Abstract
Preclinical investigations utilizing murine experimental autoimmune 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1383-1392 |
| Number of pages | 10 |
| Journal | Experimental Biology and Medicine |
| Volume | 234 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2009 |
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All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
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Endogenous opioids regulate expression of experimental autoimmune encephalomyelitis : A new paradigm for the treatment of multiple sclerosis. / Zagon, Ian; Rahn, Kristen A.; Turel, Anthony P.; McLaughlin, Patricia.
In: Experimental Biology and Medicine, Vol. 234, No. 11, 01.11.2009, p. 1383-1392.Research output: Contribution to journal › Article
TY - JOUR
T1 - Endogenous opioids regulate expression of experimental autoimmune encephalomyelitis
T2 - A new paradigm for the treatment of multiple sclerosis
AU - Zagon, Ian
AU - Rahn, Kristen A.
AU - Turel, Anthony P.
AU - McLaughlin, Patricia
PY - 2009/11/1
Y1 - 2009/11/1
N2 - Preclinical investigations utilizing murine experimental autoimmune 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.
AB - Preclinical investigations utilizing murine experimental autoimmune 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.
UR - http://www.scopus.com/inward/record.url?scp=70350554076&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70350554076&partnerID=8YFLogxK
U2 - 10.3181/0906-RM-189
DO - 10.3181/0906-RM-189
M3 - Article
C2 - 19855075
AN - SCOPUS:70350554076
VL - 234
SP - 1383
EP - 1392
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
SN - 1535-3702
IS - 11
ER -