Contributions
Abstract: EP1464
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 13 Experimental models
Background and aims: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that causes different debilitating symptoms including neuropathic pain in many patients (47%)1. Among current treatments, fingolimod, a non-selective sphingosine-1-phosphate (S1P) receptor modulator showed promising effect on MS outcome. In the same time, the S1P pathway emerged as a novel therapeutic target for neuropathic pain2. While the antinociceptive effects of fingolimod have already been demonstrated in neuropathic pain3 models no study have investigated this effect in an MS model. So our aim was to characterize the fingolimod effect in a relapsing-remitting (RR) experimental autoimmune encephalomyelitis (EAE) mouse model with neuropathic pain symptoms4.
Methods: We evaluated the effects of an early curative fingolimod treatment (0.5mg/kg/day) on clinical scores, motor performances as well as paw sensitivity to mechanical and thermal (cold and heat) stimuli.
Results: We showed in treated EAE mice that fingolimod: significantly ameliorates the clinical symptoms, totally reverses the mechanical allodynia and partially improves cold allodynia and thermal heat hypersensitivity.
Conclusion: We then showed for the first time that fingolimod can not only improves the EAE clinical scores but also ameliorates nociceptive symptoms. Given that neuropathic pain is lacking of efficient treatment, fingolimod could represent a first-line therapy in this subtype of MS patients.
Perspectives: We have to decipher if the fingolimod effects on nociceptive symptoms is dependent or independent to its effect on EAE score. In such a way we will evaluate the effect of sub chronic, late curative or local (i.e. intrathecal) treatment on both symptoms, as well as, characterize the cellular changes associated with these clinical improvements.
1 Foley et al., Pain 2014
2 Welch et al., Biochem. Pharmacol. 2012
3 Janes et al., Journal of Biological Chemistry 2014,
4 Khan et al., Pharmacology, Biochemistry and Behavior 2014
Disclosure:
Démosthènes: nothing to disclose.
Daulhac-Terrail: nothing to disclose.
Eschalier: nothing to disclose.
Bégou: nothing to disclose.
Abstract: EP1464
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 13 Experimental models
Background and aims: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that causes different debilitating symptoms including neuropathic pain in many patients (47%)1. Among current treatments, fingolimod, a non-selective sphingosine-1-phosphate (S1P) receptor modulator showed promising effect on MS outcome. In the same time, the S1P pathway emerged as a novel therapeutic target for neuropathic pain2. While the antinociceptive effects of fingolimod have already been demonstrated in neuropathic pain3 models no study have investigated this effect in an MS model. So our aim was to characterize the fingolimod effect in a relapsing-remitting (RR) experimental autoimmune encephalomyelitis (EAE) mouse model with neuropathic pain symptoms4.
Methods: We evaluated the effects of an early curative fingolimod treatment (0.5mg/kg/day) on clinical scores, motor performances as well as paw sensitivity to mechanical and thermal (cold and heat) stimuli.
Results: We showed in treated EAE mice that fingolimod: significantly ameliorates the clinical symptoms, totally reverses the mechanical allodynia and partially improves cold allodynia and thermal heat hypersensitivity.
Conclusion: We then showed for the first time that fingolimod can not only improves the EAE clinical scores but also ameliorates nociceptive symptoms. Given that neuropathic pain is lacking of efficient treatment, fingolimod could represent a first-line therapy in this subtype of MS patients.
Perspectives: We have to decipher if the fingolimod effects on nociceptive symptoms is dependent or independent to its effect on EAE score. In such a way we will evaluate the effect of sub chronic, late curative or local (i.e. intrathecal) treatment on both symptoms, as well as, characterize the cellular changes associated with these clinical improvements.
1 Foley et al., Pain 2014
2 Welch et al., Biochem. Pharmacol. 2012
3 Janes et al., Journal of Biological Chemistry 2014,
4 Khan et al., Pharmacology, Biochemistry and Behavior 2014
Disclosure:
Démosthènes: nothing to disclose.
Daulhac-Terrail: nothing to disclose.
Eschalier: nothing to disclose.
Bégou: nothing to disclose.