Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016053 (fibromyalgia)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serotonin antagonists show impressive analgesic efficacy in rheumatoid arthritis, osteoarthritis (OA) or fibromyalgia; however, this effect is not well understood. We examined the mechanism of serotonin-induced inflammation and its antagonists in OA. Serotonin receptor subtypes and COX-2 were analysed by RT-PCR from synovial tissue. Serum-free cultures were stimulated with 10 muM serotonin and/or the antagonists ketanserin (5-HT(2A)), tropisetron (5-HT(3)) and parecoxib (COX-2). Prostaglandin E(2) (PGE(2)), tumour necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta) and leukotriene B4 (LTB4) were measured by an immunoassay in the supernatants. RT-PCR results showed mRNA for 5-HT(2A) and 5-HT(3) receptors, and COX-2. PGE(2) in the supernatants increased by 261.2% +/- 56.7 (mean +/- SEM; P = 0.007) in response to serotonin. TNF-alpha, IL-1beta and LTB4 levels did not change. Ketanserin, tropisetron and parecoxib suppressed PGE(2). The serotonin-induced PGE(2) overexpression appeared thus to be mediated by 5-HT(2A) and 5-HT(3) receptors. This activation might involve COX-2. The findings may explain the potent benefit of 5-HT(3) antagonists.
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PMID:Serotonin mediates PGE2 overexpression through 5-HT2A and 5-HT3 receptor subtypes in serum-free tissue culture of macrophage-like synovial cells. 1836 10

This review focuses on newer medications for the treatment of pain as well as on new guidelines and indications for the use of established medications. With regard to classical analgesics, the use of non-opioids and opioids is reviewed. Here are relevant new data on the use of the old substance acetaminophen as well as on non-selective non-steroidal anti-inflammatory drugs (NSAIDs) and the newer COX-2 selective agents, which continue to be misunderstood. Amongst the opioids the new compound tapentadol with a new mechanism of action is presented as well as a number of new opioid preparations aiming to increase speed of onset of effect and to reduce abuse and diversion. Many medications, which were not originally developed to treat pain, are now used as components of multimodal analgesia or in specific indications. Here are of relevance anticonvulsants such as pregabalin and gabapentin, which were initially used for neuropathic pain, but are now used successfully in a wide range of indications from postoperative pain to fibromyalgia. The reason for this increased range of indications is the realization of the relevance of central sensitization processes for all pain states. Similarly, the use of antidepressants and the old dissociative anesthetic ketamine is increasing for the same reasons. Calcitonin has also found some new indications in difficult to treat pain conditions, while the discussion on the role of cannabinoids in pain management continues, partially driven by political issues. For localized neuropathic pain, there is increasing interest in topical preparations such as lidocaine and capsaicin patches, in particular in view of their minimal systemic adverse effects. Overall, recent advances in the pharmacological management of pain are not so much the result of new 'miracle' drugs, but new preparations and new ways to use old drugs in a variety of settings, often as components of a multimodal approach to pain relief.
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PMID:Recent advances in the pharmacological management of acute and chronic pain. 2584 6

Lipopolysaccharide (LPS) induces hyperthermia accompanied by various other systemic inflammatory symptoms. The rodents exposed to repeated cold (RC) stress according to a specific schedule are useful as experimental models for autonomic imbalance or fibromyalgia. It is now proven that RC-stressed mice exhibit tolerance to LPS, we examined thermal responses to LPS challenge in RC-stressed mice by monitoring core temperature using the telemetry system. Systemic administration of LPS caused bimodal hyperthermic responses in RC-stressed and unstressed mice. The magnitude of the LPS-induced hyperthermia was greater in RC-stressed mice than in unstressed mice. The RC stress-induced enhancement of hyperthermic responses to LPS was abolished by pretreatment with diclofenac, which is a cyclooxygenase (COX) inhibitor. LPS did not significantly increase COX-2 protein levels in the lung or hypothalamus of RC-stressed or unstressed mice. RC stress did not alter baseline serum corticosterone levels or their increases in response to LPS challenge. These results suggest that RC stress enhances the susceptibility of mice to LPS challenge, leading to greater prostanoid-dependent hyperthermia, which might contribute to tolerance to LPS in RC-stressed mice.
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PMID:Enhanced Hyperthermic Responses to Lipopolysaccharide in Mice Exposed to Repeated Cold Stress. 2804 12