Leaky Blood–Brain Barrier and Chronic Pain: The Neuroinflammatory Link

Chronic pain represents a significant clinical challenge and is frequently associated with neuroinflammatory processes. The blood–brain barrier plays a central role in protecting the central nervous system by regulating the passage of molecules and immune cells from the periphery. Emerging evidence indicates that in chronic pain conditions, BBB integrity can be compromised, facilitating the infiltration of pro-inflammatory cytokines, immune cells, and neurotoxic mediators into the CNS. These changes contribute to microglial and astrocyte activation, enhancing central sensitization and the persistence of pain. Animal models and clinical studies suggest that mechanisms including tight junction disruption, oxidative stress, and matrix metalloproteinase release underlie this increased permeability. Understanding BBB modulation in chronic pain not only clarifies disease pathophysiology but also highlights potential therapeutic strategies aimed at preserving or restoring barrier integrity.