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

Abstract

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, l-Lysine 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.

• Authors: Qi Zhang, Qingchun Li, Siying Liu, Hangping Zheng, Lijin Ji, Na Yi, Xiaoming Zhu, Wanwan Sun, Xiaoxia Liu, Shuo Zhang, Yiming Li, Qian Xiong, Bin Lu
• Journal: Diabetes research and clinical practice (Diabetes Res Clin Pract) Vol. 176 Pg. 108790 (Jun 2021) ISSN: 1872-8227 [Electronic] Ireland
• PMID: 33812900 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier B.V.

Chemical References

• Amino Acids
• Streptozocin

Topics

• Amino Acids (analysis, metabolism, physiology)
• Animals
• Brain (metabolism)
• Brain Chemistry (physiology)
• Diabetes Mellitus, Experimental (chemically induced, complications, metabolism, physiopathology)
• Diabetic Neuropathies (etiology, metabolism, physiopathology)
• Hyperalgesia (complications, metabolism, physiopathology)
• Male
• Metabolomics
• Neuralgia (etiology, metabolism, pathology)
• Rats
• Rats, Sprague-Dawley
• Streptozocin