FTY720 Attenuates Neuropathic Pain after Spinal Cord Injury by Decreasing Systemic and Local Inflammation in a Rat Spinal Cord Compression Model
Open Access
- 1 August 2020
- journal article
- research article
- Published by Mary Ann Liebert Inc in Journal of Neurotrauma
- Vol. 37 (15), 1720-1728
- https://doi.org/10.1089/neu.2019.6905
Abstract
Neuropathic pain severely impairs rehabilitation and quality of life after spinal cord injury (SCI). The sphingosine-1-phosphate receptor agonist, FTY720, plays an important protective role in neuronal injury. This study aims to examine the effects of FTY720 in a rat acute SCI model, focusing on neuropathic pain. Female rats with SCI induced by 1-min clip compression were administered vehicle or 1.5 mg/kg of FTY720 24 h after the injury. Using the mechanical nociceptive threshold test, we monitored neuropathic pain and performed histological analysis of the pain pathway, including the μ opioid receptor (MOR), hydroxytryptamine transporter (HTT), and calcitonin gene-related peptide (CGRP). Motor score, SCI lesion volume, residual motor axons, inflammatory response, glial scar, and microvascular endothelial dysfunction were also compared between the two groups. FTY720 treatment resulted in significant attenuation of post-traumatic neuropathic pain. It also decreased systemic and local inflammation, thereby reducing the damaged areas and astrogliosis and resulting in motor functional recovery. Whereas there was no difference in the CGRP expression between the two groups, FTY720 significantly preserved the MOR in both the caudal and rostral areas of the spinal dorsal horn. Whereas HTT was preserved in the FTY720 group, it was significantly increased in the rostral side and decreased in the caudal side of the injury in the vehicle group. These results suggest that FTY720 ameliorates post-traumatic allodynia through regulation of neuroinflammation, maintenance of the blood–brain barrier, and inhibition of glial scar formation, thereby preserving the connectivity of the descending inhibitory pathway and reducing neuropathic pain.Keywords
This publication has 37 references indexed in Scilit:
- Sphingolipids in cardiovascular and cerebrovascular systems: Pathological implications and potential therapeutic targetsWorld Journal of Cardiology, 2013
- The Relationship between Localized Subarachnoid Inflammation and Parenchymal Pathophysiology after Spinal Cord InjuryJournal of Neurotrauma, 2012
- FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P 1 ) modulationProceedings of the National Academy of Sciences, 2010
- FTY720 Reduces Inflammation and Promotes Functional Recovery after Spinal Cord InjuryJournal of Neurotrauma, 2009
- The immunomodulatory sphingosine 1-phosphate analog FTY720 reduces lesion size and improves neurological outcome in a mouse model of cerebral ischemiaBiochemical and Biophysical Research Communications, 2009
- TRANSPLANTED BONE MARROW STROMAL CELLS PROMOTE AXONAL REGENERATION AND IMPROVE MOTOR FUNCTION IN A RAT SPINAL CORD INJURY MODELNeurosurgery, 2009
- Antinociceptive activity of the S1P‐receptor agonist FTY720Journal of Cellular and Molecular Medicine, 2008
- Symptom Burden in Persons With Spinal Cord InjuryArchives of Physical Medicine and Rehabilitation, 2007
- Abnormal expansion of naïve B lymphocytes after unrelated cord blood transplantation - a case reportClinical and Laboratory Haematology, 2006
- A Sensitive and Reliable Locomotor Rating Scale for Open Field Testing in RatsJournal of Neurotrauma, 1995