title: 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.
authors.affiliation: Student Brigade, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Changhai Hospital, Shanghai, 200433, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Changhai Hospital, Shanghai, 200433, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, Changhai Hospital, Shanghai, 200433, China.
authors.forename: Youshui
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Student Brigade, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Songyan
authors.initials: S
authors.lastname: Gao
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Nephrology, Changhai Hospital, Shanghai, 200433, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005620:Freund's Adjuvant / Q000633:toxicity*; D006930:Hyperalgesia / Q000139:chemically induced*; D013058:Mass Spectrometry; D055432:Metabolomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014556:Urine
chemical_list: D015415:Biomarkers; D005620:Freund's Adjuvant
keywords: UHPLC-Q-TOF/MS; complete Freund's adjuvant; hyperalgesia; metabolomics; urine