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In addition to the antagonist effect on mu-opioid and other opioid receptors, naltrexone simultaneously has an antagonist effect on non-opioid receptors (Toll-like receptor 4 or TLR4) that are found on macrophages such as microglia
It is via the non-opioid antagonist path that LDN is thought to exert its anti-inflammatory effects
Once activated, microglia produce inflammatory and excitatory factors that can cause sickness behaviors such as pain sensitivity, fatigue, cognitive disruption, sleep disorders, mood disorders, and general malaise
The neuroprotective action appears to result when microglia activation in the brain and spinal cord is inhibited
By suppressing microglia activation, naloxone reduces the production of reactive oxygen species and other potentially neuroexcitatory and neurotoxic chemicals
suppressed TNF-alpha, IL-6, MCP-1, and other inflammatory agents in peripheral macrophages
individuals with greater ESR at baseline experienced a greater drop in pain when taking LDN
LDN has been reported to reduce not only self-reported pain in that condition but also objective markers of inflammation and disease severity
Naltrexone has also shown some promise in improving disease severity in multiple sclerosis