Potential roles of metabolomic alterations in neuropathic pain: Evidence from In Vivo to clinical studies

Neuropathic pain is a chronic condition often associated with damage to the somatosensory nervous system. The exact mechanistic understanding of neuropathic pain remains elusive. Metabolomics, an analytical approach used to assess metabolic alterations in various diseases, is a promising technique that can offer mechanistic insights into neuropathic pain. It may lead to the identification of novel therapeutic targets and biomarkers. Evidence from animal studies indicates that alterations in multiple metabolic pathways, including those involving amino acids, fatty acids, glycolysis intermediates, Krebs cycle metabolites, and eicosanoids, have been observed in models of neuropathic pain. Changes in several metabolites, including phosphatidylcholine, arachidonic acid derivatives, and amino acid levels, have also been found in models of neuropathic pain. These alterations have been associated with mitochondrial dysfunction, impaired maintenance of the myelin sheath, and increased pain signaling. In addition, clinical studies have demonstrated dysregulation of glutamate, choline, phospholipid, and glucose metabolism in patients with neuropathic pain. These metabolic disturbances contribute to neuronal hyperexcitability and persistent pain. Interestingly, modulation of specific metabolic pathways has been shown to alleviate neuropathic pain, as evidenced by both in vivo and clinical studies. Therefore, this comprehensive review aims to summarize and discuss the metabolomic alterations associated with neuropathic pain.