Nanozymes in neuropathic pain: strategies bridging oxidative stress, mitochondrial repair, and neuroimmune modulation for targeted therapy.

Neuropathic pain is one of the most debilitating neurological conditions, significantly challenging to manage due to the complex interplay of oxidative stress, neuroinflammation, and mitochondrial dysfunction in its pathogenesis. Nanozyme (nanomaterials with enzyme-like activity) technology offers a promising strategy to tackle these multifaceted mechanisms. These nanozymes can scavenge reactive oxygen species (ROS), modulate inflammatory pathways, and reverse mitochondrial dysfunction, providing notable neuroprotection and pain relief for affected individuals. Additionally, nanozymes exhibit targeted delivery to the injury sites by using mechanisms such as lysosome-mediated endocytosis (e.g., SOD&Fe3O4@ZIF-8 nanozymes) and mannose receptor-mediated cellular uptake (e.g., mSPIONs nanozymes). Given the limitations of current treatment options, we underscore the advantages of nanozymes, including their multifunctional capabilities and potential to enhance therapeutic outcomes in pain management. This review focuses on the underlying mechanisms of neuropathic pain, particularly emphasizing the role of oxidative stress and its impact on disease progression. We examine the applications of nanozymes for treating neuropathic pain, highlighting their potential to scavenge ROS, relieve mitochondrial dysfunction, modulate neuroinflammatory pathways, and repair blood-spinal cord barrier integrity. Furthermore, this paper provides an overview of the current landscape of nanozyme research in neuropathic pain and future directions for their clinical translation in pain management, emphasizing their potential role in improving therapeutic outcomes.