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Specifically, opioids modulate Toll-like receptor 4 (TLR4) signaling bidirectionally by activating TLR4 in the CNS to trigger NF-κB pathways and pro-inflammatory cytokine release (TNF-α, IL-1β, IL-6), leading to neuroinflammation, while inhibiting lipopolysaccharide (LPS)-induced TLR4 signaling in peripheral immune cells, resulting in immunosuppression [130]

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