Neuroinflammation and Oxidative Stress in Neuropathic Pain: Mechanistic Targets for Nutraceutical-Based Interventions

Neuropathic pain is a chronic, difficult-to-treat condition arising from injury or disease of the somatosensory nervous system. Current pharmacological treatments provide limited relief for many patients and are often associated with adverse effects, highlighting the need for complementary mechanism-based strategies. Neuroinflammation and oxidative stress are pivotal and interdependent drivers of neuropathic pain, promoting glial activation, cytokine release, mitochondrial dysfunction, redox imbalance, ion channel sensitization, and peripheral and central sensitization. Nutraceuticals and dietary bioactive compounds have gained attention because of their pleiotropic actions, i.e., multiple pharmacological activities, on inflammatory, oxidative, metabolic, mitochondrial, and neuroimmune pathways. This review summarizes the mechanistic roles of neuroinflammation and oxidative stress in neuropathic pain and discusses evidence supporting nutraceutical-based interventions, including polyphenols, terpenoids, alkaloids, fatty acids and lipid-derived compounds, antioxidant nutraceuticals, vitamins, and micronutrients. Preclinical studies indicate that these compounds can attenuate pain-related behaviors by modulating redox-sensitive inflammatory signaling, glial reactivity, mitochondrial function, nociceptive ion channels, and endogenous antioxidant defenses. Although clinical evidence remains limited, selected compounds, including alpha-lipoic acid, palmitoylethanolamide, omega-3 fatty acids, B-complex vitamins, vitamin D, and capsaicin, show translational promise. Future studies should prioritize standardized formulations, bioavailability, dosing, safety, mechanistic biomarkers, and robust randomized trials to clarify their clinical role as complementary, multi-target strategies for neuropathic pain management.