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.