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

Early Mechanistic Events Induced by Low Molecular Weight Polycyclic Aromatic Hydrocarbons in Mouse Lung Epithelial Cells: A Role for Eicosanoid Signaling

“…Phosphatidylcholine, perhaps the most wellcharacterized phospholipid, is hydrolyzed directly by cPLA 2 to remove a fatty acid group to produce lysophosphatidylcholine, and was shown to be associated significantly with exposure to the binary PAH mixture (Figure 7) and increased primarily at 0.5 and 4 h after exposure (Figure 9). In addition, the top PC identified in Figure 8 (PC 36:4) has also been specifically linked to AA production (Banno et al, 2017), providing further evidence in support of our findings herein. Phospholipids, such as PC, LysoPC, PE, and LysoPE, were upregulated in the HepG2 cell line exposed to PAHs and SCCP and analyzed via metabolomics methods (Wang et al, 2018).…”

“…Figure 8 depicts those significant metabolites that were identified at the time points that the cPLA 2 protein was upregulated categorized by chain length of the phospholipids. Interestingly, one of the metabolites was a chain length for phosphatidylcholine, PC 36:4, that is known to be cleaved to AA (Banno et al, 2017).…”

Identification of the key genes associated with neuropathic pain

“…The sciatic nerve was only injured in the CCI-Ipsi group, not the CCI-Contra or Sham-Ipsi group, and the nerve was only exposed in the Sham-Ipsi group. Sciatic nerve injury induces the inflammatory response in the ipsilateral spinal cord, whereas the contralateral spinal cord was not, compared with the sham group, as previously reported ( 46 ). Nerve injury induces a set of progressive alterations in ipsilateral spinal cord microglia with increased secretion of cytokines.…”

Inhibiting spinal secretory phospholipase A2 after painful nerve root injury attenuates established pain and spinal neuronal hyperexcitability by altering spinal glutamatergic signaling

“…[35][36][37][38][39] AA concentrations increase in pain states, including preferentially only in the dorsal horn ipsilateral to neural injury. 40 Moreover, inhibiting AA production by the cPLA 2 inhibitor, AACOCF3, after chronic sciatic nerve constriction prevents the onset of pain. 25 Together, these findings suggest that inhibiting generation of bioactive lipids could provide pain relief; however, since both the sPLA 2 and cPLA 2 isoforms hydrolyze phospholipids, with cPLA 2 implicated for primary AA production, 25,41,42 it is unknown if inhibiting either or both isoforms attenuates neuropathic pain.…”