Background and objectives FTY720 ((2-amino-2-)2-[4-octylphenyl]ethyl)-1,3-propanediol) is an Food and Drug Administration (FDA)-approved immunomodulatory drug for treating multiple sclerosis. It inhibits lymphocyte egression from lymphoid tissues by downregulating sphingosine-1 phosphate receptor (S1PR). To date, there has been no study on the effects of FTY720 on the chronic stage of the complex regional pain syndrome (CRPS) rodent model, despite its antiallodynic effect in previous studies. Thus, the aim of this study is to investigate the effect of FTY720 in a chronic stage of the CRPS mouse model.
Method The authors used a mouse model of CRPS, involving tibia fracture/cast immobilization, to test the efficacy of intrathecal FTY720 (2.5 or 25 ng daily; 6 days) or vehicle during the chronic (7 weeks after fracture) stage of CRPS.
Results Intrathecal recombinant FTY720 administration was antiallodynic in the chronic stage of the CRPS mouse model, and such an effect of FTY720 developed by modulating astrocyte activation in the spinal cord. Additionally, according to the in vitro data, the FTY720 treatment inhibited S1P-induced increase in the nitric oxide production and suppression of the NF-κB pathway, by inhibiting the phosphorylation of NF-κB/p65 in astrocytes without toxic effect on astrocytes.
Conclusion Collectively, these results demonstrate that intrathecally administered FTY720 attenuates mechanical allodynia in the chronic stage of the CRPS mouse model.
- chronic pain: complex regional pain syndrome
- pain medicine
- animal studies
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BJL and JYK are equivalent first authors.
BJL and JYK contributed equally.
Contributors BJL and JYK: writing manuscript. H-JC: analysis of data, experiment. DP: study concept and design, analysis of data, and critical revision of manuscriptfor intellectual content.
Funding This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF- 2017R1D1A1B03033127).
Disclaimer No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the authors or upon any organization with which the authors are associated.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request. All free text entered below will be published.