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

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.

• Authors: Tomohiro Banno, Takao Omura, Noritaka Masaki, Hideyuki Arima, Dongmin Xu, Ayako Okamoto, Michael Costigan, Alban Latremoliere, Yukihiro Matsuyama, Mitsutoshi Setou
• Journal: PloS one (PLoS One) Vol. 12 Issue 5 Pg. e0177595 ( 2017) ISSN: 1932-6203 [Electronic] United States
• PMID: 28542572 (Publication Type: Journal Article)

Chemical References

• Aif1 protein, mouse
• Calcium-Binding Proteins
• Microfilament Proteins
• Phosphatidylcholines
• Arachidonic Acid
• Minocycline

Topics

• Animals
• Arachidonic Acid (metabolism)
• Calcium-Binding Proteins (metabolism)
• Lipid Metabolism (drug effects)
• Male
• Mice
• Mice, Inbred C57BL
• Microfilament Proteins (metabolism)
• Microglia (drug effects, metabolism)
• Minocycline (pharmacology)
• Neuralgia (etiology, metabolism)
• Phosphatidylcholines (metabolism)
• Sciatic Nerve (injuries)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Spinal Cord Dorsal Horn (drug effects, metabolism)