Can biomarkers differentiate pain and no pain subgroups of nonverbal children with cerebral palsy? A preliminary investigation based on noninvasive saliva sampling.

OBJECTIVE: Assessing and treating pain in nonverbal children with developmental disabilities are a clinical challenge. Current assessment approaches rely on clinical impression and behavioral rating scales completed by proxy report. Given the growing health relevance of the salivary metabolome, we undertook a translational-oriented feasibility study using proton nuclear magnetic resonance (NMR) spectroscopy and neuropeptide/cytokine/hormone detection to compare a set of salivary biomarkers relevant to nociception. DESIGN: Within-group observational design. SETTING: Tertiary pediatric rehabilitation hospital. SUBJECTS: Ten nonverbal pediatric patients with cerebral palsy with and without pain. METHODS: Unstimulated (passively collected) saliva was collected using oral swabs followed by perchloric acid extraction and analyzed on a Bruker Avance 700 MHz NMR spectrometer. We also measured salivary levels of several cytokines, chemokines, hormones, and neuropeptides. RESULTS: Partial least squares discriminant analysis showed separation of those children with/without pain for a number of different biomarkers. The majority of the salivary metabolite, neuropeptide, cytokine, and hormone levels were higher in children with pain vs no pain. CONCLUSIONS: The ease of collection and noninvasive manner in which the samples were collected and analyzed support the possibility of the regular predictive use of this novel biomarker-monitoring method in clinical practice.

Changes in the NMR metabolic profile of human microglial cells exposed to lipopolysaccharide or morphine.

Microglial cells play a major role in host defense of the central nervous system. Once activated, several functional properties are up-regulated including migration, phagocytosis, and secretion of inflammatory mediators such as cytokines and chemokines. Little, if anything, is known about the metabolic changes that occur during the activation process. High-resolution (1)H nuclear magnetic resonance spectra obtained from perchloric acid extracts of human microglial cell cultures exposed to lipopolysaccharide (LPS) or morphine were used to both identify and quantify the metabolites. We found that human microglia exposed to LPS had increased concentrations of glutamate and lactate, whereas the cells exposed to morphine had decreased concentrations in creatinine, taurine, and thymine. Glutamate and creatinine were the key metabolites differentiating between the two stimuli. These results are discussed in terms of activation and differences in the inflammatory response of human microglial cells to LPS and morphine.