Evaluation of four automated high-sensitivity C-reactive protein methods: implications for clinical and epidemiological applications

BACKGROUND: C-reactive protein (CRP) can provide prognostic information about the risk of developing atherosclerotic complications in apparently healthy patients. This new clinical application requires quantification of CRP concentrations below those traditionally measured in the clinical laboratory. METHODS: The Dade Behring BN II, the Abbott IMx, the Diagnostic Products Corporation IMMULITE, and the Beckman Coulter IMMAGE are four automated analyzers with high-sensitivity CRP (hs-CRP) methods. We evaluated these assays for precision, linearity, and comparability with samples from 322 apparently healthy blood donors. RESULTS: The imprecision (CV) of the BN II, IMx, IMMULITE, and IMMAGE methods was < or = 7.6%, < or = 12%, < or = 9.8%, and < or = 9.7% at 3.5 mg/L, respectively. The BN II, IMx, IMMULITE, and IMMAGE methods were linear down to < or = 0.30, < or = 0.32, < or = 0.85, and 2.26 mg/L, respectively. CRP concentrations demarcating each quartile in a healthy population were method dependent. The IMx method gave results comparable to the BN II method for values in the reference interval. The IMMULITE method had a positive intercept compared with the BN II method. The IMMAGE method demonstrated more scatter and a positive intercept compared with the BN II method, which may reflect the fact that it is a less sensitive assay. CONCLUSIONS: The four hs-CRP methods exhibited differences in results for a healthy population. Additional standardization efforts are required to ensure that hs-CRP results can be related to large-scale epidemiologic studies.     

Comparison of 3 automated assays for C-reactive protein in end-stage renal disease: clinical and epidemiological implications

Chronic inflammation has been repeatedly reported in individuals undergoing hemodialysis. C-reactive protein (CRP) is considered a marker of chronic inflammation, as well as a mediator of the atherosclerotic process. Clinical and epidemiologic studies are based on plasma values obtained with the use of various automated methods. Our aim was to test 3 commercially available methods and compare the values obtained with the use of these tests in a population of individuals undergoing hemodialysis. We compared the following methods: immunoturbidimetry (AU2700 biochemistry analyzer; Olympus, Rungis, France) laser nephelometry (Behring Diagnostics, Marburg, Germany), and nephelometry (Beckman Instruments, Fullerton, Calif. The 3 methods were used in 3 different centers: Montpellier, France; and Pisa and Turin, Italy, respectively. We prepared samples for the estimation of imprecision values (ie, coefficient of variation [CV]) from the plasma of normal patients by adding purified C-reactive protein at concentrations ranging from 2.6 to 180 mg/L for intraassay variation and concentrations of 0, 1, 2, 3, 5, 10, 20, 50, 100, 150, and 180 mg/L for interassay variation. Intraassay imprecision was determined with the use of 10 replicate analyses on the same sample of the same day. We assessed interassay imprecision using the same sample, divided into aliquots and measured on 5 consecutive days. Agreement between methods was assessed on predialysis serum samples collected from patients with stable chronic kidney disease who were undergoing long-term hemodialysis at the 3 different centers (Montpellier,192; Pisa, 56; Turin,98). Serum was separated from the red cells and stored in 3 aliquots at -70 degrees C until it could be analyzed. Samples were thawed only once, circulated among the 3 centers, and each tested with all 3 of the methods. The Beckman method yielded the most precise results, with intraassay CVs ranging from 1 to 2 and interassay CVs ranging from 1 to 4. The Behring method was the least precise, with intraassay and interassay CVs ranging from 12 to 15 and 7 to 16, respectively. The results of the Olympus method fell between those of the other 2 methods. Agreement between the results of the Olympus and Behring methods was satisfactorily. The Beckman and Olympus methods yielded, on average, similar results over the entire range of CRP values. We detected significant disagreement between the Beckman method and the other 2 methods, obtaining results 10 to 100 times lower with the Beckman method. This became evident in terms of kappa-statistics. Our findings emphasize the need for careful assessment of the methods used to detect CRP in serum samples. Failure to do so may ultimately have a negative impact on the real relevance of CRP as a marker and on the role of chronic implication particularly in epidemiologic studies.     

Evaluation of nine automated high-sensitivity C-reactive protein methods: implications for clinical and epidemiological applications. Part 2

BACKGROUND: C-Reactive protein (CRP) can provide prognostic information about risk of future coronary events in apparently healthy subjects. This application requires higher sensitivity assays than have traditionally been available in the clinical laboratory. METHODS: Nine high-sensitivity CRP (hs-CRP) methods from Dade Behring, Daiichi, Denka Seiken, Diagnostic Products Corporation, Iatron, Kamiya, Olympus, Roche, and Wako were evaluated for limit of detection, linearity, precision, prozone effect, and comparability with samples from 388 apparently healthy individuals. RESULTS: All methods had limits of detection that were lower than the manufacturers' claimed limit of quantification except for the Kamiya, Roche, and Wako methods. All methods were linear at 0.3-10 mg/L. The Diagnostic Products Corporation, Kamiya, Olympus, and Wako methods had imprecision (CVs) >10% at 0.15 mg/L. The Iatron, Olympus, and Wako methods demonstrated prozone effects at hs-CRP concentrations of 12, 206, and 117 mg/L, respectively. hs-CRP concentrations demarcating each quartile in a healthy population were method-dependent. Ninety-two to 95% of subjects were classified into the same quartile of hs-CRP established by the Dade Behring method by the Denka Seiken, Diagnostic Products Corporation, Iatron, and Wako methods. In contrast, 68-77% of subjects were classified into the same quartile by the Daiichi, Kamiya, Olympus, and Roche methods. No subject varied by more than one quartile by any method. CONCLUSIONS: Four of the nine examined hs-CRP methods classified apparently healthy subjects into quartiles of hs-CRP similar to the classifications assigned by the comparison method. Additional standardization efforts are required because an individual patient's results will be interpreted using population-based cutpoints.     

Circulating soluble adhesion molecules ICAM-1 and VCAM-1 and their association with clinical outcome, troponin T and C-reactive protein in patients with acute coronary syndromes

OBJECTIVES: The aim of this study was to compare concentrations of soluble intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) in patients with coronary artery disease and healthy control and to evaluate the usefulness of the inflammatory markers as predictors of adverse prognosis in patients with acute coronary syndromes (ACS). DESIGN AND METHODS: ELISA was used to measure sICAM-1 and sVCAM-1 levels in 75 patients with ACS, 36 patients with stable angina pectoris (SAP) and 25 healthy subjects. hsCRP was measured with immunoturbidimetric assay, cardiac troponin T-with electrochemiluminescence immunoassay. RESULTS: All soluble ICAM-1 and VCAM-1 significantly discriminated between patients with ACS and SAP (p=0.014 and 0.05, respectively) and control subjects (p<0.001 and 0.05). During the 6-month follow-up of the patients with ACS, there were 28 major cardiac events (37.3%). The odds ratio associated with the highest value of sVCAM-1 was 4.62 (95% CI 1.8-11.4, p=0.0009) without adjustment and remained significantly elevated after adjustment for cTnT (RR 3.93, 1.5-10, p=0.04) and hsCRP (RR 2.22, 0.8-5.7, p=0.05). In contrast, an elevated level of sICAM-1 was not associated with future coronary risk after adjustment for cTnT and hsCRP. CONCLUSIONS: In patients with acute coronary syndromes, VCAM-1 serum levels powerfully predict an increased risk for subsequent cardiovascular events and extend the prognostic information gained from traditional biochemical markers.     

Influence of single low-density lipoprotein apheresis on the adhesion molecules soluble vascular cellular adhesion molecule-1, soluble intercellular adhesion molecule-1, and P-selectin.

The aim of our study was to investigate the influence of single low-density lipoprotein apheresis (heparin extracorporeal low-density lipoprotein precipitation [HELP]procedure) on plasma concentrations of soluble adhesion molecules (sAMs) such as soluble vascular cellular adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and P-selectin in patients with familial heterozygous hypercholesterolemia and documented coronary artery disease enrolled in a chronic weekly HELP apheresis. Before HELP apheresis, the mean plasma concentration of sVCAM-1 was 515 +/- 119 ng/ml, 204 +/- 58 ng/ml for sICAM-1, and 112 +/- 45 ng/ml for P-selectin. After single HELP apheresis, plasma concentrations of sAM declined significantly by 32 +/- 7%, 18 +/- 15%, and 33 +/- 25% for sVCAM- 1,sICAM-1 and P-selectin, respectively. After a 1 week interval, sAM concentrations rose to approximately the initial values. The concentrations of all sAMs studied were significantly lower in the plasma leaving than entering the filter. Due to filtration, the decline in plasma level of sVCAM-1, sICAM-1, and P-selectin was 62 +/- 19%, 51 +/- 39%, and 67 +/- 22%, respectively. In addition to lipid reduction, single HELP apheresis significantly lowers plasma concentrations of sVCAM-1, sICAM-1, and P-selectin.     

C-reactive protein and anemia: implications for patients on dialysis.

C-reactive protein (CRP) is an acute-phase reactant protein that increases significantly in the presence of intercurrent (concurrent) events such as infectious and inflammatory processes. Data indicate that CRP levels correlate with anemia parameters, higher levels being associated with an increased comorbidity burden, lower hemoglobin (Hb) levels, and higher Epoetin alfa dose requirements. This article explores the use of CRP monitoring in patients on dialysis, and the relationship to anemia outcomes.     

Kinetics of soluble TNF-receptors and soluble adhesion molecules ICAM-1, E-selectin and VCAM-1 under systemic rhTNFα therapy

Cytostatic as well as cytotoxic effects of tumour necrosis factor alpha (TNF-α) therapy have been shown in vitro and in experimental in vivo models. Nevertheless, the mechanism of anti-tumour activity in humans in vivo remains unclear. To determine the role of the vascular lining endothelial cells as important mediators of several immunological interactions, we investigated changes in the levels of the soluble endothelial cell adhesion molecules intercellular adhesion molecule 1, E-selectin and vascular cell adhesion molecule 1 as well as of soluble TNF receptors I and II during systemic therapy with recombinant human rhTNF-α (rhTNF-α). All tests were performed by enzyme-linked immunosorbent assays (ELISAs). The clinical efficacy of the intravenous rhTNF-α therapy was poor. Only one patient with isolated intra-arterial limb perfusion had a delayed, marked, but only temporary necrosis of tumour cells. In contrast, we found a marked, significant and (during therapy) undulating augmented increase in the levels of soluble adhesion molecules as well as of the soluble TNF receptors. Taken together, these data support the hypothesis that a sufficient tumour-specific cellular immunity is required to achieve a clinically apparent efficacy of systemic rhTNF-α therapy in addition to cytokine-dependent inducible activation mechanisms. In this context, the vascular lining endothelial cells might play an important role as mediators of the complex immunological antitumoral activity.     

Poor asthma control in children: evidence from epidemiological surveys and implications for clinical practice

The objectives of this study is to compile current knowledge about asthma control in children in relation to goals proposed in international guidelines, to elucidate the factors associated with insufficient asthma control and to address the implications for clinical practice. Review of recent worldwide large population epidemiological surveys and clinical asthma studies of more than 20,000 children are the methods used in this study. The studies report high frequencies of sleep disturbances, emergency visits, school absence and limitations of physical activity due to asthma. Only a small percentage of children with asthma reach the goals of good asthma control set out by Global Initiative for Asthma (GINA). There is evidence of underuse of inhaled corticosteroids even in children with moderate or severe persistent asthma and over-reliance on short-acting beta(2)-agonist rescue medication. Both parents and physicians generally overestimate asthma control and have low expectations about the level of achievable control. Many children with asthma are not being managed in accordance with guideline recommendations, and asthma management practices vary widely between countries. Asthma control falls short of guideline recommendations in large proportions of children with asthma worldwide. Simple methods for assessing asthma control in clinical practice are needed. Treatment goals based on raised expectations should be established in partnership with the asthmatic child and the parents. Effective anti-inflammatory treatment should be used more frequently, and patients should be reviewed regularly.     

强化降脂治疗对不稳定型心绞痛患者血清高敏C反应蛋白、可溶性血管细胞黏附分子1水平的影响

目的探讨大剂量氟伐他汀对不稳定型心绞痛患者血清炎症因子高敏C反应蛋白（hsCRP）、可溶性血管细胞黏附分子1（sVCAM-1）水平的影响。方法将不稳定型心绞痛患者70例随机分为两组,每组各35例。A组在常规治疗基础上给予氟伐他汀40mg/d,B组在常规治疗基础上给予氟伐他汀80mg/d,用酶联免疫吸附测定法检测治疗前后血清hsCRP、sVCAM-1水平,并检测其他临床指标。结果治疗2周后,两组总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）均较治疗前降低（P〈0.05）,但组间比较差异无统计学意义（P〉0.05）;两组治疗后hsCRP、sVCAM-1浓度均比治疗前降低（P〈0.01）,治疗后两组比较差异有统计学意义（P〈0.01）,治疗后A组和B组分别为hsCRP（10.52±1.76）mg/L vs（7.79±1.53）mg/L;sVCAM-1（441.18±87.06）μg/L vs（347.91±94.25）μg/L;hsCRP、sVCAM-1下降与LDL-C、TC下降无相关性（P〉0.05）。结论强化降脂治疗能明显抑制不稳定型心绞痛患者的炎症反应,降低血清hsCRP和sVCAM-1水平,氟伐他汀的抗炎作用独立于降脂作用以外。     

冠心病患者血清C-反应蛋白和可溶性白细胞介素-6变化及临床意义

目的探讨冠心病患者血清C-反应蛋白(CRP)和可溶性白细胞介素-6(IL-6)的变化及临床意义。方法190例冠心病患者,按临床诊断分为3组:急性心肌梗死组(AMI)70例、不稳定性心绞痛组(UA)55例、稳定性心绞痛组(SA)65例和对照组80例。用酶联免疫吸附试验检测各组血清CRP和可溶性IL-6的水平,并比较各组间的差异。结果AMI组、UA组的血清CRP和可溶性IL-6水平明显高于对照组和SA组,并有显著性差异(P<0.01)。结论冠心病患者血清CRP及可溶性IL-6水平明显升高,可能与疾病的严重程度相关,两者的检铡有助于冠心病的诊断及UA和SA的鉴别诊断。     

Serum C-reactive protein in elderly men and women: association with mortality, morbidity and various biochemical values

OBJECTIVE: The primary aim of this study was to define the distribution and the prognostic value of serum C-reactive protein (s-CRP) measured by a high-sensitivity method in elderly subjects of both genders with special reference to the distribution below 10 mg/l. As a secondary aim, a possible gender difference of s-CRP was examined. MATERIAL AND METHODS: Baseline s-CRP was described in a population-based sample of opposite-sex, twin-pairs (197 F, 189 M available for blood-sampling) aged 71-80 years (mean age 74.5 years), considering mortality through the next 4 years, morbidity (myocardial infarction, angina pectoris, congestive heart failure, arterial hypertension, venous thromboembolism, stroke, diabetes, gout, psoriasis, rheumatoid arthritis) before and after blood sampling, biochemical values (serum levels of urate, urea, ApoA1, ApoB, folate, FSH, LH, oestradiol, progesterone, testosterone, cortisol) and anthropometric measurements (body mass index (BMI), circumference of waist, buttocks and hips). RESULTS: The level of s-CRP did not deviate substantially from what has been reported for younger subjects. Higher values indicated an increased risk of cardiovascular morbidity and diabetes in women but not in men. The s-CRP level was associated with serum levels of urate, progesterone, folate, ApoA1, ApoB and the quotient ApoB/ApoA1 as well as with BMI and waist circumference. CONCLUSIONS: For the 71-80 years age group, s-CRP below the 80th percentile (4.3 mg/l) seems to have prognostic capacity mainly in women. The highest association with mortality as well as with cardiovascular diseases, diabetes and rheumatoid arthritis is found for s-CRP above 10 mg/l, which is the arbitrary lower level for the earlier routine low-sensitivity s-CRP methods. The association of s-CRP with serum urate, folate and the ApoB/ApoA1 quotient should be considered.     

Preanalytic and analytic sources of variations in C-reactive protein measurement: implications for cardiovascular disease risk assessment

BACKGROUND: C-reactive protein (CRP) is a widely recognized indicator of inflammation and is known to play an important role in atherogenesis. Recent prospective studies have demonstrated that increased CRP concentrations within the reference interval are a strong predictor of myocardial infarction, stroke, sudden cardiac death, and peripheral vascular disease in apparently healthy adults. On the basis of available evidence, the American Heart Association and the CDC have issued guidelines for the utility of CRP in the primary prevention of coronary heart disease and in patients with stable coronary disease or acute coronary syndromes. Nevertheless, there remains considerable work to optimize the utility of this marker for risk assessment. ISSUES: Most traditional CRP tests designed to monitor acute and chronic inflammation have inadequate sensitivity for risk stratification of coronary disease. Thus, manufacturers have had to develop tests with higher sensitivity. Because an individual's CRP concentration will be interpreted according to fixed cut-points, issues related to the preanalytic and analytic components of CRP measurement must be considered and standardized where possible to avoid potential misclassification of cardiovascular risk. CONCLUSIONS: Efforts to define performance criteria for high-sensitivity CRP applications coupled with growing awareness of the physiologic aspects of CRP most likely will lead to refinements in standardization, improved performance in quality-assessment schemes, and enhanced risk prediction.     

感染性心内膜炎术后可溶性细胞间黏附分子1、可溶性P-选择素和凝血功能的表达及其临床意义

目的探讨细菌性感染性心内膜炎(infectious endocarditis,IE)术后辅助性T细胞17(T helper cell 17,Th17)相关因子、可溶性细胞间黏附分子1(soluble intercellular adhesion molecule-1,sICAM-1)、凝血功能的表达及其意义。方法选取2016年12月至2018年12月首都医科大学附属北京安贞医院心脏外科手术治疗且符合纳入标准的IE患者进行前瞻性分析,38例IE患者作为观察组;选取同期健康体检者30名为对照组。采用双抗夹心酶联免疫吸附(enzyme-linked immunosorbent assay,ELISA)法测定两组血清Th17相关因子[白细胞介素1β(interleukin-1β,IL-1β)、白细胞介素6(interleukin-6,IL-6)、白细胞介素17(interleukin-17,IL-17)及白细胞介素21(interleukin-21,IL-21)]、sICAM-1及凝血功能指标[可溶性P-选择素(P selectin,sP-SLT)]浓度,并对两组间相关指标的浓度差异进行统计学分析比较。结果观察组患者术前血清IL-1β、IL-6、IL-17及IL-21浓度[(29.88±6.49)、(14.89±3.31)、(21.89±3.01)、(563.26±67.36)ng/L]显著高于对照组[(16.56±4.11)、(7.52±2.34)、(12.91±1.01)、(423.38±56.49)ng/L],差异有统计学意义(t值分别为10.30、10.74、17.20、49.48,P均<0.05)。观察组术前血清sICAM-1、sP-SLT浓度[(1247.57(581.39,1794.66)μg/L、(60.29±6.61)mg/L]显著高于对照组[(837.28(405.68,954.47)μg/L、(27.37±5.56)mg/L],差异有统计学意义(Z=12.37、t=22.30,P均<0.05)。术后感染性心内膜炎患者血清IL-1β、IL-6、IL-17及IL-21浓度[(16.19±4.07)、(7.73±2.40)、(13.83±0.94)、(425.33±52.12)ng/L]较术前[(29.88±6.49)、(14.89±2.31)、(21.89±3.01)、(563.26±67.36)ng/L]均显著降低,差异有统计学意义(t值分别为11.02、13.25、15.76、9.98,P均<0.05)。术后感染性心内膜炎患者血清sICAM-1、sP-SLT1浓度[(901.46(472.15,1276.58)μg/L、(30.70±5.31)mg/L]较术前[(1057.26±463.06)μg/L、(60.29±6.61)mg/L]显著降低,差异有统计学意义(Z=11.16、t=21.51,P均<0.05)。结论在IE患者中Th17相关因子、sICAM-1及sP-SLT呈高浓度表达,同时术后上述因子浓度降低,提示以上因子可能作为辅助诊断、评估IE患者病情及预后的相关因子。     

老年慢性阻塞性肺疾病急性加重期血清降钙素原／C-反应蛋白检测的临床意义

目的探讨血清降钙素原（PCT）与C-反应蛋白（CRP）在老年慢性阻塞性肺疾病（COPD）急性加重期水平发生变化的临床意义。方法测定52例老年COPD急性加重期、50例健康对照组研究对象的血清PCT、CRP指标,并比较临床治疗前后老年COPD患者两项指标水平变化情况。结果老年COPD急性加重期患者血清PCT（5.871.01）和CRP（39.647.15）水平高于健康对照组PCT（0.340.12）和CRP（1.510.16）,差异有统计学意义（P〈0.01）;临床治疗后老年COPD患者病情得到缓解,PCT和CRP水平下降;老年COPD急性加重期两项指标阳性检出率高（P〈0.05）。结论血清TCT、CRP是反映老年COPD急性加重期的辅助诊断指标。     

白血病患者可溶性耐药相关钙结合蛋白基因的表达及其临床意义

目的：探讨白血病患者可溶性耐药相关钙结合蛋白（Sorcin)基因的表达及其与临床耐药和疗效的关系。方法：应用半定量RT－PCR检测95例急性白血病患者、27例非白血病患者和健康人的Sorcin基因表达水平，并分析了Sorcin基因表达的临床意义。结果：白血病患者Sorcin基因表达高于对照组，差异有显著性（P＜0．001）；急性髓系白血病（AML）复发难治组高于初诊组和完全缓解（CR）组；临床耐药组Sorcin基因表达显著高于非临床耐药性（P＜0．001）；Sorcin基因阳性表达的CR率为20．0％，Sorcin基因阴性表达的CR率为80．0％，差异有显著性（P＜0．001）；AML各亚型Sorcin基因过度表达存在差异，以M5的阳性表达率最高。结论：Sorcin基因过度表达与白血病患者临床耐药密切相关，是影响预后的重要因素，可作为检测临床耐药和判断预后的指标之一。     

Relation between soluble adhesion molecules and insulin sensitivity in type 2 diabetic individuals: role of adipose tissue.

OBJECTIVE: The purpose of this study was to explore the relation between insulin resistance and plasma levels of soluble adhesion molecules and to examine the effects of acute hyperinsulinemia on these molecules in type 2 diabetic individuals. RESEARCH DESIGN AND METHODS: Intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E- and P-selectin plasma concentrations were measured in 36 nonobese type 2 diabetic patients without cardiovascular disease and in 7 healthy subjects. Insulin sensitivity was assessed by a 4-h euglycemic ( approximately 5 mmol/l)-hyperinsulinemic ( approximately 300 pmol/l) clamp performed in combination with [(3)H]3-D-glucose infusion. RESULTS: Diabetic subjects were insulin resistant but did not show plasma concentrations of adhesion molecules that were significantly higher than control subjects. In diabetic subjects, plasma ICAM-1 and E-selectin were negatively correlated with total glucose disposal during the insulin clamp (r = -0.432, P < 0.01; and r = -0.375, P < 0.05, respectively), whereas plasma VCAM-1 and P-selectin were not. Plasma ICAM-1 as well as E- and P-selectin were positively correlated with BMI, total body fat (TBF), and waist girth (P < 0.05-0.001). In multiple regression analyses, the relation of plasma ICAM-1 and E-selectin with insulin sensitivity was lost after adjustment for potential confounders, including HbA(1c), blood pressure, and/or LDL cholesterol. In these analyses, BMI was the only independent predictor of plasma ICAM-1 (R(2) = 0.244, P < 0.002), whereas TBF was the only independent predictor of plasma E-selectin (R(2) = 0.202, P = 0.01). The 4-h insulin infusion during the glucose clamp did not significantly change plasma levels of adhesion molecules. CONCLUSIONS: Overall adiposity, rather than insulin resistance, may be a determinant of plasma levels of ICAM-1 and E-selectin in type 2 diabetic individuals. In these patients, acute hyperinsulinemia does not exert any significant effect on plasma adhesion molecules. These findings support the possibility that adipose tissue releases one or more factors that may adversely affect endothelial function on one hand and insulin sensitivity on the other.     

The neurochemistry of central pain: evidence from clinical studies,hypothesis and therapeutic implications

Recent evidence suggests that central pain, i.e., pain due to central nervous system damage, may be due to a deranged neurotransmission between the sensory thalamus and sensory cortical areas. Central pain can be controlled either by opposing glutamate neurotransmission or potentiating GABAergic transmission. It is speculated that a relative hypofunction of the GABAergic inhibition both at thalamic and cortical levels leads to a sectorial excitatory hypertonus in those same areas. A blend of the two should mark each patient. A pharmacological dissection approach is provided that should optimize the treatment, up to now globally poor, of central pain.