Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
Type: Journal article
Title: Sphingosine-1-phosphate-induced nociceptor excitation and ongoing pain behavior in mice and humans is largely mediated by S1P3 receptor
Author: Camprubí-Robles, M.
Mair, N.
Andratsch, M.
Benetti, C.
Beroukas, D.
Rukwied, R.
Langeslag, M.
Proia, R.L.
Schmelz, M.
Ferrer Montiel, A.V.
Haberberger, R.V.
Kress, M.
Citation: The Journal of Neuroscience, 2013; 33(6):2582-2592
Publisher: Society for Neuroscience
Issue Date: 2013
ISSN: 0270-6474
Statement of
María Camprubí-Robles, Norbert Mair, Manfred Andratsch, Camilla Benetti, Dimitra Beroukas, Roman Rukwied ... et al.
Abstract: The biolipid sphingosine-1-phosphate (S1P) is an essential modulator of innate immunity, cell migration, and wound healing. It is released locally upon acute tissue injury from endothelial cells and activated thrombocytes and, therefore, may give rise to acute post-traumatic pain sensation via a yet elusive molecular mechanism. We have used an interdisciplinary approach to address this question, and we find that intradermal injection of S1P induced significant licking and flinching behavior in wild-type mice and a dose-dependent flare reaction in human skin as a sign of acute activation of nociceptive nerve terminals. Notably, S1P evoked a small excitatory ionic current that resulted in nociceptor depolarization and action potential firing. This ionic current was preserved in "cation-free" solution and blocked by the nonspecific Cl(-) channel inhibitor niflumic acid and by preincubation with the G-protein inhibitor GDP-β-S. Notably, S1P(3) receptor was detected in virtually all neurons in human and mouse DRG. In line with this finding, S1P-induced neuronal responses and spontaneous pain behavior in vivo were substantially reduced in S1P(3)(-/-) mice, whereas in control S1P(1) floxed (S1P(1)(fl/fl)) mice and mice with a nociceptor-specific deletion of S1P(1)(-/-) receptor (SNS-S1P(1)(-/-)), neither the S1P-induced responses in vitro nor the S1P-evoked pain-like behavior was altered. Therefore, these findings indicate that S1P evokes significant nociception via G-protein-dependent activation of an excitatory Cl(-) conductance that is largely mediated by S1P(3) receptors present in nociceptors, and point to these receptors as valuable therapeutic targets for post-traumatic pain.
Keywords: Ganglia, Spinal
Cells, Cultured
Mice, Inbred C57BL
Mice, Transgenic
Receptors, Lysosphingolipid
Pain Measurement
Double-Blind Method
Rights: ©2013 the authors
DOI: 10.1523/JNEUROSCI.4479-12.2013
Grant ID:
Published version:
Appears in Collections:Environment Institute publications

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.