The related mechanism of complete Freund's adjuvant‐induced chronic inflammation pain based on metabolomics analysis

Abstract

Chronic inflammation pain is a debilitating disease, and its mechanism still remains poorly understood. This study attempted to illuminate the metabolic mechanism of chronic inflammation pain induced by complete Freund’s adjuvant (CFA) injection, especially at spinal level. The chronic inflammation pain model was established by CFA administration. Behavioral testing including mechanical allodynia and thermal hyperalgesia was performed. Meanwhile, a liquid chromatography–mass spectrometry‐based metabolomics approach was applied to analyze potential metabolic biomarkers. The orthogonal partial least squares discrimination analysis mode was employed for determining metabolic changes, and a western blot was performed to detect the protein expression change. The results showed that 27 metabolites showed obviously abnormal expression and seven metabolic pathways were significantly enriched, comprising aminoacyl‐tRNA biosynthesis, arginine and proline metabolism, histidine metabolism, purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glutathione metabolism, and phenylalanine metabolism. Meanwhile, the results showed that the expression of arginase I and nitric oxide levels were elevated in the CFA group compared with the control group, while the argininosuccinate synthetase and argininosuccinatelyase proteins were not significantly different between the groups. These findings demonstrate that metabolic changes of the spinal cord may be implicated in neurotransmitter release and pain conductivity following CFA administration.

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“…CFA-induced arthritis group showed increasing in serum CRP concentration comparing with normal group this result is similar to Geyer et al (2020), who observe that CRP levels increase in reaction to inflammation, and the autoimmune illness also produces significant amounts of inflammation in addition to other signs like swollen and aching joints. Zhang et al (2021) approved that CFA injection induce chronic inflammation and pain. Decreasing of TAC serum level indicated in CFA-induced arthritis group this result confirmed by the results of ArezooMoradi et al (2022), who discover that oxidative stress, a state in which the pool of reactive oxygen species, rises over time either by their increased production or because TAC is the main protection against oxidative stress, there is an inverse relationship between TAC and the illness.…”

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