Modulation of Inflammatory Pain by Myeloid FABP5

The initiation and maintenance of pain involves complex neuroimmune interactions, with myeloid cell output finetuning the balance between pronociceptive and antinociceptive signaling. Fatty acid binding protein 5 (FABP5) is a lipid chaperone whose inhibition produces antinociceptive effects in models of inflammatory pain. While FABP5 is highly expressed in myeloid cells that are recruited to sites of inflammation, the contribution of myeloid FABP5 to nociception is unknown. Utilizing myeloid-specific FABP5 conditional knockout (cKO) mice, we demonstrate that FABP5+ myeloid cells infiltrate into the paw following the onset of carrageenan-induced inflammation. However, myeloid cell recruitment was unaffected by FABP5 deletion. FABP5 cKO were characterized by attenuated development of inflammatory thermal hyperalgesia, which was observed throughout the experimental time course and was evident in both sexes. Transcriptomic profiling of myeloid cells obtained from carrageenan injected paws identified numerous differentially expressed genes between FABP5 cKO mice and Flox controls. Notably, FABP5 cKO myeloid cells featured elevated expression of interleukin-10 (IL-10), consistent with previous findings demonstrating that FABP5 deletion polarizes myeloid cells towards an M2-like anti-inflammatory phenotype. Collectively, this study ascribes a new role to myeloid FABP5 in pain modulation and provides additional evidence that the regulation of nociception by FABP5 involves distinct mechanisms across multiple anatomical loci and cell populations.