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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Normal cartilage is a complex material consisting of a solid matrix composed primarily of collagen and proteoglycan, which is saturated with water. It is not a homogenous material. The interaction of the physical and biochemical structures of cartilage is necessary to allow the normal function of providing nearly frictionless motion, wear resistance, joint congruence, and transmission of load to subchondral bone. Chondrocytes are responsible for synthesizing and maintaining this material. Osteoarthritis occurs when there is disruption of normal cartilage structure and homeostasis. Osteoarthritis results from a complex interaction of biochemical and biomechanical factors that occur concurrently and serve to perpetuate degradative change. The progressive pathologic change that occurs in osteoarthritis has been characterized, not only for articular cartilage but also for periarticular tissues. The occurrence of mechanical and biochemical changes is well established, but the role of each in the etiopathogenesis of osteoarthritis is not rigidly defined. It is likely that there are multiple etiologies sharing common pathways of physical and chemical disruption. (see Fig. 1). The changes associated with osteoarthritis ultimately have an impact on the patient through decreased ability to use the joint or the production of pain, or both. Unfortunately, once these changes are severe enough to be recognized clinically, they are likely to be irreversible with current treatments. Nevertheless, understanding the basic mechanisms involved in the development and progression of osteoarthritis provides a basis for establishing a reasonable expectation for the patient and a rational plan for medical and surgical treatment of this condition.
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PMID:Osteoarthritis. Joint anatomy, physiology, and pathobiology. 924 77

CHONDROPROTECTIVE DRUGS: Long-acting chondroprotective drugs have a symptomatic effect. They are only effective in subjects with osteoarthritis and have no pure pain relieving effect. They act within several weeks, improve functional manifestations and have a remnant effect. CHONDROITIN SULFATES 4&6: CS 4&6 are glycosaminoglycans which participate in the matrix structure of cartilage. They are well absorbed after oral intake. They have a dose-dependent inhibitor effect in vitro on proteoglycan and collagen catabolism and have been shown to stimulate matrix synthesis. Several clinical studies have demonstrated the chondroprotective efficacy of CS 4&6 in osteoarthritis involving the hip, knee and finger joints. OSTEOARTHRITIS OF THE KNEE: A controlled randomized double-blind study versus placebo was conducted in 104 patients with femorotibial osteoarthritis. The objective was to demonstrate that CS 4&6 given orally in a sequential regimen at the dose of 800 mg/d has a beneficial effect both in terms of clinical manifestations and in terms of the anatomic progression in patients with osteoarthritis of the knee. The main efficacy criteria was the Lequesne functional score. After 1 year of treatment with CS 4&6, the functional impairment was reduced by approximately 50%, a significant improvement over placebo for all clinical criteria. Tolerance was excellent or good in more than 90% of the cases. A STRUCTURE MODULATOR: This study suggests that chondroitin sulfates act as structure modulators as shown by the improvement in the interarticular space visualized on the x-rays of patients treated with CS 4&6.
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PMID:[Anti-arthrosis treatments: efficacy and tolerance of chondroitin sulfates (CS 4&6)]. 985 36

NSAIDs are a major cause for concern for their propensity to cause joint deterioration in canine, as in human, patients receiving these drugs for treatment of pain in osteoarthritis and other acute and chronic painful conditions. To determine the potential effects of the new NSAID meloxicam on cartilage integrity, the effects of this drug on proteoglycan biosynthesis in vitro and ex vivo were compared with those of indomethacin, a known inhibitor of sulphated proteoglycans that accelerates joint injury in human osteoarthritis. In vitro cartilage proteoglycan synthesis from a radiosulphate precursor was unaffected by 0.5-10.0 micromol/L meloxicam but was significantly inhibited by 50 micromol/L indomethacin after 6 or 24 h incubation of femoral or tibial cartilage explants in organ culture. This is in accord with previous observations in human or porcine articular cartilage under the same culture conditions. Studies were performed in vivo to establish the effects of the NSAIDs on joint integrity. This involved determining cartilage proteoglycan synthesis ex vivo, leukocyte, fluid and protein accumulation, as well as pain relief. Thus, meloxicam (0.2 mg/kg i.v. x 3 doses) or indomethacin (0.5 mg/kg i.v. x 3 doses) was given for 26 h and the effects were compared with a control (1.0 ml saline i.v. x 3 doses) in dogs in which acute inflammation had been induced by intra-articular (i.a.) injection of calcium pyrophosphate dihydrate (CPPD) crystals into the right stifle joint, an equivalent volume of saline being injected into the left stifle joint as a control. No effects were observed of the treatment with the NSAIDs on ex vivo sulphated proteoglycan synthesis. The lack of the expected inhibitory effects of indomethacin may be related to the relatively low plasma concentrations of this drug obtained during the 26 h period of treatment. The pain response, which was elicited up to 6 h following i.a. injection of CPPD crystals, was totally prevented by the treatment with meloxicam and to a lesser extent with indomethacin. There were no effects from the drug treatment on synovial inflammatory reactions (fluid and cell accumulation), although the protein concentration of the exudate was reduced by meloxicam. This indicates that, at the doses given, it was possible to discriminate the analgesic action from the anti-inflammatory action of the two NSAIDs, this being achieved at relatively low plasma concentrations of these drugs. In conclusion, while relatively high therapeutic concentrations of indomethacin inhibit cartilage proteoglycan synthesis, this is not an effect seen even at high concentrations of meloxicam. Furthermore, the lack of effects on proteoglycan synthesis was evident when these two drugs were given in vivo to dogs. However, the signs of pain, but not the inflammation in the joint, were relieved by low plasma concentrations of the drugs. Meloxicam may thus be safely employed for acute analgesia without the potential risks of joint cartilage damage that occurs with indomethacin given at antiinflammatory doses for long periods of time.
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PMID:Effects of the NSAIDs meloxicam and indomethacin on cartilage proteoglycan synthesis and joint responses to calcium pyrophosphate crystals in dogs. 1035 54

Osteoarthritis of the knee is a leading cause of chronic disability in the United States. It is a heterogeneous condition that causes pathogenic changes that are presumably irreversible. In many cases, knee pain is often progressive and leads the patient to seek medical attention. Pharmacologic and nonmedicinal treatments are, in most cases, only modestly successful in relieving pain. Hyaluronic acid (HA) functions as the backbone of the proteoglycan aggregates necessary for the functional integrity of articular cartilage of the knee. Two drugs made up of HA derivatives have recently become available for patients in whom simple analgesics and conservative non-pharmacologic therapy have failed. This article reviews the epidemiology, pathogenesis, diagnosis, and medical management of osteoarthritis of the knee, with an emphasis on the physiologic and pharmacologic mechanisms of HA. Health care providers may administer HA via intra-articular injection in primary care, rheumatologic or orthopedic settings, or they may refer their patients to specialists for consultation.
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PMID:Hyaluronic acid treatment for osteoarthritis of the knee. 1041 69

A 68-year-old woman developed large subcutaneous masses on her abdomen and thighs after a bruise sustained in a traffic accident. She had severe pain when sitting up straight. Histological examination revealed calcified tissues in the entire dermis of the injured areas. On electron microscopy, crystalline materials were observed in the dermis, which seemed to be formed by the deposition of hydroxyapatite on unusual proteoglycan. In a vessel wall, a thick, layered basement membrane was observed. This suggests that vascular injury and subsequent hypoxia play a role in the process of calcinosis. We performed a partial resection with good results in alleviating the patient's pain.
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PMID:Tumoral calcinosis: a case report with an electron microscopic study. 1069

Patellar tendinosis is characterized by longstanding localized and activity-related pain, swelling and tenderness on palpation, and characteristic features on magnetic resonance imaging and ultrasonography and during surgical excision. Histologic examination of tendinosis tissues shows disrupted collagen matrix, increased cellularity, and increased proteoglycan stainability, but lack of inflammatory cell infiltration despite the clinical signs resembling inflammation. Disturbances in inflammatory response may be associated with the development of tendinosis. Expression of cyclooxygenase-2 and transforming growth factor-beta1 were detected in tendinosis, and the in vitro production of prostaglandin E2 by tendinosis and healthy tendon fibroblast cultures also was observed. Eleven patients with patellar tendinosis and 12 control subjects with healthy patellar tendons, but deficient anterior cruciate ligaments, were included in the current study. The percentages of immunopositive cells in tendinosis samples for cyclooxygenase-2 and transforming growth factor-beta1 were 66.75 and 56.40, respectively, which were significantly higher than those of the control subjects (25.15 and 23.06 respectively). Tendinosis fibroblast culture also produced more prostaglandin E2 and active transforming growth factor-beta1. These findings indicate the involvement of prostaglandins and cytokines that may explain the clinical symptoms and nonhealing features of tendinosis.
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PMID:Increased expression of transforming growth factor-beta1 in patellar tendinosis. 1207 60

Although the predominant mechanism of intra-articular hyaluronan (hyaluronic acid) (HA) and hylans for the treatment of pain associated with knee osteoarthritis (OA) is unknown, in vivo, in vitro, and clinical studies demonstrate various physiological effects of exogenous HA. HA can reduce nerve impulses and nerve sensitivity associated with the pain of OA. In experimental OA, this glycosaminoglycan has protective effects on cartilage, which may be mediated by its molecular and cellular effects observed in vitro. Exogenous HA enhances chondrocyte HA and proteoglycan synthesis, reduces the production and activity of proinflammatory mediators and matrix metalloproteinases, and alters the behavior of immune cells. Many of the physiological effects of exogenous HA may be a function of its molecular weight. Several physiological effects probably contribute to the mechanisms by which HA and hylans exert their clinical effects in knee OA.
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PMID:Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: mechanisms of action. 1271 45

This paper presents the preliminary investigation on chondromalacia patella at our department in recent years. A random cluster sampling survey covering 2743 normal persons was carried out. The prevalence rate is 36.2%. It was found that, applying transmission electron microscope and immunohistochemical methods on to cartilage tissues of the abnormal region, articular cartilage necrosis was in direct proportion with the abnormal pressure, while the restoration capability of local chondrocytes was in inverse proportion with pathological changes and the pressure. The chondromalacia patella was produced by repeated abnormal stress acting on the cartilage. The stress derived from the uncongruency and the decreasing in the contact area of patellofemoral joint when the subluxation or tilt of patellae was caused by the abnormal anatomical and biomechanical relationship. The initial lesion was at the matrix of cartilage, the collagen network was disrupted, then proteoglycan was lost. The microenvironment of chondrocytes was changed with degradation of matrix. So the chondrocytes became degenerative and necrosis from superficial to deep layer, then feed back the matrix again. Finally, the total cartilage layer might disappear, and the bone under cartilage might proliferate. At late stage, the cartilage was completely destroyed and had no self-restorative ability. Therefore, early diagnosis and treatment are necessary. It is highly suggested axis radiograph of the knee with the tibiae tuberositas localization are helpful to early diagnosis. Furthermore, JKY-Muscle Rehabilitation Instrument is invented for non-operative therapy. It enhances muscle power by selective training of the vastus medialis muscle using electrical stimulator to relieve pain and correct subluxation of patella with 90% efficiency (63% of excellent-effective rate). In late stage, patellofemoral replacement is recommended. The excellent-effective rate is 86.3%.
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PMID:[Preliminary investigation on the pathogeny, diagnosis and treatment of chondromalacia patella]. 1290 99

Osteoarthritis of the knee is common, increasing with age in both women and men, but is generally more prevalent in women following the fourth decade. Osteoarthritis may be primary/idiopathic or secondary as a consequence of trauma, surgery, infection, or another disease process. Normal articular cartilage is composed of an extracellular matrix and chondrocytes. This matrix contains water, collagen fibers, and proteoglycan macromolecules cross-linked into an integrated network with hyaluronic acid. Osteoarthritis represents an imbalance in the destructive and synthetic processes of the cartilage that leads to erosion of the cartilage. In addition, there is a decreased concentration and viscosity of the synovial fluid in osteoarthritic patients, and this may decrease the lubricating and cushioning properties of the joint. There is also an underlying inflammation of the synovium, as well as damage or reactive changes in the subchondral bone. The entire process is thought to involve a complex interaction of cells and soluble mediators such as cytokines, growth factors, inflammatory mediators, metalloproteinases, and chondrodegradative enzymes. Understanding the biochemical and molecular changes that occur in the joint is requisite to the development of treatments for osteoarthritis of the knee that address both the symptoms of pain and loss of mobility as well as the underlying disease progression. The clinical goal of the management of osteoarthritis should be to treat not only the symptoms of the disease, such as pain and decreased mobility, but also the underlying pathology of the degenerative process.
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PMID:Understanding osteoarthritis of the knee--causes and effects. 1500 94

Disc degeneration is considered a major source of pain in patients with chronic low back pain. Novel strategies to cure or decrease the symptoms and increase the patient's quality of life and function are under development. Until recently conservative treatment and fusion surgery were the main therapeutic options. Disc prostheses are undergoing clinical evaluation. The potential for cell transplantation to the intervertebral disc with mature autologous disc cells, chondrocytes, or stem cells is in early stages of investigation. Cell transplantation potentially can increase proteoglycan production and induce disc regeneration or slow down the degeneration process. In animal models, transplantation of autologous disc cells and chondrocytes (derived from costal cartilage) has been demonstrated to be feasible and may slow disc degeneration.
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PMID:Cell therapy for disc degeneration--potentials and pitfalls. 1506 21


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