Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0184567 (acute pain)
 3,962 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The elucidation of inducible cyclooxygenase (Cox-2) dependent inflammatory pathways led to the development of specific Cox-2 inhibitors, the coxibs. These agents include the currently available celecoxib and rofecoxib and such second-generation agents as parecoxib, valdecoxib, and etoricoxib. The therapeutic advantage of coxibs is founded primarily in their lack of significant gastrointestinal (GI) side effects. Clinical trials have demonstrated the efficacy of coxibs to be completely comparable with traditional nonsteroidal anti-inflammatory drugs (NSAIDs), and pharmacoeconomics suggest favorable cost/benefit ratios with these agents compared with traditional NSAIDs, related to their reduced GI complication profiles and lower indirect costs associated with disability. Although several clinical questions remain (eg, use with low-dose aspirin, risk of thrombosis, myocardial infarction, edema, and hypertension), the emergence and clinical utility of coxibs is likely to continue on the basis of their efficacy and relative GI safety advantage. Although newer, more specific Cox-2 inhibitors may alter the choice, it is likely that this class of anti-inflammatories will become (if they have not already) the drugs of first choice in the treatment of acute pain, chronic pain, and most rheumatic conditions in the 21st century. In addition to the treatment of rheumatic conditions, it is possible that coxibs will also be of clinical utility in protection against malignant transformation and Alzheimer disease.
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PMID:Cox-2 inhibitors: today and tomorrow. 1200 72

Slow, time-dependent, irreversible, highly selective inhibitors of COX-2 (coxibs) have been used for the treatment of osteoarthritis and rheumatoid arthritis, as well as other disease entities such as acute pain, fever, neoplastic changes, and Alzheimer's disease, the pathomechanism of which is dependent on the coexisting inflammatory process or overexpression of cyclo-oxygenase (COX) genes. The article presents current state of knowledge about the clinical efficacy of coxibs (celecoxib, rofecoxib) compared to non-selective COX inhibitors. The physiology and pathophysiology of both COX isoforms (COX-1, COX-2) are also discussed.
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PMID:[Coxibs: highly selective cyclooxygenase-2 inhibitors. Part I. Clinical efficacy]. 1286

The discovery of the two isoenzymes COX-1 and COX-2 and the knowledge of their function, localisation and regulation has initiated the development of COX-2 selective inhibitors (coxibs). Inducible COX-2 at the peripheral site of inflammation has been detected in the early 1990s, the involvement of recently detected spinal COX-2 has led to new insights into mechanisms of pain and may explain analgesic and antipyretic properties of COX-2 selective inhibitors. The coxibs rofecoxib and celecoxib have been introduced into therapy and seem to offer some advantages over the classical non-selective NSAIDs. The search for new COX-2 inhibitors is going on, the development of etoricoxib and lumiracoxib is a step ahead concerning efficacy, tolerability and safety. Until today COX-2 selective inhibitors have found their place in therapy of arthritis, osteoarthritis, dysmenorrhea and acute pain. A new paradigm in pain therapy seems to justify their use in perioperative settings in a preemptive or multimodal therapeutical strategy. In the future COX-2 selective inhibitors as opioid sparing agents could become an important tool in pain therapy. Even a therapeutical benefit of COX-2 selective inhibitors in the treatment of Alzheimer's Disease or in the prevention or treatment of colorectal or prostate cancer is presently intensely investigated. Recently some authors reported on COX-3, a splicing variant of COX-1. If COX-3 really represents the target for acetaminophen must be called into question.
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PMID:Novel insights and therapeutical applications in the field of inhibitors of COX-2. 1557 5

Several studies have suggested a lower consumption of analgesics in patients with Alzheimer's disease (AD) than in cognitively intact individuals (ND), but little attention has been paid to a distinction in analgesic consumption between acute and chronic pain treatment. The aim of this prospective and longitudinal study is a comparison in AD and ND residents at selection, and one year later, of analgesic consumption for acute and chronic pain, with an assessment of cognitive status (with the Mini Mental State Examination (MMSE)). Three hundred institution residents (150 AD and 150 ND), 20% male and 80% female (84.4 +/- 8.3 years old), were included in this study. Analgesic consumption and MMSE were reassessed at one year's distance (period 1 P1 and 2 (P2)). Analgesic consumption for acute pain was not significantly different for AD and ND at selection time or one year later, while MMSE declined significantly for AD (6 +/- 7 (P1) versus 4 +/- 6 (P2) p < 0.01, and ND individuals 23 +/- 5 (P1) versus 20 +/- 6 (P2), p < 0.01, respectively). Chronic pain analgesic consumption however was significantly lower in AD than in ND (p < 0.01). These findings may suggest a dissociation between sensory-discriminative (lateral pain system) and motivational-affective (medial pain system) aspects of pain in individuals with AD. This dissociation must be further investigated as it may have important consequences for pain evaluation and pain treatment in this vulnerable population.
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PMID:Acute versus chronic pain treatment in Alzheimer's disease. 1608 72

The introduction of celecoxib (Celebrex, Figure 1; GD Searle and Co) as the first cyclooxygenase (COX)2 selective inhibitor in the US and the expected introduction of rofecoxib (Vioxx; Merck and Co Inc) as the first COX2 inhibitor with an acute pain indication, has prompted interest in this class of drugs as a possible therapeutic improvement on dual COX1/COX2 inhibitor NSAIDs, currently on the market. Recognition that the COX-2 enzyme may have a broader role than pain and inflammation has led to studies investigating the efficacy of COX-2 inhibitors for Alzheimer's disease (AD), stroke, cardiovascular disease and colon cancer. Speakers at the second annual conference sponsored by IBC, addressed issues ranging from the basic concepts of COX2 specificity versus selectivity, pathways and regulatory factors related to COX2 expression, the principles underlying the possible broad implications of the COX2 mechanisms, as well as summaries of recently completed clinical trials supporting the clinical efficacy and safety of COX2 inhibitors in humans. The timeliness of this meeting is emphasized by the recent approval of rofecoxib by the FDA Arthritis Advisory panel and the initial reports in the media of toxicity attributed to celecoxib. Preclinical and limited clinical data presented suggest possible therapeutic roles for selective COX2 inhibitors in neurodegeneration due to both AD and stroke, the prevention and treatment of colon cancer, prevention of premature labor, as well as pain and inflammation.
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PMID:COX-2 inhibitors--IBC conference. 12-13 April 1999, Coronado, CA, USA. 1612 36

Cyclin-dependent kinase 5 (cdk5) is a member of the serine-threonine kinase family of cyclin-dependent kinases. This family is known for its role in the cell cycle, but cdk5 differs due to its interaction with activators p35 or p39, both abundant in post-mitotic neurons. Cdk5 is not known to have a role in cell cycle regulation at all, but is known to be an important modulator of neuronal activity. Cdk5 has been an attractive target for CNS diseases for a number of years. Among its attractions is the possibility that inhibitors will prevent the pathological phosphorylation of tau and neurofibrillary pathology in both Alzheimer's disease and tauopathies. More recently, there has been evidence that cdk5 is involved in the processing of pain and therefore inhibitors would also have potential therapeutic value for acute pain. Several classes of potent chemical inhibitors for cdk5 have been identified but most are competitive with the ATP binding site, resulting in a lack of specificity among the other cyclin-dependent kinases as well as other ATP-dependent kinases. We are working to discover specific inhibitors that might disrupt the interaction of tau and cdk5 at sites other than the ATP binding site. We are screening our compound library of 110,000 compounds using the full length tau as a substrate and will separate ATP competitive from non-competitive binders. In addition, we are taking a computational approach with virtual screening to identify non-ATP-competitive binders. These two approaches may lead to the discovery of site-specific inhibitors for tau and cdk5 interactions rather than competitive inhibitors for ATP binding. The hope is that non-ATP competitive compounds will more likely be selective and will be better therapeutics.
Curr Alzheimer Res 2007 Dec
PMID:New approaches to the discovery of cdk5 inhibitors. 1822 May 19

Timely and important studies are reviewed and commentaries provided by leading palliative care clinicians. Symptoms, interventions, and treatment-related adverse events addressed in this issue are management of Alzheimer's agitation with donepezil; needle-free lidocaine powder for minor painful procedures; psychostimulants in depression; anticoagulation for cancer-related venous thromboembolism; effect of waiting for acute pain treatment on risk of chronic pain; and an update on severe cutaneous reactions associated with medications.
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PMID:Pain and palliative care pharmacotherapy literature summaries and analyses. 1929 57

Cyclooxygenase (COX) enzyme is responsible for the formation of important biological mediators including prostaglandins, prostacyclin and thromboxane to trigger many physiological and patho-physiological responses. COXs exist in two distinct isoforms, a constitutively expressed form (COX-1) and an inducible form (COX-2). COX-2 is involved in the body's response to inflammation and pain. Moreover, it has also been shown that COX-2 is overexpressed in many human cancers, and that COX-2 is involved in various neurodegenerative diseases such as Parkinson's and Alzheimer's disease. COX-2 inhibitors are among the most widely used therapeutics for the treatment of chronic and acute pain and inflammation. Non-invasive monitoring of COX-2 functional expression by means of nuclear molecular imaging techniques like positron emission tomography (PET) and single photon emission computed tomography (SPECT) might provide unique opportunities to obtain data on COX-2 expression levels during disease manifestation and progression to study potential roles of COX-2 under various pathological conditions. The present review summarizes recent research efforts directed to the design and synthesis of radiotracers as molecular probes with special emphasis on COX-2 imaging.
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PMID:Radiotracers for molecular imaging of cyclooxygenase-2 (COX-2) enzyme. 2405 37

Placebo effects are well established in healthy participants experiencing experimental or acute pain. Yet, little is known about the mechanisms of placebo analgesia effects in patients with chronic pain and even less is known in patients suffering from central nervous system (CNS) diseases where pain is prevalent, difficult to manage, and often undertreated. This article briefly reviews the current knowledge of placebo analgesia effects in healthy participants with the aim of discussing how the mechanisms in placebo analgesia differ between healthy participants and patients. The focus will be on placebo analgesia effects in chronic pain conditions as well as in 2 CNS diseases: Alzheimer disease and Parkinson disease. Finally, strengths and weaknesses of the current knowledge will be discussed and it will be demonstrated how insights from the placebo literature may point to new ways of improving treatments among patients experiencing pain in relation to CNS diseases.
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PMID:Placebo analgesia effects across central nervous system diseases: what do we know and where do we need to go? 3158 43