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The Long Term Suppression of Experimental Autoimmune Encephalomyelitis by the Opioid Growth Factor and Low Dose Naltrexone

Title
The Long Term Suppression of Experimental Autoimmune Encephalomyelitis by the Opioid Growth Factor and Low Dose Naltrexone
Publication Type
Journal Article
Research Type
Animal
Reported as
Date
April 01, 2011
Authors
Zagon, IS; Rahn, KA
Institution
Penn State University
Link
Abstract

Endogenous opioid peptides play a critical role in determining the progression of experimental autoimmune encephalomyelitis (EAE), a model for Multiple Sclerosis (MS). Treatment of animals with the enkephalin Opioid Growth Factor ([Met5]-enkephalin) or low dose naltrexone (LDN) to alter opioid-receptor interactions attenuates disease symptoms up to 20 days after induction. This study examined the behavior and neuropathology of mice with myelin oligodendrocyte glycoprotein (MOG)-induced EAE after 8 weeks of treatment with OGF or LDN. The incidence of disease for MOG+OGF and MOG+LDN animals was reduced by more than 30% relative to MOG+Vehicle controls, and disease severity in these mice was decreased by 37% and 26%, respectively. Mice in the MOG+OGF and MOG+LDN groups had notably more (42% and 23%, respectively) remissions (defined as a 2 more days of a behavior score of 0) than animals in the MOG+Vehicle group. The number of reactive astrocytes (GFAP), number of spinal cord quadrants that expressed demyelination (absence of Luxol fast blue staining), and number of damaged neurons (SMI-32) were markedly reduced in mice receiving OGF or LDN. These results indicate that OGF or LDN have a long term suppressive effect on the progression of EAE, providing novel therapeutic modalities for the treatment of MS.