Arachidonic acid containing phosphatidylcholine increases due to microglial activation in ipsilateral spinal dorsal horn following spared sciatic nerve injury.

Tomohiro Banno,Michael Costigan,Dongmin Xu,Hideyuki Arima,Takao Omura,Mitsutoshi Setou,Alban Latremoliere,Yukihiro Matsuyama,Noritaka Masaki,Ayako Okamoto,Ferenc Gallyas

doi:10.1371/journal.pone.0177595

Abstract

Peripheral nerve injury induces substantial molecular changes in the somatosensory system that leads to maladaptive plasticity and cause neuropathic pain. Understanding the molecular pathways responsible for the development of neuropathic pain is essential to the development of novel rationally designed therapeutics. Although lipids make up to half of the dry weight of the spinal cord, their relation with the development of neuropathic pain is poorly understood. We aimed to elucidate the regulation of spinal lipids in response to neuropathic peripheral nerve injury in mice by utilizing matrix-assisted laser desorption/ionization imaging mass spectrometry, which allows visualization of lipid distribution within the cord. We found that arachidonic acid (AA) containing [PC(diacyl-16:0/20:4)+K]+ was increased temporarily at superficial ipsilateral dorsal horn seven days after spared nerve injury (SNI). The spatiotemporal changes in lipid concentration resembled microglia activation as defined by ionized calcium binding adaptor molecule 1 (Iba1) immunohistochemistry. Suppression of microglial function through minocycline administration resulted in attenuation of hypersensitivity and reduces [PC(diacyl-16:0/20:4)+K]+ elevation in the spinal dorsal horn. These data suggested that AA containing [PC(diacyl-16:0/20:4)+K]+ is related to hypersensitivity evoked by SNI and implicate microglial cell activation in this lipid production.

Highlights

Lipids are the most common biomolecules found in the spinal cord making approximately 50% of its dry weight [1]
Phosphatidylcholine (PC) is a major component of most intracellular membranes and is metabolized into downstream signaling lipids, such as phosphatidic acid (PA), diacylglycerol, lyso-PC molecular species (PCs), and arachidonic acid [3]. Lipid molecules such as prostaglandins (PG) [4], lysophosphatidic acid (LPA) [5], and cannabinoids [6] play an important role in the development of chronic pain, notably neuropathic pain which can occur after peripheral nerve injury in patients
We recently demonstrated that after nerve transection alone, arachidonic acid-containing phosphatidylcholine (PC), was significantly increased in the ipsilateral ventral and dorsal horns of the spinal cord [16], no work has been performed on the distribution of phospholipids in the injured spinal cord from preclinical models of neuropathic pain with parallel behavioral analyses

Summary

Introduction

Lipids are the most common biomolecules found in the spinal cord making approximately 50% of its dry weight [1] These diverse molecules are involved in many cellular functions including regulation of physical properties of cellular membrane and neurotransmitter signaling [2]. Phosphatidylcholine (PC) is a major component of most intracellular membranes and is metabolized into downstream signaling lipids, such as phosphatidic acid (PA), diacylglycerol, lyso-PC, and arachidonic acid [3] Lipid molecules such as prostaglandins (PG) [4], lysophosphatidic acid (LPA) [5], and cannabinoids [6] play an important role in the development of chronic pain, notably neuropathic pain which can occur after peripheral nerve injury in patients. It is not known whether PC itself in the spinal cord directly contributes to the development of neuropathic pain

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