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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-873

Reinold, H; Ahmadi, S; Depner, U B; Layh, B; Heindl, C; Hamza, M; Pahl, A; Brune, K; Narumiya, S; Müller, U; Zeilhofer, H U (2005). Spinal inflammatory hyperalgesia is mediated by prostaglandin E receptors of the EP2 subtype. Journal of Clinical Investigation, 115(3):673-679.

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Abstract

Blockade of prostaglandin (PG) production by COX inhibitors is the treatment of choice for inflammatory pain but is also prone to severe side effects. Identification of signaling elements downstream of COX inhibition, particularly of PG receptor subtypes responsible for pain sensitization (hyperalgesia), provides a strategy for better-tolerated analgesics. Here, we have identified PGE2 receptors of the EP2 receptor subtype as key signaling elements in spinal inflammatory hyperalgesia. Mice deficient in EP2 receptors (EP2-/- mice) completely lack spinal PGE2-evoked hyperalgesia. After a peripheral inflammatory stimulus, EP2-/- mice exhibit only short-lasting peripheral hyperalgesia but lack a second sustained hyperalgesic phase of spinal origin. Electrophysiological recordings identify diminished synaptic inhibition of excitatory dorsal horn neurons as the dominant source of EP2 receptor-dependent hyperalgesia. Our results thus demonstrate that inflammatory hyperalgesia can be treated by targeting of a single PG receptor subtype and provide a rational basis for new analgesic strategies going beyond COX inhibition.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:1 March 2005
Deposited On:11 Feb 2008 12:19
Last Modified:23 Nov 2012 14:32
Publisher:American Society for Clinical Investigation
ISSN:0021-9738
Publisher DOI:10.1172/JCI200523618
PubMed ID:15719070

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