UZH-Logo

Maintenance Infos

Contribution of peripheral versus central EP1 prostaglandin receptors to inflammatory pain


Johansson, T; Narumiya, S; Zeilhofer, H U (2011). Contribution of peripheral versus central EP1 prostaglandin receptors to inflammatory pain. Neuroscience Letters, 495(2):98-101.

Abstract

Prostaglandin E(2) (PGE(2)) is a key mediator of exaggerated pain sensation during inflammation. Drugs targeting the PGE(2) pathway by global inhibition of cyclooxygenases are well established in the treatment of inflammatory pain, but also cause significant unwanted effects. Enzymes downstream of the cyclooxygenases, or prostaglandin receptors are candidate targets possibly enabling therapeutic intervention with potentially fewer side effects. Among the PGE(2) receptors, the EP1 subtype has repeatedly been proposed as a promising target for treatment of inflammatory hyperalgesia. However its involvement in sensitization at specific (peripheral or central) sites has not been thoroughly investigated. Here, we have used mice deficient in the EP1 receptor (EP1(-/-)) to address this issue. EP1(-/-) mice showed normal mechanical and heat sensitivity during baseline conditions. Local subcutaneous PGE(2) injection into one hindpaw, caused thermal and mechanical sensitization in wild-type mice and EP1(-/-) mice. Thermal sensitization in EP1(-/-) mice was less than in wild-type mice while no significant difference was seen for mechanical sensitization. Injection of PGE(2) into the subarachnoid space of the lumbar spinal cord, resulted in a similar mechanical sensitization in EP1(-/-) mice and in wild-type mice, while a tendency towards reduced reaction to noxious heat stimulation was observed in EP1(-/-) mice. These results support a major contribution of EP1 receptors to peripheral heat sensitization, but only a minor role in mechanical sensitization and in spinal heat sensitization by PGE(2). After local subcutaneous zymosan A injection, EP1(-/-) mice showed indistinguishable mechanical and heat sensitization compared with wild-type mice. Taken together, these results suggest that peripheral EP1 receptors contribute significantly to inflammation induced heat pain sensitization while evidence for a contribution to central sensitization was not obtained.

Prostaglandin E(2) (PGE(2)) is a key mediator of exaggerated pain sensation during inflammation. Drugs targeting the PGE(2) pathway by global inhibition of cyclooxygenases are well established in the treatment of inflammatory pain, but also cause significant unwanted effects. Enzymes downstream of the cyclooxygenases, or prostaglandin receptors are candidate targets possibly enabling therapeutic intervention with potentially fewer side effects. Among the PGE(2) receptors, the EP1 subtype has repeatedly been proposed as a promising target for treatment of inflammatory hyperalgesia. However its involvement in sensitization at specific (peripheral or central) sites has not been thoroughly investigated. Here, we have used mice deficient in the EP1 receptor (EP1(-/-)) to address this issue. EP1(-/-) mice showed normal mechanical and heat sensitivity during baseline conditions. Local subcutaneous PGE(2) injection into one hindpaw, caused thermal and mechanical sensitization in wild-type mice and EP1(-/-) mice. Thermal sensitization in EP1(-/-) mice was less than in wild-type mice while no significant difference was seen for mechanical sensitization. Injection of PGE(2) into the subarachnoid space of the lumbar spinal cord, resulted in a similar mechanical sensitization in EP1(-/-) mice and in wild-type mice, while a tendency towards reduced reaction to noxious heat stimulation was observed in EP1(-/-) mice. These results support a major contribution of EP1 receptors to peripheral heat sensitization, but only a minor role in mechanical sensitization and in spinal heat sensitization by PGE(2). After local subcutaneous zymosan A injection, EP1(-/-) mice showed indistinguishable mechanical and heat sensitization compared with wild-type mice. Taken together, these results suggest that peripheral EP1 receptors contribute significantly to inflammation induced heat pain sensitization while evidence for a contribution to central sensitization was not obtained.

Citations

7 citations in Web of Science®
9 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

1 download since deposited on 12 May 2011
0 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:12 May 2011 13:11
Last Modified:05 Apr 2016 14:54
Publisher:Elsevier
ISSN:0304-3940
Publisher DOI:10.1016/j.neulet.2011.03.046
PubMed ID:21440042
Permanent URL: http://doi.org/10.5167/uzh-48051

Download

[img]
Content: Published Version
Filetype: PDF - Registered users only
Size: 1MB
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations