Enkephalin Therapy Improves Relapsing-Remitting Multiple Sclerosis

Patel, Chirag; Zagon, Ian S.; Thomas, Garrett; McLaughlin, Patricia J.

doi:10.5772/intechopen.91010

Cited by 2 publications

(2 citation statements)

References 80 publications

(136 reference statements)

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“…Naltrexone is a general opioid receptor antagonist used to treat alcohol and opioid addiction at 50 mg (Raknes & Småbrekke, 2017; Toljan & Vrooman, 2018). In contrast, LDN at a dosage of <5 mg/day has been shown to have beneficial effects on autoimmune pathologies such as Crohn's, fibromyalgia, and rheumatoid arthritis (Lie et al., 2018; Patel et al., 2020; Toljan & Vrooman, 2018; Younger et al., 2014; Zagon & McLaughlin, 2017, 2018). In EAE, LDN has been shown to reduce clinical symptomatology through the modulation of endogenous opioid signaling (Ludwig et al., 2017, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…In EAE, LDN has been shown to reduce clinical symptomatology through the modulation of endogenous opioid signaling (Ludwig et al., 2017, 2018). The treatment of mice with 0.1 mg/kg LDN daily resulted in the restoration of serum levels of [Met] 5 ‐enkephalin (termed opioid growth factor (OGF)), which are reduced in both MS and EAE (Ludwig et al., 2017; Patel, Zagon, et al., 2020). In addition to restoring OGF levels in serum, LDN altered expression of both pro‐ (IFNγ) and anti‐inflammatory (IL‐10) cytokines in mice with EAE (Ludwig et al., 2018).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Timing of treatment with an endogenous opioid alters immune response and spinal cord pathology in female mice with experimental autoimmune encephalomyelitis

Patel

Zagon

Pearce-Clawson

et al. 2021

J of Neuroscience Research

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Multiple sclerosis (MS) is a progressive disease of the central nervous system (CNS) that primarily affects women during the second or third decade of life. The mechanism is hypothesized to involve unregulated peripheral inflammation resulting in bloodbrain barrier damage, and eventual axonal damage and demyelination. Based on this understanding, the animal model of MS, experimental autoimmune encephalomyelitis (EAE), often is utilized to study lymphocyte activation. Therapeutic paradigms of exogenous opioid growth factor (OGF) or low-dose naltrexone (LDN) treatment can modulate EAE, but little is reported regarding OGF or LDN effects on peripheral inflammation, microglia activation, and/or macrophage proliferation. Moreover, little is known about differential responses to LDN or OGF relative to the duration and timing of treatment. Utilizing a female mouse model of EAE, two treatment regimens were established to investigate differences between prophylactic treatment and traditional therapy initiated at the time of disease presentation. Prophylactic OGF or LDN treatment delayed the onset of behavior, suppressed neutrophil replication, and curtailed lymphocyte proliferation which ultimately improved behavioral outcome. Traditional therapy with OGF or LDN reversed behavioral deficits, restored OGF and IL-17 serum levels, and inhibited microglial activation within 8 days. Reduced serum OGF levels in untreated EAE mice correlated with increased microglia activation within lumbar spinal cords. Both treatment regimens of OGF or LDN reduced activated microglia, whereas only prophylactic treatment prevented CNS macrophage aggregation. These data demonstrate that the timing of LDN or OGF treatment initiation alters outcomes and can prevent or reverse behavioral deficits, cytokine activation, and spinal cord pathology.

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