Background & Aims
Pain and itch are complex symptoms that rely on primary sensory neurons with nerve endings in the skin. These neurons detect both external and endogenous stimuli, including lipids, and one such intriguing bioactive lipid is a linoleic acid metabolite, 9-keto-12,13-epoxy-ocatdecenoate (or EKODE), rich in Western Diets. Here, we elucidate the mechanism by which EKODE activates specific receptors on sensory neurons, leading to the transmission of itch and pain signals.
Methods
We utilized interdisciplinary approaches such as mouse genetics, behavior, mouse chronic itch model, pharmacology, and cell and molecular biology to unveil the mechanism behind chronic itch and acute heat pain hypersensitivity.
Results
Our results demonstrate the role of bioactive lipids in itch and that it is mediated via receptor GPR35 acting upstream of TRPV1/TRPA1 channels. We further showed that neuropeptide BNP plays a key role in neurotransmission. Additionally, we explored the implications of the GPR 35 in mouse models of psoriasis where both itch and pain are prominent symptoms.
Conclusions
Future research into the Linoleic acid lipid metabolites-mediated pathways may unveil novel therapeutic targets for the treatment of these debilitating conditions.
References
Ramsden CE, Domenichiello AF, Yuan ZX, Sapio MR, Keyes GS, Mishra SK, Gross JR, Majchrzak-Hong S, Zamora D, Horowitz MS, Davis JM, Sorokin AV, Dey A, LaPaglia DM, Wheeler JJ, Vasko MR, Mehta NN, Mannes AJ, Iadarola MJA, systems approach for discovering linoleic acid derivatives that potentially mediate pain and itch.Sci Signal. 2017 Aug 22;10(493):