Characterization of acupuncture on central amino acid metabolism based on targeted neurotransmitter analysis in mice with inflammatory pain

基于靶向神经递质分析的针灸对炎症性疼痛小鼠中枢氨基酸代谢的影响

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Abstract

OBJECTIVE: To investigate the effect of central amino acid metabolic profiles on acupuncture analgesia. METHODS: BALB/c mice were injected with Complete Freund's Adjuvant (CFA) and acupuncture was applied at Zusanli (ST36) for 7 d after modeling. Paw withdrawal thermal latency (PWTL) and paw withdrawal mechanical threshold (PWMT) were tested during the experiment. The level of prostaglandin E2 (PGE2) was measured by enzyme-linked immunosorbent assay (ELISA). Using liquid chromatography-mass spectrometry (LC-MS/MS) based on the multiple reaction monitoring (MRM)-targeted metabolomic approach, neurotransmitter in the brain and spinal cord as well as were detected, further tryptophan metabolites in spinal cord were detected, and the data was analyzed using multiquant software. RESULTS: Acupuncture significantly improved the PWTL and PWMT on the modeling side of CFA mice, and simultaneously, decreased the PGE2 level. Based on targeted neurotransmitter analysis, acupuncture increased the expression of phenylethylamine and decreased N-acetyl serotonin in the brain, while significantly up-regulated serotonin, and down-regulated the levels of homovanillic acid, 5-hydroxy-L-tryptophan and 3,4-Dihydroxyphenylethylene Glyco in the spinal cord. Further investigation targeted tryptophan metabolism found that acupuncture considerably decreased the content of tryptophan and L-kynurenine, but increased serotonin. CONCLUSIONS: This study aims to assess changes in central neurotransmitters of CFA mice treated with acupuncture, revealing that abnormalities in central neurotransmitter metabolism may be a potential biochemical basis for pain. More importantly, our preliminary study suggests the potential role of tryptophan and its metabolites in acupuncture analgesia, which may provide new insight and direction for the pain management interface of neurometabolism.

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