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Sci Rep. 2017 Mar 27;7(1):446. doi: 10.1038/s41598-017-00591-0.

The G2A receptor (GPR132) contributes to oxaliplatin-induced mechanical pain hypersensitivity.

Author information

1
Institute of Clinical Pharmacology, pharmazentrum frankfurt/ZAFES, University Hospital, Goethe-University, D-60590, Frankfurt am Main, Germany.
2
Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany.
3
F. M. Kirby Neurobiology Center, Children's Hospital Boston, and Department of Neurobiology, Harvard Medical School, Boston, MA, 02115, USA.
4
Fraunhofer Institute for Molecular Biology and Applied Ecology - Project Group Translational Medicine and Pharmacology (IME-TMP), Frankfurt am Main, Germany.
5
Institute of Clinical Pharmacology, pharmazentrum frankfurt/ZAFES, University Hospital, Goethe-University, D-60590, Frankfurt am Main, Germany. marco.sisignano@med.uni-frankfurt.de.

Abstract

Chemotherapy-induced peripheral neuropathic pain (CIPN) is a common and severe debilitating side effect of many widely used cytostatics. However, there is no approved pharmacological treatment for CIPN available. Among other substances, oxaliplatin causes CIPN in up to 80% of treated patients. Here, we report the involvement of the G-protein coupled receptor G2A (GPR132) in oxaliplatin-induced neuropathic pain in mice. We found that mice deficient in the G2A-receptor show decreased mechanical hypersensitivity after oxaliplatin treatment. Lipid ligands of G2A were found in increased concentrations in the sciatic nerve and dorsal root ganglia of oxaliplatin treated mice. Calcium imaging and patch-clamp experiments show that G2A activation sensitizes the ligand-gated ion channel TRPV1 in sensory neurons via activation of PKC. Based on these findings, we conclude that targeting G2A may be a promising approach to reduce oxaliplatin-induced TRPV1-sensitization and the hyperexcitability of sensory neurons and thereby to reduce pain in patients treated with this chemotherapeutic agent.

PMID:
28348394
PMCID:
PMC5428564
DOI:
10.1038/s41598-017-00591-0
[Indexed for MEDLINE]
Free PMC Article

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