Preclinical investigations utilizing murine experimental auto-immune
encephalomyelitis (EAE), as well as clinical observations in patients with
multiple sclerosis (MS), may suggest alteration of endogenous
opioid systems in MS. In this study we used the
opioid antagonist naltrexone (NTX) to invoke a continuous (High Dose NTX, HDN) or intermittent (Low Dose NTX, LDN)
opioid receptor blockade in order to elucidate the role of native
opioid peptides in EAE. A mouse model of
myelin oligodendrocyte glycoprotein (MOG)-induced EAE was employed in conjunction with daily treatment of LDN (0.1 mg/kg, NTX), HDN (10 mg/kg NTX), or vehicle (saline). No differences in neurological status (incidence, severity, disease index), or neuropathological assessment (activated astrocytes,
demyelination, neuronal injury), were noted between MOG-induced mice receiving HDN or vehicle. Over 33% of the MOG-treated animals receiving LDN did not exhibit behavioral signs of disease, and the severity and disease index of the LDN-treated mice were markedly reduced from cohorts injected with vehicle. Although all LDN animals demonstrated neuropathological signs of EAE, LDN-treated mice without behavioral signs of disease had markedly lower levels of activated astrocytes and
demyelination than LDN- or vehicle-treated animals with disease. These results imply that endogenous
opioids, evoked by treatment with LDN and acting in the rebound period from
drug exposure, are inhibitory to the onset and progression of EAE, and suggest that clinical studies of LDN are merited in MS and possibly in other autoimmune disorders.