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Pain. 2013 Dec;154(12):2801-12. doi: 10.1016/j.pain.2013.08.019. Epub 2013 Aug 22.

A novel biological role for the phospholipid lysophosphatidylinositol in nociceptive sensitization via activation of diverse G-protein signalling pathways in sensory nerves in vivo.

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  • 1Institute of Pharmacology, Heidelberg University, Heidelberg 69120, Germany.

Abstract

The rich diversity of lipids and the specific signalling pathways they recruit provides tremendous scope for modulation of biological functions. Lysophosphatidylinositol (LPI) is emerging as a key modulator of cell proliferation, migration, and function, and holds important pathophysiological implications due to its high levels in diseased tissues, such as in cancer. Here we report a novel role for LPI in sensitization of peripheral sensory neurons, which was evident as exaggerated sensitivity to painful and innocuous pressure. Histopathological analyses indicated lack of involvement of myelin pathology and immune cell recruitment by LPI. Using pharmacological and conditional genetic tools in mice, we delineated receptor-mediated from non-receptor-mediated effects of LPI and we observed that GPR55, which functions as an LPI receptor when heterologously expressed in mammalian cells, only partially mediates LPI-induced actions in the context of pain sensitization in vivo; we demonstrate that, in vivo, LPI functions by activating Gα(13) as well as Gα(q/11) arms of G-protein signalling in sensory neurons. This study thus reports a novel pathophysiological function for LPI and elucidates underlying molecular mechanisms.

Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

KEYWORDS:

Cancer pain; G-proteins; GPR55; LPI; Peripheral sensitization

PMID:
23973358
[PubMed - indexed for MEDLINE]
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