title: Prostacyclin mediates neuropathic pain through interleukin 1β-expressing resident macrophages.
abstract: Prostacyclin 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.
authors: Institute of Clinical Pharmacology, Pharmazentrum Frankfurt/ZAFES, Hospital of the Goethe-University, Frankfurt, Germany Institute of Biochemistry I, Goethe-University, Frankfurt, Germany Institute of Biomedical Research, Georg-Speyer-Haus, Frankfurt, Germany.
authors: Claus Dieter
authors: CD
authors: Schuh
authors: Sandra
authors: S
authors: Pierre
authors: Andreas
authors: A
authors: Weigert
authors: Benjamin
authors: B
authors: Weichand
authors: Kai
authors: K
authors: Altenrath
authors: Yannick
authors: Y
authors: Schreiber
authors: Nerea
authors: N
authors: Ferreiros
authors: Dong Dong
authors: DD
authors: Zhang
authors: Jing
authors: J
authors: Suo
authors: Elsa-Marie
authors: EM
authors: Treutlein
authors: Marina
authors: M
authors: Henke
authors: Hana
authors: H
authors: Kunkel
authors: Manuel
authors: M
authors: Grez
authors: Rolf
authors: R
authors: Nüsing
authors: Bernhard
authors: B
authors: Brüne
authors: Gerd
authors: G
authors: Geisslinger
authors: Klaus
authors: K
authors: Scholich
mesh_terms: D000818:Animals; D011464:Epoprostenol / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D053583:Interleukin-1beta / Q000096:biosynthesis*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009437:Neuralgia / Q000378:metabolism* / Q000473:pathology
chemical_list: D053583:Interleukin-1beta; D011464:Epoprostenol
keywords: Cyclooxygenase; Interleukin 1β; Macrophages; Neuropathic pain; Prostacyclin