Objective. An association between depression and inflammation has been suggested. In patients with rheumatoid arthritis (RA), pain is a major symptom associated with depression and inflammation. We examined the independent associations between depression, the inflammation marker C-reactive protein (CRP) level, and pain in patients with RA. Methods. In total, 218 RA outpatients completed self-administered questionnaires, using the Beck Depression Inventory II to measure depressive symptoms and a visual analog scale to quantify their perceived pain. Functional disability and CRP level were also measured. Results. Depression scores were mildly and positively correlated with the CRP level (r ‫؍‬ 0.46, P < 0.001). Both the depression score (standardized ␤ ‫؍‬ 0.35, P < 0.001) and the CRP level (standardized ␤ ‫؍‬ 0.35, P < 0.001) were significantly associated with pain, even after adjustment for clinical covariates in regression analysis. In logistic analysis, the combined effects on the risk of severe pain (pain score in the upper tertile) increased with depression scores and CRP levels linearly. Conclusion. Depression severity and inflammation were associated with each other and appeared to have independent effects on perceived pain. Therefore, a clinical approach that takes into account both the body and the mind could have benefits and could enable optimal pain control. INTRODUCTIONRheumatoid arthritis (RA) is a chronic autoimmune disorder causing inflammation of the joints and surrounding tissues (1). Patients with RA experience pain, stiffness, swelling, and deterioration of joints. Severe chronic pain accompanied by progressive joint destruction, disability, and disfigurement is known to increase the risk of experiencing emotional disturbances (2). Indeed, depression is common among patients with RA (3,4); these patients are twice as likely to be depressed as people in the general population (5).The association between systemic inflammation and depression has recently attracted attention (6 -8). Depression could promote inflammation by fostering poor health practices, dysregulation of hormonal systems, and susceptibility to atherogenic infections (9,10). Alternatively, it has been suggested that systemic inflammation might induce depressive symptoms by activating the immune-brain pathway (11,12). Various inflammation markers have been reported to have positive associations with depression. C-reactive protein (CRP) is a nonspecific acute-phase protein synthesized in the liver in response to stimulation from interleukin-6 (IL-6) and IL-1. According to a recent review (8), CRP and its precursors IL-6 and IL-1 are the most intensively examined inflammation markers in relation to depression, and a positive association has been confirmed consistently in community and clinical samples. Associations between depression and leukocytosis, increased CD4:CD8 ratios, reduced proliferative response to mitogen, and reduced natural killer cell cytotoxity were also suggested in an earlier meta-analysis (13,14).To date, the asso...

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Objective To determine interrelationships in matrix turnover in articular cartilage and joint inflammation in rheumatoid arthritis (RA). Methods Synovial fluid was obtained from the knees of 63 RA patients; radiographs were evaluated to determine the RA stage. Concentrations of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), the 846 epitope, and the keratan sulfate (KS) epitope of aggrecan, the C‐propeptide of cartilage type II procollagen (CPII; biosynthetic marker), the cleavage of type II collagen by collagenase (CIIC; generated neoepitope), and polymorphonuclear leukocyte elastase (PMNE; inflammation marker) were measured by immunoassay. Concentrations of the unsaturated disaccharides of hyaluronic acid (Δdi‐HA) and the proteoglycan glycosaminoglycan disaccharides of chondroitins 4 and 6 sulfate (Δdi‐C4S and Δdi‐C6S) were determined by high‐performance liquid chromatography. Results MMP‐3 was markedly increased in RA compared with osteoarthritis. Increases in TIMP‐1 in RA were less pronounced and were inversely correlated with MMP‐3 levels. CIIC was reduced in RA, as was the release of the KS epitope and Δdi‐C6S. In contrast, Δdi‐C4S and the 846 epitope were up‐regulated. PMNE levels correlated with the 846 epitope and Δdi‐C4S, and more strongly with TIMPs 1 and 2. The changes may signify attempts at control of proteolysis in parallel with increased aggrecan turnover, which would favor matrix assembly. PMNE also correlated with MMP‐9, and MMP‐9 correlated with CPII. The Δdi‐HA level was decreased in RA and was inversely correlated with CPII and MMP‐9 as well as with MMPs 2 and 3. In contrast, Δdi‐HA was directly correlated with TIMP‐1 and the 846 epitope. These observations suggest that HA and PMNs may be involved in the control of proteolysis and cartilage proteoglycan assembly. Conclusion Our observations provide new insights into the complex changes in cartilage turnover and PMN influx in RA joints.

This study compares the regulation of three isoforms of hyaluronan synthase (HAS1, HAS2, and HAS3) transcripts and hyaluronan (HA) production by cytokines in human synovial fibroblastic cells derived from tissue from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Levels of HAS mRNA of the cells with or without stimulation were detected using a real-time fluorescence polymerase chain reaction detection system. Concentrations of HA in the culture supernatants of the cells were measured by a sandwich binding protein assay. Molecular weight of HA was evaluated by agarose gel electrophoresis. The relative proportions of the expression pattern of HAS isoforms was similar between RA and OA tissue-derived cells. HAS1 mRNA was upregulated by transforming growth factor-beta and HAS3 mRNA was upregulated by interleukin-1beta and somewhat by tumor necrosis factor-alpha in the RA cells. HAS2 remained unchanged. Differences in the expression pattern of HAS1, HAS2, and HAS3 mRNA by cytokines suggest that these three isoforms are independently and differentially regulated, and each isoform of HAS may have a different role in arthritic joint disease.

The sedative effects of epidural anesthesia without volatile and IV anesthetics and quantification of the degree of epidural anesthesia-induced sedation have not been investigated. In the current study we evaluated the effects of epidural anesthesia on the bispectral index (BIS) during the awake phase and during general anesthesia. After placing the epidural catheter, the patients were randomly allocated to 2 groups receiving either 5 mL of epidural saline (group S) or the same volume of 0.75% ropivacaine (group R). The BIS measurements during the awake phase were performed at 7, 12, 13, 14, 22, and 23 min after the epidural injection. General anesthesia was then induced with propofol and vecuronium and maintained with 0.75% sevoflurane. From approximately 10 min after tracheal intubation, the BIS measurements were made at 1-min intervals for 10 min. The BIS during the awake phase was significantly lower in group R than in group S (P < 0.05). The BIS during general anesthesia was significantly lower in group R than in group S (P < 0.0001). Epidural anesthesia decreased the BIS during the awake phase and during general anesthesia. The decrease of the BIS associated with epidural anesthesia was more prominent during general anesthesia than during the awake phase.