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.