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

Abstract

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.

Catestatin and vasostatin concentrations in healthy dogs

“…Saliva sampling is preferable in humans because it is less invasive than blood sampling [54, 55]. In dogs, however, stress behaviors during saliva and blood sampling have not previously been evaluated and prolonged sampling time could induce stress [56, 57].…”

“…In humans, saliva sampling is preferable to blood sampling for monitoring stress because the technique is noninvasive [54, 55] and humans can be informed of the procedure and deliver saliva samples by voluntary spitting into a container. To obtain spontaneous saliva samples in dogs, however, collection swabs must be intraorally placed.…”

Pathophysiology of chronic pain in cerebral palsy: implications for pharmacological treatment and research

“…Recent investigation into pain biomarkers will assist in objective pain monitoring for intervention studies. Salivary metabolites, neuropeptides, cytokines, and hormone levels are higher in children with pain versus those in no pain . While salivary cortisol has been shown to be more useful as a marker for acute rather than chronic pain in CP, hair cortisol shows promise for chronic pain .…”

“…Salivary metabolites, neuropeptides, cytokines, and hormone levels are higher in children with pain versus those in no pain. 30 While salivary cortisol has been shown to be more useful as a marker for acute rather than chronic pain in CP, 25,31 hair cortisol shows promise for chronic pain. 32 Functional magnetic resonance imaging has been found increasingly useful in pain research.…”

Pain in Intellectually Disabled Children: Towards Evidence-Based Pharmacotherapy?

“…Another area of pain assessment is the analysis of salivary cortisol levels and other biomarkers [ 34 ]. New, simple techniques have been developed to determine cortisol levels with the use of a smartphone app [ 35 ].…”