Figure 3.

The proalgesic role of oxidized phospholipids and therapeutic options to target OxPL. Display of representative terminals of nociceptors, the first neuron in the pain pathway, found in peripheral tissue. (A) Inflammation attracts immune cells invading the tissue, e.g., in arthritis. Especially neutrophils and macrophages release reactive oxygen species (ROS). They oxidize lipids like those found in the plasma membrane (purple circle). The resulting oxidized phospholipids (OxPL) activate non-selective, excitatory ion channels like transient receptor potential ankyrin 1 (TRPA1) or transient receptor potential vanilloid 1 (TRPV1). Activation of TRP channels leads to a subsequent activation of voltage gated sodium channels (Na_V) and the release of proalgesic molecules like calcitonin gene related peptides (CGRP). Action potentials are induced and propagated along the pain pathways, resulting in pain perception. (B) Treatment with monoclonal E06 antibodies or with the ApoA-I mimetic peptide D-4F scavenge OxPL and thereby reduce nociceptor firing, pain and inflammation. Created with biorender.com^©.