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Oxidative stress contributes to persistent pain and central sensitization in a repeated PGE2-induced hyperalgesic priming model

Year: 2026

Type: article

Abstract: Chronic pain is a global health concern that impairs physical and psychological well-being. Recently, nociplastic pain, characterized by the absence of overt inflammation or nerve injury, has gained attention as a distinct chronic pain condition. Central sensitization is considered a primary mechanism underlying nociplastic pain and the persistence of chronic pain states. Emerging evidence suggests that oxidative stress contributes to central sensitization, through increased neuronal excitability and glial activation; however, its role in nociplastic pain remains unclear. In this study, we investigated the involvement of oxidative stress in a prostaglandin E2 (PGE2)-induced hyperalgesic priming mouse model with features resembling nociplastic pain. Additionally, we examined the effects of modulating oxidative stress on pain progression using a silicon (Si)-based antioxidant agent. Repeated PGE2 administration induced mechanical allodynia and increased circulating reactive oxygen metabolites (d-ROMs), effects that were attenuated in mice treated with the Si-based agent. In the spinal dorsal horn, neuronal activity and astrocyte activation increased in the chronic pain model but not in mice treated with the Si-based agent. These findings support an association between systemic oxidative stress and spinal sensitization in this repeated PGE2-induced hyperalgesic priming model and provide insight into mechanisms underlying persistent pain that may share features with nociplastic pain.

Source: Scientific Reports

DOI: 10.1038/s41598-026-76376-1