Oxidized Lipids in Persistent Pain States

Abstract

Chemotherapy, nerve injuries, or diseases like multiple sclerosis can cause pathophysiological processes of persistent and neuropathic pain. Thereby, the activation threshold of ion channels is reduced in peripheral sensory neurons to normally noxious stimuli like heat, cold, acid, or mechanical due to sensitization processes. This leads to enhanced neuronal activity, which can result in mechanical allodynia, cold allodynia, thermal hyperalgesia, spontaneous pain, and may initiate persistent and neuropathic pain. The treatment options for persistent and neuropathic pain patients are limited; for about 50% of them, current medication is not efficient due to severe side effects or low response to the treatment. Therefore, it is of special interest to find additional treatment strategies. One approach is the control of neuronal sensitization processes. Herein, signaling lipids are crucial mediators and play an important role during the onset and maintenance of pain. As preclinical studies demonstrate, lipids may act as endogenous ligands or may sensitize transient receptor potential (TRP)-channels. Likewise, they can cause enhanced activity of sensory neurons by mechanisms involving G-protein coupled receptors and activation of intracellular protein kinases. In this regard, oxidized metabolites of the essential fatty acid linoleic acid, 9- and 13-hydroxyoctadecadienoic acid (HODE), their dihydroxy-metabolites (DiHOMEs), as well as epoxides of linoleic acid (EpOMEs) and of arachidonic acid (EETs), as well as lysophospholipids, sphingolipids, and specialized pro-resolving mediators (SPMs) have been reported to play distinct roles in pain transmission or inhibition. Here, we discuss the underlying molecular mechanisms of the oxidized linoleic acid metabolites and eicosanoids. Furthermore, we critically evaluate their role as potential targets for the development of novel analgesics and for the treatment of persistent or neuropathic pain.

Biofilm Derived Oxylipin Mediated Autoimmune Response in Breast Implant Subjects

“…Oxidized lipids have been associated with pain and inflammatory conditions 58 . Pain reported as arthralgia and myalgia are common in BII.…”

Sciadonic acid derived from pine nuts as a food component to reduce plasma triglycerides by inhibiting the rat hepatic Δ9-desaturase

“…9-HODE and 13-HODE were also described as biomarkers of post-exercise inflammation since their concentrations increase following prolonged and intensive exercise 39 . They were incriminated in neuropathic pain, particularly concerning mechanical allodynia and thermal hyperalgesia 40 . In breast cancer, HODEs were the most important oxylipin species upregulated in plasma of cancer patients 41 whereas they were lowered in serum of colorectal cancer patients 42 .…”

The Lipid Receptor G2A (GPR132) Mediates Macrophage Migration in Nerve Injury-Induced Neuropathic Pain

“…This interaction is known to modulate neuronal ion channels, such as the transient receptor potential vanilloid 1 (TRPV1) channel, thereby altering pain perception during neuropathic pain [ 6 , 12 , 13 ]. In nerve injury-induced neuropathic pain during the process of neuroimmune communication, signaling lipids play an important role and several lipid receptors have been identified as crucial mediators of onset, maintenance and resolution of different pathological pain states [ 15 ]. The linoleic acid metabolite 9-hydroxyoctadecadienoic acid (9-HODE) is the ligand of the G-protein coupled receptor G2A (GPR132), which is known to sensitize TRPV1 via G q and activation of protein kinase C (PKC) [ 15 , 16 , 17 ].…”

“…In nerve injury-induced neuropathic pain during the process of neuroimmune communication, signaling lipids play an important role and several lipid receptors have been identified as crucial mediators of onset, maintenance and resolution of different pathological pain states [ 15 ]. The linoleic acid metabolite 9-hydroxyoctadecadienoic acid (9-HODE) is the ligand of the G-protein coupled receptor G2A (GPR132), which is known to sensitize TRPV1 via G q and activation of protein kinase C (PKC) [ 15 , 16 , 17 ]. G2A belongs to the group of proton-sensing GPCRs and is expressed in TRPV1-positive primary sensory neurons, but mainly in immune cells [ 18 , 19 ].…”