• Claus Dieter Schuh, Sandra Pierre, Andreas Weigert, Benjamin Weichand, Kai Altenrath, Yannick Schreiber, Nerea Ferreiros, Dong Dong Zhang, Jing Suo, Elsa-Marie Treutlein, Marina Henke, Hana Kunkel, Manuel Grez, Rolf Nüsing, Bernhard Brüne, Gerd Geisslinger, and Klaus Scholich.
• Institute of Clinical Pharmacology, Pharmazentrum Frankfurt/ZAFES, Hospital of the Goethe-University, Frankfurt, Germany.
• Pain. 2014 Mar 1;155(3):545-55.

AbstractProstacyclin is an important mediator of peripheral pain sensation. Here, we investigated its potential participation in mediating neuropathic pain and found that prostacyclin receptor (IP) knockout mice exhibited markedly decreased pain behavior. Application of an IP antagonist to the injury site or selective IP deficiency in myeloid cells mimicked the antinociceptive effect observed in IP knockout mice. At the site of nerve injury, IP was expressed in interleukin (IL) 1β-containing resident macrophages, which were less common in IP knockout mice. Local administration of the IP agonist cicaprost inhibited macrophage migration in vitro and promoted accumulation of IP- and IL1β-expressing cells as well as an increase of IL1β concentrations at the application site in vivo. Fittingly, the IL1-receptor antagonist anakinra (IL-1ra) decreased neuropathic pain behavior in wild-type mice but not in IP knockout mice. Finally, continuous, but not single administration, of the cyclooxygenase inhibitor meloxicam early after nerve injury decreased pain behavior and the number of resident macrophages. Thus, early synthesis of prostacyclin at the site of injury causes accumulation of IL1β-expressing macrophages as a key step in neuropathic pain after traumatic injury.Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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