An NMR-based metabolic profiling study of inflammatory pain using the rat FCA model

The objective measurement of chronic pain in pre-clinical animal models and in the clinical arena is problematic. The multifactorial nature of pain can adversely affect the accuracy with which it can be quantitatively assessed. This is due to diverse aetiology, environmental factors and psychological status which can significantly affect the measurement of pain in animal models and presentation in the clinic. In pre-clinical studies, the objectivity of pain measurement is affected by variability in behavioural phenotype and the lack of verbal description, while clinical pain is subject to variance by a considerable placebo effect, thought to be related to merely being in a clinical setting. Therefore, it would be advantageous to identify a biological marker which is sensitive to pain pathology and modulated by an efficacious analgesic/anti-inflammatory agent. The present study highlights several metabolites present in urine that are modulated from basal levels by pain and inflammation induced following hindpaw injection of Freund's Complete Adjuvant. Nuclear magnetic resonance (NMR) analysis of urine and multivariate statistical data analysis (MVDA) were used to examine in detail the modulation of small molecule candidate biomarkers or surrogates. Several molecules were shown by NMR to be modulated by FCA injection including carboxylates, acetylated metabolites, choline metabolites, tricarboxylic acid cycle intermediates, creatine and creatinine, taurine, N-methylnicotinamide and its metabolites and several unassigned peaks.