Spinal inflammatory hyperalgesia is mediated by prostaglandin E receptors of the EP2 subtype
Heiko Reinold, … , Ulrike Müller, Hanns Ulrich Zeilhofer
Heiko Reinold, … , Ulrike Müller, Hanns Ulrich Zeilhofer
Published March 1, 2005
Citation Information: J Clin Invest. 2005;115(3):673-679. https://doi.org/10.1172/JCI23618.
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Article Neuroscience

Spinal inflammatory hyperalgesia is mediated by prostaglandin E receptors of the EP2 subtype

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.

Authors

Heiko Reinold, Seifollah Ahmadi, Ulrike B. Depner, Beate Layh, Cornelia Heindl, May Hamza, Andreas Pahl, Kay Brune, Shuh Narumiya, Ulrike Müller, Hanns Ulrich Zeilhofer

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