Rehabilitation therapy in chronic low back pain.
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Biomedical subjects
Publications and source records attributed to S Poiraudeau.
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Intervertebral disc cells can be cultured in vitro. Several culturing systems in a mechanically active environment have been developed to study the relationship between mechanical stimulations and biochemical events. The aim of this study was to assess the phenotype of rabbit intervertebral disc cells from the anulus fibrosus (AF) region cultured on flexible substrate before and after application of cyclic tensile stretch (CTS) and to control culture conditions during application of CTS. CTS was applied with a pressure-operated instrument, inducing the deformation of flexible-bottomed culture plates (Flexercell) at 20% and 5% stretch, at a frequency of 1 Hz, during 30 minutes to 24 hours. A significant decrease in culture medium volume and temperature was observed (52% and 2.1 degrees C at 20% stretch and 24 hours' application of CTS). These phenomena were inhibited by adding culture medium around culture wells and by a culture medium temperature control system. Like AF cells cultured in plastic wells, AF cells cultured on flexible substrate expressed collagen type II, but collagen type I mRNA was not detected. In both culture conditions, neosynthesized proteoglycans had the same aggregating properties. CTS at 20% stretch during 12 hours did not induce cell detachment from the substrate and did not modify aggregating properties of neosynthesized proteoglycans; AF cells continued to express collagen type II but not collagen type I mRNA. In conclusion, the Flexercell system appears to be appropriate for studying, at the cellular level, the metabolic responses to CTS.
STUDY DESIGN: Anulus fibrosus cells from rabbits were grown in primary culture 1) to study their ability to produce prostaglandin E2 and Type II phospholipase A2, and to express stromelysin-1 messenger ribonucleic acid; and 2) to study the effect of interleukin 1 beta on this production and on proteoglycan aggregation. OBJECTIVES: To investigate the potency of anulus fibrosus cells to respond to interleukin 1 beta by producing degradative and inflammatory agents as compared with the potency of articular chondrocytes in the same animal. SUMMARY OF BACKGROUND DATA: Interleukin 1 beta has been implicated in the degradation of intervertebral discs. The way anulus fibrosus cells differ from articular chondrocytes in their responses to interleukin 1 beta remains to be established. METHODS: Anulus fibrosus cells and articular chondrocytes were obtained from young rabbits, grown in primary culture, and incubated with interleukin 1 beta. The newly synthesized proteoglycan was measured by labeling with [35S]-sulfate. Proteoglycan aggregation was analyzed by the elution profile on Sepharose 2B columns. The contents of collagen Type II and stromelysin-1 messenger ribonucleic acid were assessed by Northern blot analysis. The Type II phospholipase A2 activity was measured using a fluorometric substrate. Prostaglandin E2 production was evaluated by radioimmunoassay. RESULTS: Anulus fibrosus cells had 2.5-fold less Type II collagen messenger ribonucleic acid than articular chondrocytes, and interleukin 1 beta had no significant effect on this. Anulus fibrosus cells synthesized and secreted four-fold less proteoglycan than articular chondrocytes. Interleukin 1 beta reduced the anulus fibrosus content of total [35S]-sulfated proteoglycan by 35% (P < 0.01), and that of articular cells by 41% and decreased proteoglycan aggregation. Interleukin 1 beta induced the production of stromelysin-1 messenger ribonucleic acid in both cell types. The stromelysin-1 messenger ribonucleic acid content of anulus fibrosus cells was one half that of articular cells. Interleukin 1 beta increased the production of prostaglandin E2 and caused a dose-dependent secretion of Type II phospholipase A2 activity in both cell types. Its effect was 2.5-fold lower in anulus fibrosus cells than in articular chondrocytes. CONCLUSION: Anulus fibrosus cells can be stimulated by interleukin 1 beta to produce factors implicated in local degradative and inflammatory processes. This production is associated with decreased proteoglycan aggregation. Anulus fibrosus cells respond slightly less well to interleukin 1 beta in vitro than do articular cells.
STUDY DESIGN: Intervertebral disc cells were extracted from the surrounding matrix, and their metabolic activities and phenotypes were studied. OBJECTIVES: To compare the metabolic activities and phenotypes of cell populations extracted from the intervertebral discs of young rabbits with those of articular and growth plate chondrocytes from the same animals. SUMMARY OF BACKGROUND DATA: The phenotype of intervertebral disc cells has been poorly studied and still is debated. METHODS: The intervertebral discs as well as articular and vertebral growth plate cartilage of rabbits were digested enzymatically. The morphology of freshly isolated cells was examined. Their contents of collagen II and X mRNAs were determined by Northern blot analysis, and their sulfation activity by 35S-sulfate incorporation as chondrocytic markers. Cells were cultured at high density or low density and grown in primary culture. The stability of their phenotype was monitored by evaluating the collagen I and II mRNA ratio. The proteoglycans newly synthesized by the cells also were quantified, and their elution profile analyzed on Sepharose 2B columns. RESULTS: The anulus fibrosus cells were morphologically undistinguishable from articular chondrocytes. The nucleus pulposus contained mainly large vacuolated cells and a few smaller cells. All freshly extracted cells expressed different levels of collagen II mRNA. Anulus fibrosus and nucleus pulposus cells contained, respectively, 22% and 8% of collagen II mRNA compared with that found in articular or growth plate chondrocytes from the same animal. Only growth plate chondrocytes expressed collagen X. When anulus fibrosus cells were incubated for 48 hours at high density, they had collagen II mRNA contents similar to those of articular and growth plate chondrocytes, but synthesized five to six times fewer sulfated proteoglycans. When seeded at low density, anulus fibrosus cells divided more slowly than articular chondrocytes and incorporated four times fewer 35S-sulfate into proteoglycans. Their collagen II mRNA content was 2.75-fold lower than that of chondrocytes, and the procollagen alpha 1II/alpha 1I mRNA ratio was 3.1 for anulus fibrosus cells and 7 for chondrocytes. No collagen X mRNA was detected. When incubated for 48 hours at high density, the nucleus pulposus giant cells had four times less collagen II mRNA content than cartilage cells but synthesized the same amounts of sulfated proteoglycans. They did not divide during 21 days in culture and still contained collagen II mRNA but no collagen X mRNA. CONCLUSIONS: Findings showed that intervertebral disc cells all express cartilage-specific matrix proteins with quantitative differences, depending on their anatomic situation. It is suggested that anulus fibrosus cells are chondrocytic cells at a different stage of differentiation than articular and growth plate chondrocytes. The phenotype of nucleus pulposus cells still is unclear. They could be chondrocytic or notochordal. A definitive answer to this important question requires differentiating markers of notochordal cells.
STUDY DESIGN: Prospective randomized study to compare the efficacy of facet joint injection with lidocaine and facet joint injection with saline in two groups of patients with low back pain, with and without clinical criteria that were determined in a previous study to implicate the facet joint as the primary source of the pain. OBJECTIVES: To assess the efficacy of single facet joint anesthesia versus placebo (saline injections) and to determine clinical criteria that are predictive of significant relief of LBP after injection. SUMMARY OF BACKGROUND DATA: There is no syndrome that discriminates between lower back pain caused by facet joint and that caused by other structures. Single or double facet joint anesthesia, and single photon emission computed tomography are expensive and time-consuming procedures for selecting patients in controlled clinical trials with large populations. METHODS: Results of a previous study showed that seven clinical characteristics were more frequent in patients who responded to facet joint anesthesia than in those who did not. In the current study, a group of 43 patients with lower back pain who met at least five criteria were compared with 37 patients who met fewer criteria. Patients randomly received injection of either lidocaine or saline into the lower facet joints. The result was considered positive if more than 75% pain relief was determined by visual analog scale. The patient, the radiologist, and the investigator were blinded. An analysis of variance was used to seek an interaction between clinical group effect and injection effect, and logistic regression analysis to select the best set of variables that would be predictive of minimum pain relief of 75% after the injection. RESULTS: There was a significant interaction between clinical group and injection effect (P = 0.003). In patients with back pain, lidocaine provided greater lower-back pain relief than saline (P = 0.01). Lidocaine also-provided greater pain relief in the back pain group than in the nonpain group (P = 0.02). The presence of five among seven variables (age greater than 65 years and pain that was not exacerbated by coughing, not worsened by hyperextension, not worsened by forward flexion, not worsened when rising from flexion, not worsened by extension-rotation, and well-relieved by recumbency), always including the last item, distinguished 92% of patients responding to lidocaine injection and 80% of those not responding in the lidocaine group. CONCLUSIONS: A set of five clinical characteristics can be used in randomized studies to select lower back pain that will be well relieved by facet joint anesthesia. These characteristics should not, however, be considered as definite diagnostic criteria of lower back pain originating from facet joints.
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This study describes the mechanisms involved in the IGF-1 and IGF-2-induced increases in intracellular calcium concentration [Ca2+]i in cultured chondrocytes and the involvement of type 1 IGF receptors. It shows that IGF-1, IGF-2, and insulin increased the cytosolic free calcium concentration [Ca2+]i in a dose-dependent manner, with a plateau from 25 to 100 ng/ml for both IGF-1 and IGF-2 and from 1 to 2 micrograms/ml for insulin. The effect of IGF-1 was twice as great as the one of IGF-2, and the effect of insulin was 40% lower than IGF-1 effect. Two different mechanisms are involved in the intracellular [Ca2+]i increase. 1) IGF-1 and insulin but not IGF-2 involved a Ca2+ influx through voltage-gated calcium channels: pretreatment of the cells by EGTA and verapamil diminished the IGF-1 or insulin-induced [Ca2+]i but did not block the effect of IGF-2. 2) IGF-1, IGF-2, and insulin also induced a Ca2+ mobilization from the endoplasmic reticulum: phospholipase C (PLC) inhibitors, neomycin, or U-73122 partially blocked the intracellular [Ca2+]i increase induced by IGF-1 and insulin and totally inhibited the effect of IGF-2. This Ca2+ mobilization was pertussis toxin (PTX) dependent, suggesting an activation of a PLC coupled to a PTX-sensitive G-protein. Lastly, preincubation of the cells with IGF1 receptor antibodies diminished the IGF-1-induced Ca2+ spike and totally abolished the Ca2+ influx, but did not modify the effect of IGF-2. These results suggest that IGF-1 action on Ca2+ influx involves the IGF1 receptor, while part of IGF-1 and all of IGF-2 Ca2+ mobilization do not implicate this receptor.
This prospective longitudinal study was undertaken to examine the short-term effects (6 months) of estrogen withdrawal on the circulating IGF system. A series of 40 patients suffering from endometriosis was studied before and after a 6-month treatment period with gonadotrophin releasing hormone (GnRH) agonist and calcium, with or without nasal salmon calcitonin. The plasma concentrations of insulin-like growth factor I (IGF-I) and insulin-like growth factor II (IGF-II) were measured by radioimmunoassay and radioreceptor assay respectively. Plasma IGF binding proteins (IGFBPs) were quantified and characterized by ligand blot and immunoblot. In all patients, a secondary hypoestrogenism was observed, including a 4% decrease in lumbar bone mineral density (L-BMD). The plasma IGF-I and IGF-II concentrations increased after treatment (24%, p < 0.0005 and 40%, p < 0.004 respectively), with no significant difference between the treatment groups. There was a positive correlation between plasma IGF-I (but not IGF-II) changes and changes in urinary deoxypyridinoline (r = 0.32, p < 0.05), urinary C telopeptide of type 1 collagen (r = 0.33, p < 0.04) and total plasma alkaline phosphatases (r = 0.33, p < 0.04). No correlation was found between IGF-I and L-BMD changes, while there was a positive correlation between the changes in plasma IGF-II and L-BMD (r = 0.32, p < 0.05). Ligand blot analysis revealed a significant increase in IGF-II binding to a 29-31 kilodalton region where positive staining with specific antibodies to IGFBP-3 or IGFBP-1 was observed. In conclusion, IGF-I and IGF-II plasma concentrations are both increased following a short period of treatment with a GnRH agonist. The changes in individual IGF peptides are differently correlated with changes in markers of bone remodelling and L-BMD.
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Osteoarthritis is mainly characterized by cartilage degradation as a result of series of pathological processus still not well understood. In recent years much interest has centered on the contribution of cytokines to cartilage degradation: characterization of cytokines extracted from normal and pathological articulation, site of production (synoviocytes, chondrocytes, osteoblasts) and their role on the production of proteases, protease inhibitors or other types of molecules implicated in osteoarthritis. Several types of cytokines such as IL 1 beta and TNF alpha, known as proinflammatory factors in rheumatoid arthritis, have been shown to be present in the synovial fluid from osteoarthritic patients. Recent experimental data allow us to better understand the cellular and molecular mechanisms of the cytokines respectively involved into rheumatoid arthritis and osteo-arthritis.
OBJECTIVE: To construct a functional disability scale for the rheumatoid hand and to determine if this scale also assesses functional handicap. METHODS: Outpatients and inpatients with rheumatoid arthritis (RA) according to the ACR criteria answered a set of questions on their daily hand activities. Intrarater and interrater reliability were examined. Criterion referenced validity, and convergent and divergent validities were investigated. Factor analysis followed by varimax rotation was performed. Spearman's (rs) correlation coefficients between 2 quantitative variables were examined. The level of significance was p < 0.05. RESULTS: 96 patients with RA were recruited. The provisional scale had 41 questions. The elimination process left 18 hand activity questions with 6 levels of answers. The intrarater and interrater reliabilities of the scale were 0.97 and 0.96, respectively. Correlation of the scale's total score with visual analog scale (VAS) measure of functional handicap (rs = 0.78) showed good criterion referenced validity. The scale had good convergence with Revel's Functional Index (rs = 0.91) and a moderate relation to the Hand Functional Index (HFI) (rs = 0.58). The scale had a moderate, fair, or no relation to age, morning stiffness, pain measures, and hand swelling. The scale had 3 main factors by factor analysis. An English translation of the scale was validated. CONCLUSION: We have developed a practical functional disability scale for rheumatoid hands that also assesses functional handicap. It has 18 hand activity questions and has been validated in a French population.
OBJECTIVE: To determine the cross sectional and longitudinal reproducibility of various measures used for assessing radiographic knee osteoarthritis (OA) and to compare the sensitivity to change over a one year period of these measures. METHODS: We studied 55 patients referred to hospital with knee OA (clinical and radiographic ACR criteria). Anteroposterior radiographs at baseline and after 12 months were read by methods both qualitative (Kellgren and Lawrence grading scale, joint space narrowing scale) and quantitative (joint space width measurement at 3 different points). All qualitative methods used standardized atlases. The intraclass correlation coefficient and the graphical method of Bland and Altman were used to assess cross sectional and longitudinal reproducibility. Reproducibility was tested using 2 readers (interreader) and 2 readings for one of the readers (intrareader). Sensitivity to change was assessed using standardized response mean (SRM). RESULTS: All methods tested were shown to be reproducible both for cross sectional and longitudinal data. Intrareader was higher than interreader reproducibility for most radiographic features. Significant changes were observed after one year for methods measuring joint space narrowing. The sensitivity to change of the methods assessing joint space narrowing (joint space narrowing scale and joint space width measurement) was higher, with SRM varying from 0.37 to 0.57, than for the Kellgren and Lawrence grading system (SRM 0.19 and 0.23). CONCLUSION: These data suggest that methods measuring narrowing should be preferred as outcome measures in clinical trials or longitudinal epidemiologic studies; and show that in a particular subset of patients with very active disease, significant radiographic changes in knee OA can be detected after a one year period.
Lysosomal enzymes and IGF-II both bind to the mannose 6-phosphate (M6P)/IGF-II receptor. This receptor targets newly synthesized lysosomal enzymes to lysosomes. The functional meaning of IGF-II binding to this receptor is not well known. We have postulated that IGF-II, the Ser29 IGF-II variant (vIGF-II) and IGF-I on lysosomal cathepsin B and L activities from post-natal rabbit chondrocytes in vitro. This effect was compared with the ability of each peptide to stimulate chondrocyte-sulfated proteoglycan synthesis. The sulfating dose-response relationship of the IGF peptides corresponded to their relative binding affinities for the type I-IGF receptor (IGF-I > IGF-II > vIGF-II). The intracellular cathepsin B and L activities were inhibited in a time- and dose-dependent manner by IGF-II or vIGF-II. Maximal inhibition of cathepsin B and L activities (40 and 30% below controls, respectively) was found after an 8 h treatment with 100 ng/ml IGF-II or vIGF-II. By contrast, IGF-I up to 1 micrograms/ml or insulin up to 2 micrograms/ml had no inhibitory effect. The relative potency pattern corresponded to the binding profile of each ligand for the M6P/IGF-II receptor. A treatment of chondrocytes with IGF-I or insulin transiently increased the binding of radiolabelled IGF-II at the cell surface to approximately 120% of controls, whereas IGF-II or vIGF-II had no effect. Thus, it is unlikely that the inhibition of lysosomal enzyme activities by IGF-II peptides could result from a redistribution of M6P/IGF-II receptors from intracellular compartments to the plasma membrane. We hypothesize that internalized IGF-II peptides could occupy the intracellular M6P/IGF-II binding sites required for targeting of cathepsins B and L to lysosomes.
STUDY OBJECTIVE: to investigate clinical, laboratory test, and bone mineral density abnormalities in 19 adults with phosphate diabetes of unknown etiology diagnosed in a rheumatology department on the basis of a maximal rate for tubular reabsorption of phosphate (TmPO4/GFR) of 0.77 or less. RESULTS: there were 14 males and five females with a mean age of 36.7 years (range 20 to 68 years) at symptom onset and 43.9 years (24-70) at diagnosis. Seventeen patients (90%) had back pain and 13 (68%) had nerve root pain. The pain was nocturnal only or both nocturnal and diurnal in 14 cases (74%). Other manifestations were fatigue (n = 7, 37%), myalgia (n = 6, 32%), fracture (n = 6, 32%), renal colic (n = 4, 21%), and pseudodepression (n = 10, 53%). Laboratory test abnormalities were as follows: serum phosphate, 0.72 mmol/L (0.58-0.89); rate for tubular reabsorption of phosphate, 74% (54-84%); maximal rate for tubular reabsorption of phosphate, 0.58 (0.4-0.76); urinary calcium/urinary creatinine > 0.48 in nine patients (47%); and fractional potassium excretion > 20% in seven patients (37%). Normal values were found for serum levels of Ca++, Na++, Mg++, creatinine, cortisol, T3, T4, TSH, 25(OH)D3, and 1,25(OH)2 D3. Tests for glycosuria and amino aciduria were negative. Bone mineral density measurements showed z-scores of -2.13 (+0.9 to -4.25) at L2-L4, and -1.34 (+1.5 to -3.2) at the femoral neck. Bone histology showed osteoporosis with a mild increase in osteoid deposition. CONCLUSIONS: idiopathic adult-onset phosphate diabetes manifests as chronic back pain and nerve root pain, sometimes with fatigue and depression. Bone mineral density values are decreased and histology shows osteopenia. Differential diagnoses include spondyloarthropathy, disk disease, fibromyalgia, and depression. Determination of the maximal rate for tubular reabsorption of phosphate is the only means of establishing the diagnosis.
Interleukin 1 beta was found to stimulate arachidonic acid release, and the synthesis and secretion of type II phospholipase A2 by rabbit articular chondrocytes in vitro. Interleukin 1 beta had no effect on the level of cytosolic phospholipase A2 mRNA. Insulin-like growth factors, which help stabilize the cartilage matrix, reduced the effect of interleukin 1 beta on type II phospholipase A2 activity and mRNA level, and decreased the Interleukin 1 beta-stimulated arachidonic acid release to the basal values. This suggests that type II phospholipase A2 plays a key role in arachidonic acid release from rabbit articular chondrocytes and that insulin-like growth factors counteract the effect of interleukin 1 beta. They may therefore be considered as potential antiinflammatory agents.
The purpose of this study was to evaluate the performance (simplicity, reproducibility, relevance) of chondroscopy as a method for evaluating cartilage damage. Chondroscopy consisted in endoscopic evaluation of the knee using a 2.7-mm Storz arthroscope under local anesthesia and recorded on videotape. Scoring of chondropathy was based on physician's overall assessment using a 100-mm-length visual analogue scale (VAS) and size and grade of cartilage lesions. Reproducibility was evaluated by variability (coefficient of variation [CV]) in the reading of chondroscopic evaluations of five patients five times by one physician and one time each by four different physicians. The correlations between scoring of chondropathy (VAS) and radiological articular joint space narrowing, demographic data (sex, age, weight), and disease characteristics (localization, etiology, activity) were studied in 84 outpatients fulfilling the American College of Rheumatology criteria for the diagnosis of osteoarthritis of the knee. The grade and size of the lesions were both correlated with the physician's overall assessment (r = 0.713 and r = 0.816, respectively). These two variables accounted for 72% of the variance of the VAS (multiple regression analysis). Intraobserver reproducibility was better than interobserver reproducibility (CV, 9% and 37%, respectively). There was a strong correlation between the scoring of chondropathy (VAS) and radiological joint space narrowing (r = .646, P < .0001). Moreover, in 17 of 33 patients without radiological joint space narrowing, VAS was > 20 mm. At variance, the body mass index was the single clinical variable found to correlate with the scoring of chondropathy (r = .282, P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVES: To evaluate the feasibility, relevance, and sensitivity of the French version of the revised Arthritis Impact Measurement Scale (AIMS2) in patients with rheumatoid arthritis or osteoarthritis of the hip. METHODS: translation of the English-language AIMS2 into French using the back-to-back technique; evaluation of feasibility on the basis of a) time needed to complete the AIMS2; b) percentage of questionnaires with at least one missing answer or one answer indicating that the question was misunderstood; evaluation of relevance on the basis of correlations between AIMS2 scores and conventional parameters for evaluating the activity of rheumatoid arthritis (85 patients); evaluation of sensitivity on the basis of total hip replacement-induced improvements in AIMS2 scores versus other conventional scores used to evaluate activity of osteoarthritis of the hip (48 patients). RESULTS: feasibility, mean time needed to complete the AIMS2 was 23 minutes in rheumatoid arthritis patients and 26 minutes in osteoarthritis patients. Forty per cent of patients failed to answer at least one question and 21% misunderstood at least one question; relevance: conventional parameters used in rheumatoid arthritis accounted for 51% of AIMS2 score variance, suggesting that the AIMS2 provided information not supplied by conventional parameters. SENSITIVITY: after total hip replacement for osteoarthritis, there were statistically significant decreases in all AIMS2 scores (with the exception of function and work). CONCLUSION: These data suggest that the AIMS2 score is not an easy evaluation tool but is both relevant and sensitive. These findings require confirmation by longitudinal studies.