Lipoxins and aspirin-triggered lipoxin inhibit inflammatory pain processing.
Inflammatory conditions can lead to debilitating and persistent pain. This hyperalgesia reflects sensitization of peripheral terminals and facilitation of pain signaling at the spinal level. Studies of peripheral systems show that tissue injury triggers not only inflammation but also a well-orchestrated series of events that leads to reversal of the inflammatory state. In this regard, lipoxins represent a unique class of lipid mediators that promote resolution of inflammation. The antiinflammatory role of peripheral lipoxins raises the hypothesis that similar neuraxial systems may also down-regulate injury-induced spinal facilitation of pain processing. We report that the lipoxin A(4) receptor is expressed on spinal astrocytes both in vivo and in vitro and that spinal delivery of lipoxin A(4), as well as stable analogues, attenuates inflammation-induced pain. Furthermore, activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase in astrocytes, which has been indicated to play an important role in spinal pain processing, was attenuated in the presence of lipoxins. This linkage opens the possibility that lipoxins regulate spinal nociceptive processing though their actions upon astrocytic activation. Targeting mechanisms that counterregulate the spinal consequences of persistent peripheral inflammation provide a novel endogenous mechanism by which chronic pain may be controlled.
Svensson
Camilla I
CI
Department of Anesthesiology, University of California, San Diego, La Jolla, CA 92093, USA. csvensson@ucsd.edu
Zattoni
Michela
M
Serhan
Charles N
CN
D000818:Animals; D001241:Aspirin / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D002351:Carrageenan / Q000633:toxicity; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications; D018836:Inflammation Mediators / Q000378:metabolism; D044045:Lipoxins / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044067:Receptors, Lipoxin / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology
D018836:Inflammation Mediators; D044045:Lipoxins; D044067:Receptors, Lipoxin; C482540:lipoxin A(4) receptor, rat; C040527:lipoxin A4; D002351:Carrageenan; D001241:Aspirin