TY  - JOUR
A1  - Coste, Ovidiu
A1  - Pierre, Sandra
A1  - Marian, Claudiu
A1  - Brenneis, Christian
A1  - Angioni, Carlo Federico
A1  - Schmidt, Helmut
A1  - Popp, Laura
A1  - Geisslinger, Gerd
A1  - Scholich, Klaus
T1  - Antinociceptive activity of the S1P-receptor agonist FTY720
T2  - Journal of cellular and molecular medicine
N2  - FTY720 is a novel immunosuppressive drug that inhibits the egress of lymphocytes from secondary lymphoid tissues and thymus. In its phosphorylated form FTY720 is a potent S1P receptor agonist. Recently it was also shown that FTY720 can reduce prostaglandin synthesis through the direct inhibition of the cytosolic phospholipase A2 (cPLA2). Since prostaglandins are important mediators of nociception, we studied the effects of FTY720 in different models of nociception. We found that intraperitoneal administration of FTY720 reduced dose-dependently the nociceptive behaviour of rats in the formalin assay. Although the antinociceptive doses of FTY720 were too low to alter the lymphocyte count, prostanoid concentrations in the plasma were dramatically reduced. Surprisingly, intrathecally administered FTY720 reduced the nociceptive behaviour in the formalin assay without altering spinal prostaglandin synthesis, indicating that additional antinociceptive mechanisms beside the inhibition of prostaglandin synthesis are involved. Accordingly, FTY720 reduced also the nociceptive behaviour in the spared nerve injury model for neuropathic pain which does not depend on prostaglandin synthesis. In this model the antinociceptive effect of FTY720 was similar to gabapentin, a commonly used drug to treat neuropathic pain. Taken together we show for the first time that FTY720 possesses antinociceptive properties and that FTY720 reduces nociceptive behaviour during neuropathic pain.
KW  - FTY720
KW  - sphingosine-1-phosphate
KW  - neuropathic pain
KW  - spinal cord
KW  - prostaglandin
Y1  - 2008
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27961
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-279618
UR  - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401143/
SN  - 1582-4934
SN  - 1582-1838
N1  - © 2008 The Authors Journal compilation © 2008 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an Open Access article under the terms of the Creative Commons Attribution Non Commercial License http://creativecommons.org/licenses/by-nc/3.0/ which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
VL  - 12
IS  - 3
SP  - 995
EP  - 1004
PB  - Wiley-Blackwell
CY  - Hoboken, NJ
ER  -