DREAM is reduced in synovial fibroblasts of patients with chronic arthritic pain: is it a suitable target for peripheral pain management?

INTRODUCTION: The endogenous pain-relieving system depends in part on the regulation of nociceptive signals through binding of opioids to the corresponding opioid receptor. Interfering with the trans-repression effect of downstream regulatory element antagonist modulator (DREAM) on the transcription of the opioid dynorphin-encoding prodynorphin (pdyn) gene might enhance pain relief in the periphery. METHODS: Expression levels were measured in osteoarthritis (OA) synovial fibroblast-like cells (SFLCs) (n = 8) and in peripheral blood mononuclear cells (PBMCs) from OA patients (n = 53) and healthy controls (n = 26) by real-time polymerase chain reaction. Lysed OA SFLCs were analyzed by immunoprecipitation. Translation of DREAM mRNA was inhibited by small interfering RNAs (siRNAs). Expressions of DREAM, pdyn, and c-fos mRNAs were measured at 24, 48, and 72 hours after transfection. RESULTS: The expression of DREAM mRNA was shown in both healthy and OA SFLCs as well as PBMCs. Inhibiting transcription using siRNAs led to a marked reduction in DREAM expression after 24, 48, and 72 hours. However, no significant changes in c-fos and pdyn expression occurred. In addition, DREAM mRNA expression was significantly reduced in OA patients with chronic pain (pain intensity as measured by a visual analog scale scale of greater than 40), but no pdyn expression was detectable. CONCLUSION: To our knowledge, this is the first report showing the expression of DREAM in SFLCs and PBMCs on the mRNA level. However, DREAM protein was not detectable. Since repression of pdyn transcription persists after inhibiting DREAM translation, DREAM appears to play no functional role in the kappa opioid receptor system in OA SFLCs. Therefore, our data suggest that DREAM appears not to qualify as a target in peripheral pain management

Molecular profile of synovial fibroblasts in rheumatoid arthritis depends on the stage of proliferation

The aim of this study was to explore the molecular profile of proliferating rheumatoid arthritis synovial fibroblasts (RA-SF). Total RNA was extracted from two cultures of RA-SF (low-density [LD] proliferating cells and high-density [HD] nonproliferating cells) and suppression subtractive hybridization was performed to compare differential gene expression of these two cultures. Subtracted cDNA was subcloned, and nucleotide sequences were analyzed to identify each clone. Differential expression of distinct clones was confirmed by semiquantitative RT-PCR. The expression of certain genes in synovial tissues was examined by in situ hybridization. In both LD and HD cells, 44 clones were upregulated. Of the 88 total clones, 46 were identical to sequences that have previously been characterized. Twenty-nine clones were identical to cDNAs that have been identified, but with unknown functions so far, and 13 clones did not show any significant homology to sequences in GenBank (NCBI). Differential expression of distinct clones was confirmed by RT-PCR. In situ hybridization showed that certain genes, such as S100A4, NFAT5, unr and Fbx3, were also expressed predominantly in synovial tissues from patients with RA but not from normal individuals. The expression of distinct genes in proliferating RA-SF could also be found in RA synovium, suggesting that these molecules are involved in synovial activation in RA. Most importantly, the data indicate that the expression of certain genes in RA-SF depends on the stage of proliferation; therefore, the stage needs to be considered in any analysis of differential gene expression in SF

Prediction of grip and key pinch strength in 978 healthy subjects

<p>Abstract</p> <p>Background</p> <p>Hand strength is an important independent surrogate parameter to assess outcome and risk of morbidity and mortality. This study aimed to determine the predictive power of cofactors and to predict population-based normative grip and pinch strength.</p> <p>Methods</p> <p>A representative population survey was used as the basis for prediction analyses (n = 978). Bivariate relationships between grip/pinch strengths of the dominate hand were explored by means of all relevant mathematical functions to maximize prediction. The resulting best functions were combined into a multivariate regression.</p> <p>Results</p> <p>Polynoms (up to the third degree) were the best predictive functions. On the bivariate level, height was best correlated to grip (46.2% explained variance) and pinch strength (37.7% explained variance) in a linear relationship, followed by sex, age, weight, and occupational demand on the hand. Multivariate regression provided predicted values close to the empirical ones explaining 76.6% of the variance for grip strength and 67.7% for pinch strength.</p> <p>Conclusion</p> <p>The five easy-to-measure cofactors sex, age, body height, categorized occupational demand on the hand, and body weight provide a highly accurate prediction of normative grip and pinch strength.</p

Finite element analysis of the bone resorption in the humerus after shoulder arthroplasty

Presentatio

Treatment strategies for periprosthetic infections after primary elbow arthroplasty

BACKGROUND: The goal of this study was to investigate the outcome of different surgical procedures (debridement and retention vs 1- or 2-stage exchange) together with a well-defined antimicrobial regimen. MATERIALS AND METHODS: A total of 236 consecutive patients underwent 262 primary elbow arthroplasties between January 1994 and December 2007. We observed 20 episodes of periprosthetic infections in 19 patients and placed them into 3 groups according to the occurrence of infection after index surgery. A total of 9 early infections (24 months) were observed. The treatment among those 3 groups was compared, and the outcome was assessed with a mean follow-up of 60.2 months. RESULTS: In the group with early infections (n = 9), 8 cases were treated by irrigation and debridement and 1 case was treated by a 2-stage exchange without recurrence of infection. The mean Mayo Elbow Performance Score improved from 48.3 points (range, 30-75 points) to 91.7 points (range, 85-100 points). The delayed infection was treated by 1-stage exchange without recurrence of infection. For late infections (n = 10), 3 cases presented recurrence of infection after debridement and irrigation, and the mean Mayo Elbow Performance Score remained nearly unchanged, from 60 points (range, 45-80 points) to 65 points (range, 50-80 points). Eradication of infection could be achieved by staged revision and in 3 cases by debridement. CONCLUSION: Both debridement with retention and staged reimplantation are highly successful for appropriate indications. Staged revisions are successful even against biofilm-active microorganisms, but a prosthesis-free interval of at least 3 months is recommended

Extended overview of the longitudinal pain-depression association: A comparison of six cohorts treated for specific chronic pain conditions

BACKGROUND The aim was to quantify and to compare the associations between longitudinal changes in pain and depression in different chronic pain conditions. METHODS Data were retrieved from 6 observational cohort studies. From baseline to the 6-month follow-up, the score changes on the Short Form (36) Health Survey (SF-36) bodily pain (pain) and the SF-36 mental health (depression) scales (0=worst, 100=best) were quantified, using partial correlations obtained by multiple regression. Adjustment was performed by age, living alone/with partner, education level, number of comorbidities, baseline pain and baseline depression. RESULTS Stronger associations were found between changes in levels of pain and depression for neck pain after whiplash (n = 103, mean baseline pain=21.4, mean baseline depression=52.5, adjusted correlation r = 0.515), knee osteoarthritis (n = 177, 25.4, 64.2, r = 0.502), low back pain (n = 134, 19.0, 49.4, r = 0.495), and fibromyalgia (n = 125, 16.8, 43.2, r = 0.467) than for lower limb lipedema (n = 68, 40.2, 62.6, r = 0.452) and shoulder arthroplasty (n = 153, 35.0, 76.4, r = 0.292). Those correlations were somewhat correlated to baseline pain (rank r=-0.429) and baseline depression (rank r=-0.314). LIMITATIONS The construct of the full range of depressive symptoms is not explicitly covered by the SF-36. CONCLUSIONS Moderate associations between changes in pain and depression levels were demonstrated across 5 of 6 different chronic pain conditions. The worse the pain and depression scores at baseline, the stronger those associations tended to be. Both findings indicate a certain dose-response relationship - an important characteristic of causal interference. Relieving pain by treatment may lead to the relief of depression and vice versa

Relative DREAM gene expression in peripheral blood mononuclear cells from osteoarthritis (OA) patients and healthy controls

Relative gene expression was normalized to GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and is given as delta CT (dCT) value, with higher values representing lower expression levels. DREAM gene expression was significantly lower in OA patients with a high pain score (visual analog scale [VAS] score of greater than 40; △) compared with healthy controls (○) and with OA patients with a low pain score (VAS score of less than or equal to 40; ∇). No significant differences were observed between healthy controls and OA patients with a VAS score of less than or equal to 40. Statistics: one-way analysis of variance followed by Tukey's honest significant difference (*< 0.05). Ctrl, control; DREAM, downstream regulatory element antagonist modulator.<p><b>Copyright information:</b></p><p>Taken from "DREAM is reduced in synovial fibroblasts of patients with chronic arthritic pain: is it a suitable target for peripheral pain management?"</p><p>http://arthritis-research.com/content/10/3/R60</p><p>Arthritis Research & Therapy 2008;10(3):R60-R60.</p><p>Published online 28 May 2008</p><p>PMCID:PMC2483451.</p><p></p