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)

Control of malignant pain and related symptoms is paramount to clinical success in caring for cancer patients. To achieve the best quality of life for patients and families, oncologists and palliative care clinicians must work together to understand problems related to psychologic, social, and spiritual pain. Pain is the primary problem targeted for control using the World Health Organization's (WHO) analgesic ladder. This article focuses on increased knowledge of analgesic action that may enable expansion of the WHO analgesic ladder to fulfill the broader objectives of palliative medicine. We discuss clinical experience with several classes of drugs that are currently used to treat cancer pain: 1) nonsteroidal anti-inflammatory drugs (NSAIDs), with emphasis on cyclooxygenase-2 (COX-2) inhibitors; 2) opioid analgesics, with specific emphasis on methadone and its newly recognized value in cancer pain; 3) ketamine, an antagonist at N-methyl d-aspartate (NMDA) receptors; and 4) bisphosphonates, used for pain resulting from bone metastases. New concepts that compare molecular actions of morphine at excitatory opioid receptors, and methadone at non-opioid receptor systems, are presented to underscore the importance of balancing central nervous system excitatory (anti-analgesic) versus inhibitory (analgesic) influences.
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PMID:Advances in cancer pain management. 1112 64

Intraspinal injection of quisqualic acid (QUIS) produces excitotoxic injury with pathophysiological characteristics similar to those associated with ischemic and traumatic spinal cord injury (SCI). Responses to QUIS-induced injury include an inflammatory component, as well as the development of spontaneous and evoked pain behaviors. We hypothesized that QUIS-induced inflammation and subsequent gene expression contribute to the development and progression of pain-related behaviors and that blockade of inflammation-related gene expression leads to the amelioration of these behaviors. Using the QUIS model of spinal cord injury, we examined whether interleukin-10 (IL-10), a potent anti-inflammatory cytokine, is able to reduce mRNA levels of inflammatory and cell death-related genes leading to a reduction of pain behaviors. The results demonstrate that animals receiving systemic injection of IL-10, 30 minutes following QUIS-induced SCI, showed a significant delay in the onset of excessive grooming behavior, a significant reduction in grooming severity, and a significant reduction in the longitudinal extent of a pattern of neuronal loss within the spinal cord characterized as "grooming-type damage." QUIS injections also resulted in an increase in mRNA levels of interleukin-1 beta (IL-1 beta), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), CD95 ligand (CD95-L, also called FAS-L/APO-1L), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Results of QUIS injury plus IL-10 treatment resulted in a significant downregulation of IL1-beta and iNOS mRNA and these results were supported by Western blot analysis of protein levels following IL-10 treatment. These data suggest that IL-10 reduces inflammation and that targeting injury-induced inflammation is an effective strategy for limiting the extent of neuronal damage following excitotoxic SCI and thus the onset and progression of injury-induced pain behaviors.
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PMID:Effects of interleukin-10 (IL-10) on pain behavior and gene expression following excitotoxic spinal cord injury in the rat. 1117 Jul 29

Low back pain is a common problem, affecting approximately two-thirds of the adult population. Of these individuals, a significant percentage will exhibit symptoms of radicular pain or sciatica. The purpose of this study was to determine the effect of one systemic (2 mg/kg) or intrathecal (0.2 mg/kg) dose of a selective cyclooxygenase-2 inhibitor (SC-236) in decreasing existing mechanical allodynia in a rat model of radiculopathy. Gait disturbance and mechanical allodynia (increased response to non-noxious von Frey monofilament stimuli) were assessed daily until the rats were killed 7 days after surgery. Robust mechanical allodynia developed in the rats in all groups except for those in the sham group by day 1 after surgery. Mechanical allodynia was significantly lower in the rats that received the systemic or the intrathecal dose of SC-236 than in those in the vehicle control group (analysis of variance followed by Bonferroni multiple comparison test, p = 0.002). The intrathecal drug route of administration produced greater attenuation in allodynia than the systemic dose, supporting a central mechanism of action of the cyclooxygenase-2 inhibitor (p = 0.002). The hypothesis that cyclooxygenase-2 is involved in spinal nociceptive processing after a nerve root injury was supported by this study. In addition, these data support continued basic science research to further elucidate central inflammatory processes that follow nerve root injury.
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PMID:Cyclooxygenase-2 inhibitor SC-236 attenuates mechanical allodynia following nerve root injury in rats. 1119 59

Nimesulide (Aulin) refers to the class of sulphonanilides, which is unique among the non-steroidal antiinflammatory drugs (NSAIDs), being also the first drug on the market of pharmaceuticals, which preferentially inhibits the enzyme cyclooxygenase-2 (COX-2). This enzyme takes part in the synthesis of prostaglandin, which is produced in the course of the cascade of the inflammation process and has relation to the pathogenesis of pain, inflammation and fever, while the COX-1 enzyme forms prostaglandin, which projects the gastro-intestinal mucosis. Many newly found factors, together with the preferential inhibition of COX-2, are also contributing to the therapeutic effects of Nimesulide. The therapeutic concentration of non-combined active substance in blood-circulation reduces the following indicators: the activity of the myeloperoxidase; the release of cytokines; the histamine effects; the synthesis of stromelysin and collagenase, which pull down the proteoglicans and collagen. It is also characteristic of Nimesulide its antioxidant activity and suppression of: the synthesis of superoxidic ions from the neutrophils; also, the synthesis of platelet activating factor. Nimesulide shows good tolerability and is safe with patients having respiratory problems due to treatment with other NSAIDs.
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PMID:[Nimesulide - a non-steroidal anti-inflammatory drug, a preferential cyclooxygenase-2 inhibitor]. 1119 95

Gastric and duodenal injury related to nonsteroidal anti-inflammatory drug (NSAID) use is extremely common, and a variety of strategies can be employed to reduce this frequent side effect of an otherwise useful category of medications. Although the best approach may be to discontinue NSAID treatment, this is not always possible for patients with arthritis pain or for those who require low-dose aspirin therapy for underlying cardiovascular disease. In arthritis cases, one of the new cyclooxygenase-2 specific inhibitors can be used to replace a traditional NSAID, but the addition of another drug to treat and heal ulcers is normally still needed. Patients taking aspirin are also candidates for additional treatment.
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PMID:The impact of nonsteroidal anti-inflammatory drug-induced gastropathy. 1122 47

Rofecoxib (Vioxx, Merck & Co., Inc.) is a new orally-effective non-steroidal anti-inflammatory drug (NSAID) approved for treatment of acute pain, fever, primary dysmenorrhea and pain and inflammation in osteoarthritis (OA). It is also being evaluated for treatment of rheumatoid arthritis and adenomatous polyps of the colon. Rofecoxib is a specific inhibitor of cyclooxygenase-2 (COX-2), thereby inhibiting prostanoid synthesis in cells that express COX-2, including inflammatory cells. As cells in the gastrointestinal (GI) tract principally express COX-1, a different isoform of cyclooxygenase, it is predicted that rofecoxib will have less GI toxicity than other less selective NSAIDs. In clinical trials, rofecoxib was found to be as effective as other NSAIDs for management of pain and inflammation. In trials that compare rofecoxib with ibuprofen, diclofenac and indomethacin, less GI toxicity has been observed, as assayed by a decrease in lesions visible on endoscopy, by GI blood loss and, in a meta-analysis, by frequency of serious adverse GI events. The presence of COX-2 in cells other than inflammatory cells results in side effects common among NSAIDs, including peripheral oedema and hypertension. These side effects are dose-dependent. Rofecoxib, together with other branded NSAIDs, are relatively expensive, which has led to concern regarding costs versus benefits. There is also concern regarding potential risks associated with the use of rofecoxib by populations that would otherwise not tolerate NSAIDs.
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PMID:Rofecoxib. 1124 95

Nonsteroidal anti-inflammatory drugs (NSAIDs), which are used widely to manage pain, are known to inhibit cyclooxygenase, but details of the mechanisms of NSAID action remain unclear. We investigated the ability of three NSAIDs (indomethacin, loxoprofen, and etodolac) to eliminate and inhibit free radicals. Superoxide scavenging activity of these NSAIDs was measured in vitro by electron spin resonance spectrometry using 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) as a spin trap. Electron spin resonance demonstrated that formation of superoxide-DMPO spin adduct was completely inhibited by two nonselective cyclooxygenase inhibitors, indomethacin (3 mmol) and loxoprofen (3 mmol). The electron spin resonance study also demonstrated that the formation of superoxide-DMPO spin adduct was strongly inhibited by a selective cyclooxygenase-2 inhibitor, etodolac, in a concentration-dependent manner. These results indicate that NSAIDs, including indomethacin, loxoprofen, and etodolac, have direct superoxide scavenging activity.
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PMID:Direct superoxide scavenging activity of nonsteroidal anti-inflammatory drugs: determination by electron spin resonance using the spin trap method. 1125 97

Inflammation causes the induction of cyclooxygenase-2 (Cox-2), leading to the release of prostanoids, which sensitize peripheral nociceptor terminals and produce localized pain hypersensitivity. Peripheral inflammation also generates pain hypersensitivity in neighbouring uninjured tissue (secondary hyperalgesia), because of increased neuronal excitability in the spinal cord (central sensitization), and a syndrome comprising diffuse muscle and joint pain, fever, lethargy and anorexia. Here we show that Cox-2 may be involved in these central nervous system (CNS) responses, by finding a widespread induction of Cox-2 expression in spinal cord neurons and in other regions of the CNS, elevating prostaglandin E2 (PGE2) levels in the cerebrospinal fluid. The major inducer of central Cox-2 upregulation is interleukin-1beta in the CNS, and as basal phospholipase A2 activity in the CNS does not change with peripheral inflammation, Cox-2 levels must regulate central prostanoid production. Intraspinal administration of an interleukin-converting enzyme or Cox-2 inhibitor decreases inflammation-induced central PGE2 levels and mechanical hyperalgesia. Thus, preventing central prostanoid production by inhibiting the interleukin-1beta-mediated induction of Cox-2 in neurons or by inhibiting central Cox-2 activity reduces centrally generated inflammatory pain hypersensitivity.
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PMID:Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. 1126 Jun 97

The very fact that apoptosis and nonsteroidal anti-inflammatory drugs (NSAIDs) can be linked in the same title should tell you that something unusual is happening. The image of NSAIDs among physicians is certainly discordant with that associated with cancer treatment, which usually involves administration of drugs with serious or even life-threatening toxicity. In contrast, the drugs discussed in this review, including selective cyclooxygenase-2 inhibitors, lipoxygenase inhibitors, and novel NSAID derivatives (eg, sulindac sulfone and R-flurbiprofen), offer the promise of oral, nontoxic agents able to control the progression of established prostate cancer and possibly to prevent the development of prostate cancer de novo. NSAIDs were initially developed to suppress inflammation and pain by inhibiting the production of prostaglandin E2 and its metabolites. At first glance, the fact that NSAIDs are active against prostate cancer in laboratory and clinical studies might suggest that prostaglandins play a pivotal role in prostate cancer biology. However, the story is much more complex than that. Although cyclooxygenase-mediated production of prostaglandins appears to play an important role in the biology of prostate cancer, the NSAIDs and derivatives with promising activity against prostate cancer manifest several mechanisms of action that can include direct inhibition of eicosanoid formation, indirect inhibition of eicosanoid formation by inhibiting expression of enzymes involved in eicosanoid synthesis, or by interfering with the function of cyclic guanosine monophosphate.
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PMID:Proapoptotic anti-inflammatory drugs. 1129 99

Rheumatoid arthritis is the paradigmatic immune-mediated inflammatory arthropathy and may be of comparatively recent, New World origin. Apart from the symptom-relieving nonsteroidal anti-inflammatory drugs, whose natural congeners have been in use since antiquity for musculoskeletal pain and inflammation, only a dozen drugs or drug classes--the disease-modifying antirheumatic drugs--are currently in common use in rheumatoid arthritis. Development of these drugs has been a notable achievement of the 20th century. Some were developed serendipitously (glucocorticoids, antimalarials), some were the product of faulty reasoning (gold, D-penicillamine), and others were applied for plausible reasons but whose mechanism remains unproven (sulfasalazine, methotrexate, minocycline). A minority were originally applied on the basis of actions that remain germane to the pathophysiology of rheumatoid arthritis as currently understood (azathioprine, cyclosporine, leflunomide, infliximab, etanercept). Among the latter are the more recently introduced and effective agents. The practical use of these drugs is determined by efficacy-toxicity considerations, which have also driven the recent development of the cyclooxygenase-2-selective nonsteroidal anti-inflammatory drugs.
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PMID:Old and new drugs used in rheumatoid arthritis: a historical perspective. Part 1: the older drugs. 1130 66


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