Can Biomarkers Differentiate Pain and No Pain Subgroups of Nonverbal Children with Cerebral Palsy? A Preliminary Investigation Based on Noninvasive Saliva Sampling

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 700MHz 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.