Low Levels of Prothrombin Time (INR) and Platelets Do Not Increase the Risk of Significant Bleeding when Placing Central Venous Catheters*

Abstract Background and Purpose:   Central venous catheters are frequently placed in intensive care medicine for multiple indications. The risk of severe bleeding after cannulation is considered to be increased in patients with abnormal coagulation, common in critically ill patients. Patients and Methods:   This open prospective trial, performed at two medical intensive care units and one hematology intermediate care ward, investigated whether insertion of a central venous catheter in patients with coagulopathy (prothrombin time ≤ 50% [International Normalized Ratio, INR, ≥ 1.5] and/or platelets ≤ 50 × 10⁹/l) bears an increased risk of bleeding. Results:   In 196 patients with and without severe disorders of hemostasis, no significant difference in decrease of hemoglobin after catheter placement was observed. In addition, no correlation between a significant drop in hemoglobin and increased levels of creatinine or urea was seen. Mechanical complications were similar in frequency compared to previous publications. Conclusion:   These findings demonstrate that coagulation disorders with altered prothrombin time (INR) or platelets do not increase the risk of significant bleeding when inserting a central venous catheter. Therefore, the prophylactic correction of coagulation by transfusion of blood products or coagulation factors is not necessary before central venous catheter insertion. *Trial registration: ClinicalTrials.gov NCT00448188.     

Effets analgésiques des morphiniques et systèmes opioïdergiques dans les douleurs chroniques: confrontation des données cliniques et des données expérimentales chez l’animal

Résumé  En tentant de tirer de l’expérimentation animale des explications rationnelles rendant compte de la sensibilité variée des douleurs chroniques chez l’homme aux effets analgésiques des morphiniques, les auteurs de cette revue sont amenés à constater que l’abondance des données fournies par les modèles animaux est inversement proportionnelle à l’usage clinique des opio?des. Ainsi, alors que les douleurs associées à un cancer sont certainement celles qui bénéficient le plus, et depuis longtemps, d’un traitement morphinique, ce n’est que très récemment que les fondamentalistes se sont avisés de développer des modèles appropriés. Concernant les douleurs neuropathiques, malgré la diversité des conditions expérimentales, les opio?des apparaissent doués d’une efficacité élévée pour réduire les comportements nociceptifs dans la plupart des modèles animaux. II est donc peu satisfaisant, en partant des mécanismes physiopathologiques qui en ont été inférés, en particulier ceux qui impliquent directement, ou indirectement, les systèmes opio?des endogènes, de rendre compte de la morphino-résistance de ces douleurs en clinique, même si celle-cireste controversée et repose sur peu de données objectives. S’agissant enfin des douleurs par excès de nociception, une augmentation de la puissance antalgique des morphiniques a été abondamment constatée dans les modèles animaux de douleur inflammatoire, dans lesquels on observe diverses modifications fonctionnelles des systèmes opio?dergiques. Il est prématuré d’établir quelque lien avec la clinique: de fait, l’évaluation réelle de l’efficacité des opio?des dans les douleurs inflammatoires n’a pas fait l’objet d’études spécifiques.

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Summary  Chronic pain symptoms respond to opioid drugs with varying sensitivity. Interestingly, body of data arising from animal models is inversely proportional to the clinical use of opioids. Thus, whereas cancer patients certainly benefit from a long time opioid therapy to relief pain, appropriate experimental models were only recently developed. On the other hand, animal models of neuropathic pain have been around for a long time and opioids appear to have a high efficacy for reducing nociceptive behaviour in most of them. Therefore, it is hard to explain the poor efficacy of opioids for relief of neuropathic pain in humans. With regard to inflammatory pain, an enhancement of the analgesic potency of opioids has been largely established in animal models of chronic inflammatory pain. Any link with clinical data appears to be premature because no specific study has been performed on the efficacy of opioids for treating inflammatory pain.

Texte présenté lors du Congrès SFD-SOFRED des 15–17 juin 2000.