Decreased amino acids in the brain might contribute to the progression of diabetic neuropathic pain

Aims: The pathophysiological alteration of diabetic neuropathic pain (DNP) in brain is unclear. Here we aimed to explore the metabolomic characteristics of brain in rats over the progression of DNP through metabolomic analysis. Methods: Adult rats were randomly divided into control group and DNP group. Body weight, blood glucose and behavioral assessment of neuropathic pain were measured every week after streptozotocin (STZ) injection. Finally, the brains of 2 rats from control group and 6 rats from DNP group were removed every 4 weeks after STZ injection for metabolomics analysis. Results: After 4 weeks of STZ-injection, the rats with diabetes developed DNP, which was characterized as mechanical allodynia and thermal nociception. As for metabolomic analysis, differentially expressed metabolites (DE metabolites) showed a dynamic alteration over the development of DNP and affected several KEGG pathways associated with amino acid metabolism. Furthermore, the expression of L-Threonine, L-Methionine, D-Proline, LLysine and N-Acetyl-L-alanine were significantly decreased at all time points of DNP group. The amino acids which were precursor of analgesic neurotransmitters were downregulated over the progression of DNP, including L-tryptophan, L-histidine and L-tyrosine. Conclusions: The impairment of amino acid metabolism in brain might contribute to the progression of DNP through decreasing analgesic neurotransmitters. (C) 2021 Published by Elsevier B.V.