Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteoarthritis, the most common form of arthritis, is a debilitating progressive disease principally affecting the elderly. Osteoarthritis therapy has evolved in the past few decades from symptomatic treatment to possible disease-modifying solutions. In this paper, the pathophysiology of osteoarthritis is first reviewed, including an examination of the mechanisms underlying osteoarthritis and discussions of the roles of cartilage, synovial fluid and subchondral bone. The remainder of the paper discusses therapeutic approaches in current use and those in development, with special attention given to pharmacological treatments. Current approaches to treating osteoarthritis--i.e. medications; nonpharmacological modalities, such as physical therapy, exercise, weight management and orthotics; and (as a last resort) surgery--focus on reducing pain and improving (or at least maintaining) mobility. Drugs currently used to treat osteoarthritis fall into several categories: analgesics, NSAIDs, cyclo-oxygenase-2 (COX-2) inhibitors, corticosteroids, viscosupplementation, and symptomatic slow-acting drugs ('nutraceuticals'). The analgesics (paracetamol [acetaminophen] and opiates) have demonstrated less symptomatic efficacy than NSAIDs, while the latter have displayed mixed results in terms of joint space narrowing. COX-2 inhibitors have been demonstrated to be equal to or superior to NSAIDs in effectiveness. However, once considered a safer alternative, COX-2 inhibitors have become the subject of intense scrutiny since recent clinical evidence has cast suspicion on their cardiovascular safety profile. Injectable therapies, such as corticosteroids and viscosupplementation have elicited favorable short-term response but no long-term structural modification. On the other hand, the slow-acting drugs, especially chondroitin and glucosamine sulfate, have shown promising results. Also reviewed are other established and experimental therapies that seek to modify and/or even reverse the course of osteoarthritis. These include such medications as colchicine, bisphosphonates and hormones; dietary therapeutics, such as ginger extract and green tea; and such truly experimental treatments as matrix metalloproteinase inhibitors, cytokines, nitric oxide, growth factors and gene therapy. Osteoarthritis continues to be a difficult disorder to treat, as there is no cure as such and current treatments focus mainly on relieving pain and maintaining joint function. The search nevertheless continues for management regimens that can slow, alter or reverse the degenerative processes of osteoarthritis.
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PMID:Disease-modifying therapies for osteoarthritis : current status. 1573 21

Osteoarthritis (OA) is currently defined by the American College of Rheumatology as a "heterogeneous group of conditions that leads to joint symptoms and signs which are associated with defective integrity of articular cartilage, in addition to related changes in the underlying bone at the joint margins." Its prevalence after the age of 65 years is about 60% in men and 70% in women. The etiology of OA is multifactorial, with inflammatory, metabolic, and mechanical causes. A number of environmental risk factors, such as obesity, occupation, and trauma, may initiate various pathological pathways. OA indicates the degeneration of articular cartilage together with changes in subchondral bone and mild intraarticular inflammation. The principal treatment objectives are to control pain adequately, improve function, and reduce disability. Acetaminophen is frequently used for symptomatic OA with mild to moderate pain. Nonsteroidal antiinflammatory drugs (NSAIDs) are more effective in the case of moderate-severe pain, but they have an increased risk of serious upper gastrointestinal adverse events. The newer cyclooxygenase COX-2 specific inhibitors (Coxibs) are as efficacious as traditional NSAIDs and have a better gastrointestinal safety profile. Other compounds (eg, chondroitin sulfate, diacerein, glucosamine sulfate) have a symptomatic effect that is slower and less than that of NSAIDs. The structure-modifying effects of drugs are currently being evaluated, and both glucosamine sulfate and diacerein have been shown in some trials to have a beneficial structural effect. Nonpharmacological interventions are frequently and widely used in the management of OA patients, but there is little evidence that they are effective: the best studied and most successful nonpharmacological interventions are patient education, self-management, and exercise. There is some evidence for the pain-relieving efficacy of thermotherapy and transcutaneous electrical nerve stimulation (TENS) but not of electrotherapy, acupuncture, homeopathy, or manual therapy. The value of interventions aimed at improving function and maximizing independence (occupational therapy, walking aids, workplace adaptation) is also unclear. The disease course and patient's requirements often change over time, thus requiring a periodic review and readjustment of therapy rather than the rigid continuation of a single treatment.
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PMID:Osteoarthritis: an overview of the disease and its treatment strategies. 1608 27

This review summarizes recent knowledge on the efficacy of glucosamine (GS) and/or chondroitin sulfate (CS) in the therapy of mild to moderate osteoarthritis (OA). OA, the most common joint disease is a significant source of disability, quality of life impairment and a considerable burden to any health care system. In the Czech Republic, glucosamine sulfate (GS) and chondroitin sulfate (CS) are available both as prescription drugs and as food supplements. Based on available data both are useful in the earlier stages of OA when combined with other modalities such as weight loss and exercises. They appear to relieve pain and improve range of the joint motion. In addition, they also display mild anti-inflammatory effects. However, controversy still exists over their ability to change significantly the natural history of the osteoarthritic joint. This effect is not easy to demonstrate for any other treatment modalities apart from joint replacement. Monitoring the cure efficacy by X-ray has been recently criticised and hence future techniques are anticipated for this reason. Further, long-term oral administration is required to obtain slightly increased levels of GS and/or CS in human blood. Both reviewed saccharides are well tolerated with negligible adverse reactions. In conclusion, the authors suggest that GS and CS should be classified as food supplements only.
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PMID:The efficacy of glucosamine and chondroitin sulfate in the treatment of osteoarthritis: are these saccharides drugs or nutraceuticals? 1617 Mar 88

We hypothesize that using a multi-variant nutrigenomic index for the purposes of customizing or adjusting the formulation of nutritional supplements will result in an improved and novel approach to the diagnosis, stratification, prognosis, and treatment of inflammatory processes in the human. This multi-variant genetic index, or Genoscore, is derived by analyzing genotype and/or phenotype through measuring multiple genetic mutations of single nucleotide polymorphisms, gene expression, or other forms of genetic and phenotypic measurements. We also propose that manipulation of neurochemical reward circuitry in the mesolimbic brain region providing dopamine release at the nucleus accumbens (NAc), will have both pain and stress relief benefists, which are a cornerstone to the human inflammatory process. This hypothesis, applies to all genes currently discovered or which will be discovered and any nutritional or dietary supplement ingredient currently available or which will become available. For example, if a DNA test was measuring two genes through single nucleotide polymorphisms (Gene A and Gene B), the index scores (Genoscore) that would be reported to the clinician and patient would be based upon the number of mutations. An index score of 0 would mean no mutation. An index score of 1 may mean a mutation in Gene A. An Index Score of 2 may mean a mutation in Gene B. An Index Score of 3 may mean a mutation in Gene A and Gene B, resulting in a simple report, easily understandable to both the clinician and patient that provides insights into disease diagnosis, stratification, prognosis, as well as the metabolism, efficacy and/or toxicity associated with specific vitamins, minerals, herbal supplements, homeopathic ingredients and other ingredients in the nutritional and/or dietary supplement regimen. Furthermore, we have provided support that evidence shows the importance of the dopaminergic connection as an anti-pain and anti-stress molecule, working at the mesocorticolimbic region of the brain, specifically at the NAc. Additionally, we have provided support that clinical evidence demonstrates the effectiveness and safety of natural substances for joint health, such as glucosamine sulfate , chondroitin sulfate, and Ganoderma lucidum.
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PMID:DNA based customized nutraceutical "gene therapy" utilizing a genoscore: a hypothesized paradigm shift of a novel approach to the diagnosis, stratification, prognosis and treatment of inflammatory processes in the human. 1640 2

With no disease-modifying osteoarthritis drugs on the immediate horizon, the goal of osteoarthritis therapy remains management of pain and maintenance of function. Evidence supports use of nonpharmacologic measures including patient education, judicious exercise and weight loss, and assistive devices when appropriate to reduce pain and further loss of function. First line pharmacotherapy is acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs). However, toxicities are associated with long-term use of these drugs. Evidence also supports the use of opioids in osteoarthritis pain management when other interventions are insufficient. NSAIDs and opioids are mutually dose sparing and combining relatively low doses of a drug from each class provides synergistic analgesia while limiting toxicity. Alternative therapies include tramadol and intra-articular injections of steroids and hyaluronic acid. There is evidence to support glucosamine as an adjunct in treating osteoarthritis. Evidence is lacking to support the use of chondroitin, S-adenosyl-methionine, or dimethyl sulfoxide in osteoarthritis pain management.
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PMID:Managing osteoarthritis pain when your patient fails simple analgesics and NSAIDs and is not a candidate for surgery. 1651 61

Over the last 10 years, several studies have investigated the ability of glucosamine sulfate to improve the symptoms (pain and function) and to delay the structural progression of osteoarthritis. There is now a large, convergent body of evidence that glucosamine sulfate, given at a daily oral dose of 1,500 mg, is able to significantly reduce the symptoms of osteoarthritis in the lower limbs and spine. This effect is usually seen with a minimal time for the onset of significant action - around 2 weeks. A similar dose of glucosamine sulfate has also been shown, in two independent studies, to prevent the joint space narrowing observed at the femorotibial compartment in patients with mild to moderate knee osteoarthritis. This effect, which is not affected by the radiographic technique used for the assessment of joint space width, also translated into a 50% reduction in the incidence of osteoarthritis-related surgery of the lower limbs during a 5-year period following the withdrawal of the treatment. There is a high degree of consistency in the literature showing that when glucosamine sulfate is used for the treatment of osteoarthritis, an efficacious response with minimum side effects can be expected. Since some discrepancies have been described between the results of studies performed with a patent-protected formulation of glucosamine sulfate distributed as a drug and those having used glucosamine preparations purchased from global suppliers, packaged, and sold over-the-counter as nutritional supplements (not regulated as drugs and with some potential issues concerning the reliability of their content), caution should be used when extrapolating conclusive results obtained with prescription drugs to over-the-counter or food supplements.
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PMID:Current concepts in the therapeutic management of osteoarthritis with glucosamine. 1653 16

Thirty-five dogs were included in a randomised, double-blind, positive controlled, multi-centre trial to assess the efficacy of an orally-administered glucosamine hydrochloride and chondroitin sulfate (Glu/CS) combination for the treatment of confirmed osteoarthritis of hips or elbows. Carprofen was used as a positive control. Dogs were re-examined on days 14, 42 and 70 after initiation of treatment. Medication was then withdrawn and dogs were re-assessed on day 98. Response to treatment was based on subjective evaluation by participating veterinarians who recorded their findings at each visit. Dogs treated with Glu/CS showed statistically significant improvements in scores for pain, weight-bearing and severity of the condition by day 70 (P<0.001). Onset of significant response was slower for Glu/CS than for carprofen-treated dogs. The results show that Glu/CS has a positive clinical effect in dogs with osteoarthritis.
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PMID:Randomised double-blind, positive-controlled trial to assess the efficacy of glucosamine/chondroitin sulfate for the treatment of dogs with osteoarthritis. 1664 70

Earlier studies with glucosamines in patients with osteoarthritis have shown conflicting results. A placebo-controlled randomised trial was now carried out in 1583 patients with osteoarthritis. The primary endpoint was a 20% reduction in knee pain between baseline and week 24 according to the 'Western Ontario and McMaster Universities arthritis index'(WOMAC)-score. No statistically significant difference was found between the groups using placebo (60% response), glucosamine (64%), chondroitin sulphate (65%) or combination therapy (67%). The results of this trial do not support the hypothesis that glucosamines have a positive effect on symptoms in patients with osteoarthritis of the knee. However, (a) the chance of a statistically significant difference decreases with increasing magnitude of the placebo response, (b) there was a statistically significant reduction in the patients with moderate to severe pain, (c) when the pain was assessed with the more sensitive 'Outcome measures in rheumatology clinical trials'(OMERACT)-'Osteoarthritis Research Society International'(OARSI)-score, there was a better response in the group given combined treatment, (d) the data on radiological progression and the effects on cartilage markers must still come in, and (e) the efficacy may have been higher ifa different dietary supplement had been used. These questions on the design and the robustness of the study indicate that further studies are necessary.
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PMID:[Effectiveness of dietary supplements in patients with osteoarthritis: the doubt persists]. 1695 38

This was a pilot study to test the potential effectiveness of intradiscal restorative injection therapy and compare with intradiscal electrothermal therapy (IDET). Thirty-five patients for intradiscal injection and seventy-four for IDET took part in the study. All patients had intractable chronic discogenic low back pain, confirmed by discogram study. Injection solution consisted of glucosamine and chondroitin sulfate combined with hypertonic dextrose and dimethylsulfoxide. Outcome was rated as 0-10 on visual analog scale (VAS), satisfaction rate, and flare up before and after the procedures. Post-procedure, patients were followed from 6 months to 18 months. Pain relief was statistically significant for both procedures, but slightly better for injections (2.2 VAS) than for IDET (1.27 VAS). 47.8% of IDET patients reported that they felt better, whereas 65.6% of injection patients reported this outcome. Among IDET patients, 35.8% reported they were worse, while no restorative injection patient reported worsening of pain. Post-procedure flare-up occurred more frequently after restorative injection (81%) than after IDET (68.9%) and was more severe (7.9 versus 6.1 VAS, respectively). However, the duration of pain flare-up was notably shorter for restorative injections (8.6 days) than for IDET (33.1 days). Biochemical intradiscal restorative injections may be useful to reduce pain and disability in patients with chronic discogenic low back pain, and have clinically similar efficacy to IDET, but with improved cost-benefit ratio. The results of this study indicate that controlled random prospective comparative studies need to be performed to establish the efficacy of this treatment.
Pain Physician 2004 Jan
PMID:Comparison of intradiscal restorative injections and intradiscal electrothermal treatment (IDET) in the treatment of low back pain. 1686 13

The purpose of this study was to examine whether glucosamine has an antirheumatic effect in a randomized placebo-controlled study. The subjects were 51 rheumatoid arthritis (RA) patients: 25 patients in the glucosamine group and 26 patients in the placebo group. Glucosamine hydrochloride at a daily dose of 1,500 mg and placebo, respectively, were administered for 12 weeks along with conventional medication. While significant improvement was not found in joint counts and in the rate of ACR20 responders, the face scale and a visual analogue scale pain were significantly in favor of the glucosamine group. ESR and CRP levels did not change, but serum MMP-3 levels decreased in the glucosamine group. Results of the patients' self-evaluations and the physicians' global evaluations indicated that the glucosamine treatment produced noticeable improvements in symptoms. Although glucosamine administration had no antirheumatic effect evaluated by conventional measures, it seemed to have some symptomatic effects on RA.
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PMID:Effects of glucosamine administration on patients with rheumatoid arthritis. 1695 94


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