Urinary metabolomics of complete Freund's adjuvant‐induced hyperalgesia in rats

Abstract

The aim of this study was to demonstrate the differences of metabolomics changes in a hyperalgesia model and find potent biomarkers of hyperalgesia. Seven rats were placed in metabolic cages. An emulsion containing 500 μg of Complete Freund's adjuvant (CFA) was used to induce hyperalgesia. Urine samples were collected prior to the injection of CFA and on post-injection days 1, 3 and 7. Ultraperformance liquid chromatography, coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS), was used for a quantitative analysis of urinary metabolic changes in the CFA-induced hyperalgesia model. Differences between the metabolic profiles of the rats in the four groups were analyzed using partial least squares discriminant analysis. Thirty-four potential urine metabolite biomarkers were identified, which changed in a trend similar to the pain threshold. These potential biomarkers were involved in 11 metabolic pathways, as follows: alanine, aspartate, and glutamate metabolism; ascorbate and aldarate metabolism; glycerolipid metabolism; glycerophospholipid metabolism; histidine metabolism; phenylalanine metabolism; sphingolipid metabolism; tryptophan metabolism; tyrosine metabolism; valine, leucine and isoleucine biosynthesis; and vitamin B6 metabolism. These results may improve our understanding of hyperalgesia and provide a basis for the clinical diagnosis of hyperalgesia.

Salivary metabolome indicates a shift in tyrosine metabolism in patients with burning mouth syndrome: a prospective case–control study

“…In a rat model of induced hyperalgesia, urine metabolomics identified a decrease of 7 metabolites of the tyrosine pathway (3-methoxy-4-hydroxyphenylethylene glycol, 2,5‐dihydroxybenzaldehyde, indole‐5,6‐quinone, N‐methyltyramine, homovanillic acid, dopaquinone, and l -dopa) during the first day of experiment, which returned to normal ranges in the following days. 54 In contrast to our results, tyrosine and phenylalanine levels were found to be increased in the cerebrospinal fluid of patients with complex regional pain syndrome 65 and tyramine levels were found to be elevated in plasma of patients with recurring headache attacks such as cluster headaches and migraine, 21 although not in patients with chronic tension-type headache. 20 Indeed, upon activated, trace amine-associated receptors (TAARs), which are enriched in subcortical centers of central nervous system implicated in modulation of pain, result in abnormal pain processing.…”

ASIC3-dependent metabolomics profiling of serum and urine in a mouse model of fibromyalgia

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“…Currently, data suggest that metabolic changes are relevant to many diseases, and metabolites obtained from accessible samples such as urine or plasma may serve as potential biomarkers for diagnosis of chronic inflammatory pain in the clinic (Liu et al, 2017a; Liu et al, 2017b). The spinal cord is the primary center of transmission signals.…”

“…Briefly, an emulsion containing 10 μl of CFA with saline (proportion 1:1) was injected into the left posterior plantar of mice ( n = 10). The control group received the same procedure with saline (Y. Liu et al, 2017b). Mice were allowed to acclimatize to the home cage and environment.…”