Antinociceptive activity of the S1P‐receptor agonist FTY720
Open Access
- 21 May 2008
- journal article
- Published by Wiley in Journal of Cellular and Molecular Medicine
- Vol. 12 (3), 995-1004
- https://doi.org/10.1111/j.1582-4934.2008.00160.x
Abstract
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.Keywords
This publication has 36 references indexed in Scilit:
- Involvement of Sphingosine-1-Phosphate in Glutamate Secretion in Hippocampal NeuronsMolecular and Cellular Biology, 2007
- Mechanisms of Neuropathic PainNeuron, 2006
- The immunosuppressant drug FTY720 inhibits cytosolic phospholipase A2 independently of sphingosine-1-phosphate receptorsBlood, 2006
- Intracellular sphingosine 1‐phosphate mediates the increased excitability produced by nerve growth factor in rat sensory neuronsThe Journal of Physiology, 2006
- Medications for neuropathic pain: current trendsNeurological Sciences, 2006
- Sphingosine 1-phosphate and its receptors: an autocrine and paracrine networkNature Reviews Immunology, 2005
- Pharmacodynamics, pharmacokinetics, and safety of multiple doses of FTY720 in stable renal transplant patients: a multicenter, randomized, placebo-controlled, phase I studyTransplantation, 2003
- Sphingosine 1-Phosphate in Amniotic Fluid Modulates Cyclooxygenase-2 Expression in Human Amnion-derived WISH CellsPublished by Elsevier BV ,2003
- The Immune Modulator FTY720 Targets Sphingosine 1-Phosphate ReceptorsJournal of Biological Chemistry, 2002
- The Novel Anticonvulsant Drug, Gabapentin (Neurontin), Binds to the α2δ Subunit of a Calcium ChannelJournal of Biological Chemistry, 1996