Fat nerves keep pain at bay

Abstract

Inflammatory pain is a debilitating condition and a severe health burden; physiologically, it is a complex phenomenon with multiple contributing mechanisms. A new study published in The EMBO Journal reports that tissue inflammation results in local depletion of cholesterol in nociceptive nerves, causing a loss of lipid raft localization of a sodium channel Na_v1.9 and, ultimately, resulting in potentiation of its activity. The discovered effect contributes to the inflammatory overexcitability of peripheral nociceptive nerve terminals resulting in inflammatory hyperalgesia. Topical application of cholesterol‐containing gels was able to offset this inflammatory pain mechanism thereby opening a novel avenue for therapeutic intervention.

Figure 1. Schematic of the antianalgesic effect of cholesterol

Inflammation induces ROS‐dependent local depletion of cholesterol in nociceptive nerves, causing a loss of lipid raft localization of Na_v1.9 and potentiation of its activity. This, in turn, contributes to the inflammatory overexcitability of peripheral nociceptive nerve terminals resulting in hyperalgesia. Topical application of cholesterol‐containing gels restores the status quo.