Anti-inflammatory lipid mediators help put out flames at an injury site. On page 245, Svensson and colleagues now report that these lipids switch off pain signals in the spinal cord as well.
Pain occurs when neurons in the periphery get stimulated by tissue damage or inflammatory signals such as prostaglandins (PGs). PGs, produced by neutrophils at the injury site, bind to their receptors on peripheral nerve terminals and trigger a pain message to the central nervous system (CNS). Nonneuronal cells of the CNS such as astrocytes and microglia get turned on by the incoming message and produce yet more PGs and inflammatory cytokines that further amplify the pain signal.
Back at the injury site, pain begins to ease when lipoxin production starts. Lipoxins stop inflammation in several ways. These include enhancing the production of anti-inflammatory cytokines, preventing the recruitment of more neutrophils, and activating macrophages to clean up the mess.
Svensson et al. now report that lipoxins can also act in the CNS. They find that astrocytes express receptors for lipoxin. When lipoxin was injected systemically or directly into the spine, pain was relieved. Receptor activation, Svensson suggests, might suppress the formation of pro-inflammatory factors in the astrocytes.
Many common pain relievers block PG production by chemically inhibiting the PG-producing enzyme. Although Svensson appreciates the usefulness of aspirin in combating all manner of aches and pains, she speculates that the wide range of targets downstream of lipoxin might make lipoxin-induced pain management a better strategy.