Dysregulated Resolution of Inflammation After Respiratory Viral Infections: Molecular Pathways Linking Neuroinflammation to Post-Viral Neuropathic Pain-A Narrative Review.

Publication date: Nov 25, 2025

Post-viral neuroinflammatory syndromes, particularly those occurring after SARS-CoV-2 infection, have received increasing attention due to their complex and persistent neurological manifestations. The aim of this narrative review is to integrate current evidence on the molecular and cellular mechanisms underlying chronic neuroinflammation following viral infections, with a focus on dysregulated innate immune responses, macrophage-microglia interactions, oxidative-mitochondrial stress, and impaired inflammation resolution pathways. Our synthesis shows that prolonged activation of macrophages and glial cells promotes the continuous release of pro-inflammatory mediators, while defective phagocytosis and inadequate clearance of cellular debris maintain an inflammatory microenvironment. Mitochondrial dysfunction further amplifies immune activation by stimulating metabolic stress and reactive oxygen species production. In parallel, deficiencies in mediators specialized in inflammation resolution impede the transition from inflammation to resolution, allowing neuroimmune imbalance and nociceptive sensitization to persist long after virus clearance. Key conclusions indicate that these interconnected mechanisms collectively contribute to the long-term neurological symptoms observed in post-viral states, including cognitive impairment, neuropathic pain, and fatigue. Emerging therapeutic strategies targeting cytokine signaling, microglial reactivity, mitochondrial function, and resolution pathways are promising, but remain insufficiently validated in clinical practice. Overall, evidence suggests that post-viral neuroinflammation results from the convergence of sustained immune activation and failure of endogenous resolution mechanisms, highlighting the need for further mechanistic studies and targeted interventions.

Semantics

Original Article