Macrophage/microglia-producing transient increase of platelet-activating factor is involved in neuropathic pain

Shota Yamamoto; Tomomi Hashidate-Yoshida; Yuki Yoshinari; Takao Shimizu; Hideo Shindou

doi:10.1016/j.isci.2024.109466

Macrophage/microglia-producing transient increase of platelet-activating factor is involved in neuropathic pain

iScience. 2024 Apr 1;27(4):109466. doi: 10.1016/j.isci.2024.109466. eCollection 2024 Apr 19.

Authors

Shota Yamamoto^{1

2}, Tomomi Hashidate-Yoshida¹, Yuki Yoshinari^{1

3}, Takao Shimizu^{4

5}, Hideo Shindou^{1

6}

Affiliations

¹ Department of Lipid Life Science, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan.
² Division of Molecular Neuroimmunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
³ Graduate School of Life Sciences, Showa Women's University, Setagaya-ku, Tokyo, Japan.
⁴ Department of Lipid Signaling, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan.
⁵ Institute of Microbial Chemistry, Setagaya-ku, Tokyo, Japan.
⁶ Department of Medical Lipid Science, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Abstract

Peripheral nerve injury (PNI) induces debilitating neuropathic pain symptoms, such as tactile allodynia. Accumulating evidence suggests that the expression levels of various transcripts and proteins are drastically changed after PNI. Recent lipidome analysis demonstrates increased levels of diverse lipids in chronic pain conditions. We show that PNI transiently increases platelet-activating factor (PAF) levels, a potent inflammatory phospholipid mediator, in the dorsal root ganglia (DRG) and spinal cord. We revealed that macrophage and microglia-specific PAF-producing enzyme LPLAT9/LPCAT2 knockout mice (Cx3cr1^CreERT2;Lpcat2^flox/flox) failed to develop mechanical allodynia and to increase PAF levels in the DRG and spinal cord after PNI. Moreover, we observed the suppression of PNI-induced PAF increase in the spinal cord of PAF receptor knockout mice, indicating a self-amplification loop of PAF production. In conclusion, macrophages and microglia enhance PAF production, contributing to PNI-induced neuropathic pain. Additionally, PAF-PAF receptor signaling is a potential target of neuropathic pain control.

Keywords: Cell biology; Immunology; Neuroscience.