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Analgesic strategies beyond the inhibition of cyclooxygenases


Zeilhofer, H U; Brune, K (2006). Analgesic strategies beyond the inhibition of cyclooxygenases. Trends in Pharmacological Sciences, 27(9):467-474.

Abstract

Blocking the formation of prostaglandins with cyclooxygenase (COX) inhibitors has been the treatment of choice for inflammatory pain for more than a century. Although these agents provide profound pain relief, their long-term use is hampered by severe side-effects, mainly ulceration of the upper gastrointestinal tract. The development of COX-2-selective inhibitors ("coxibs") has significantly reduced gastrointestinal toxicity, but evidence from controlled clinical trials and experimental studies indicates that the use of coxibs has a significant cardiovascular risk. Recently, signalling elements downstream of COX-2 inhibition have been identified, which offer a great diversity of possible targets. This review focuses on prostaglandin E synthases, prostaglandin receptors and downstream effectors of prostaglandins in the PNS and CNS, including transient receptor potential channels, tetrodotoxin-resistant Na(+) channels and inhibitory glycine receptors. These novel targets should enable inflammatory pain to be treated with improved specificity and, possibly, fewer side-effects.

Blocking the formation of prostaglandins with cyclooxygenase (COX) inhibitors has been the treatment of choice for inflammatory pain for more than a century. Although these agents provide profound pain relief, their long-term use is hampered by severe side-effects, mainly ulceration of the upper gastrointestinal tract. The development of COX-2-selective inhibitors ("coxibs") has significantly reduced gastrointestinal toxicity, but evidence from controlled clinical trials and experimental studies indicates that the use of coxibs has a significant cardiovascular risk. Recently, signalling elements downstream of COX-2 inhibition have been identified, which offer a great diversity of possible targets. This review focuses on prostaglandin E synthases, prostaglandin receptors and downstream effectors of prostaglandins in the PNS and CNS, including transient receptor potential channels, tetrodotoxin-resistant Na(+) channels and inhibitory glycine receptors. These novel targets should enable inflammatory pain to be treated with improved specificity and, possibly, fewer side-effects.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:September 2006
Deposited On:26 Mar 2009 11:35
Last Modified:05 Apr 2016 12:31
Publisher:Elsevier
ISSN:0165-6147
Publisher DOI:10.1016/j.tips.2006.07.007
PubMed ID:16876882
Permanent URL: http://doi.org/10.5167/uzh-4693

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