Neuropathic pain (NP) is a complex chronic pain syndrome often secondary to conditions such as diabetic peripheral neuropathy and postherpetic neuralgia. It not only severely compromises patients’ quality of life but also imposes a heavy burden on healthcare systems. Recent studies indicate that plasma lipoproteins play a significant role in its pathophysiology, with functions extending beyond lipid transport to include extensive involvement in inflammatory regulation, oxidative stress, and maintenance of neural function. This review aims to systematically elucidate the intricate relationship between NP and lipoproteins, analyze its pathophysiological mechanisms, and transcend conventional perspectives by conducting in-depth analyses of the specific mechanisms of action of high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) in pain. Consequently, it explores potential therapeutic strategies based on lipoprotein metabolism. This review demonstrates that distinct lipoprotein types exert critical roles in the initiation and maintenance of NP through differentiated mechanisms involving regulation of neuroinflammation, oxidative stress, and ion channel function. These findings not only expand our understanding of pain mechanisms but also provide theoretical foundations for developing novel therapeutic strategies targeting lipoprotein metabolism. Future clinical research is essential to advance these insights into safe and effective personalized analgesic approaches.
Hao et al. (Mon,) studied this question.