Inflammopharmacology
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This review attempts to bring together information from a large number of recent studies on the clinical uses, safety and pharmacological properties of ibuprofen. Ibuprofen is widely used in many countries for the relief of symptoms of pain, inflammation and fever. The evidence for modes of action of ibuprofen are considered in relation to its actions in controlling inflammation, pain and fever, as well as the adverse effects of the drug. ⋯ This assessment of the safety and benefits of ibuprofen can be summarized thus: (1) Ibuprofen at OTC doses has low possibilities of serious GI events, and little prospect of developing renal and associated CV events. Ibuprofen OTC does not represent a risk for developing liver injury especially the irreversible liver damage observed with paracetamol and the occasional liver reactions from aspirin. (2) The pharmacokinetic properties of ibuprofen, especially the short plasma half-life of elimination, lack of development of pathologically related metabolites (e.g. covalent modification of liver proteins by the quinine-imine metabolite of paracetamol or irreversible acetylation of biomolecules by aspirin) are support for the view that these pharmacokinetic and notably metabolic effects of ibuprofen favour its low toxic potential. (3) The multiple actions of ibuprofen in controlling inflammation combine with moderate inhibition of COX-1 and COX-2 and low residence time of the drug in the body may account for the low GI, CV and renal risks from ibuprofen, especially at OTC doses.
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Pain is recognized as a multifactorial sensory experience that is wholly unpleasant. It can vary in intensity from mild to severe and its duration can be anything from transient to persistent. ⋯ As a consequence of the assembly of this new body of evidence there are clear pointers that direct our attention to receptors, signaling pathways, enzymes and ion channels that all have the potential to be targets for novel, effective analgesics. The purpose of this review is to highlight some of the knowledge that has been assembled on this subject in recent years.
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Inflammopharmacology · Feb 2009
Development and characterisation of a novel animal model of prostate inflammation-induced chronic pelvic pain.
Chronic pelvic pain due to prostate inflammation is a significant clinical problem. In the current study we developed and validated an animal model of inflammation-induced pelvic pain (NIH category IIIA). 3% carrageenan was injected into the ventral prostate in SD rats. At different time points (before and after 48 h, 72 h and 1 wk of injection), radiant heat and von Frey filaments (mechanical stimuli) were applied to different pelvic areas. ⋯ Inflamed animals showed a significant reduction in mechanical threshold (mechanical allodynia) at 72 h and 1 wk, and a significant reduction in heat threshold (thermal hyperalgesia) in the scrotal skin, compared to sham. Morphine (5 mg/kg., i.p.) significantly reduced both heat hyperalgesia and mechanical allodynia. It is expected that this novel model will prove to be useful in studying the neurobiological mechanisms of male pelvic pain.
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Inflammopharmacology · Feb 2008
Anti-inflammatory effect of alpha, beta-Amyrin, a pentacyclic triterpene from Protium heptaphyllum in rat model of acute periodontitis.
This study was aimed to evaluate the anti-inflammatory potential of triterpene alpha, beta-amyrin in rats on acute phase periodontitis. Periodontitis was induced by ligature placement around the maxillary right second molar tooth. Rats (n = 8/group) were pretreated with alpha, beta-amyrin (5 and 10 mg/kg, p. o.), two hours before the induction of periodontal inflammation. ⋯ Rats were sacrificed at 24 h, and the gingival tissue analysed for myeloperoxidase (MPO) and thiobarbituric acid-reactive substances (TBARS), as measures of neutrophil influx and lipid-peroxidation, respectively alpha, beta-Amyrin as well as dexamethasone significantly inhibited the periodontitis-associated increases of TNF-alpha, and the gingival MPO and TBARS. alpha, beta-Amyrin effect was more prominent at 5 mg/kg. Lumiracoxib manifested varied influence on the studied parameters. These results provide evidence to show that alpha, beta-Amyrin retards acute inflammation in rat model of periodontitis and warrant further study on its efficacy to prevent chronic periodontitis-associated bone loss.
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Inflammopharmacology · Aug 2007
Interaction of local anaesthetics with lipid membranes under inflammatory acidic conditions.
The clinical fact that local anaesthetics do not successfully work in the patients with inflammation has been generally interpreted on the basis of inflamed tissue acidification. In order to verify this hypothesis, the interaction of local anaesthetics with lipid membranes was studied by determining the drug-induced changes of membrane physicochemical property (membrane fluidity) at different pH covering inflammatory acidic conditions. At clinically relevant concentrations, lidocaine, procaine, prilocaine and bupivacaine fluidized 1,2-dipalmitoylphosphatidylcholine membranes with the potency decreased with lowering the pH from 7.9 to 5.9. ⋯ Cationic lidocaine was effective in fluidizing anionic phosphatidylserine and cardiolipin membranes at pH 6.4, but not zwitterionic phospholipid membranes, whereas it was ineffective on any membranes at pH 2.0 where membrane acidic phospholipids were not ionized. Local anaesthetics are considered to form the ion-pairs specifically with counter-ionic phospholipids and act on the membranes of nerve cells even under inflammatory acidic conditions. The drug and membrane interaction causable in inflamed tissue acidification does not support the conventional theory on the local anaesthetic failure associated with inflammation.