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

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.

• Authors: Vijayan Gangadharan, Deepitha Selvaraj, Martina Kurejova, Christian Njoo, Simon Gritsch, Dagmar Škoricová, Heinz Horstmann, Stefan Offermanns, Andrew J Brown, Thomas Kuner, Anke Tappe-Theodor, Rohini Kuner
• Journal: Pain (Pain) Vol. 154 Issue 12 Pg. 2801-2812 (Dec 2013) ISSN: 1872-6623 [Electronic] United States
• PMID: 23973358 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Chemical References

• Lysophospholipids
• Phospholipids
• lysophosphatidylinositol
• GTP-Binding Proteins
• GTP-Binding Protein alpha Subunits, G12-G13
• GTP-Binding Protein alpha Subunits, Gq-G11

Topics

• Animals
• Dose-Response Relationship, Drug
• GTP-Binding Protein alpha Subunits, G12-G13 (metabolism)
• GTP-Binding Protein alpha Subunits, Gq-G11 (metabolism)
• GTP-Binding Proteins (metabolism)
• Lysophospholipids (pharmacology, physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Nociception (drug effects, physiology)
• Phospholipids (pharmacology, physiology)
• Sensory Receptor Cells (drug effects, physiology)
• Signal Transduction (drug effects, physiology)