Projects

The King Lab is dedicated to understanding the biopsychosocial mechanisms contributing to pain. The lab uses several multidisciplinary techniques to evaluate various biological factors related to stress (inflammation) and altered pain processing (quantitative sensory testing, QST). The lab also measures key behavioral factors associated with pain, including sleep that we assess with self-report and actigraphy.

Markers predicting responses to pharmacological and non-pharmacological treatment in adolescents with migraine

This study is a collaborative effort between Behavioral Medicine and Clinical Psychology (BMCP) (Scott Powers, PhD, ABPP, FAHS and Robert Coghill, PhD) and the Headache Clinic (Andrew D. Hershey, MD, PhD, FAHS) at Cincinnati Children's. The study examines the brain and somatosensory mechanisms underlying amitriptyline, placebo and cognitive behavioral therapy in adolescents with migraines undergoing treatment. This study will obtain functional MRI and quantitative sensory testing (QST) data before and after intervention (8-week period). The grant will also explore if self-reported and objective sleep impacts treatment response. This study is funded by the National Institute of Neurological Disorders and Stroke (NINDS, R01NS101321) and the National Center for Complementary and Integrative Health (NCCIH, R01AT010171).

Sleep, pain modulation and inflammation in adolescents with Juvenile Fibromyalgia (JFM)

In collaboration with BMCP (Susmita Kashikar-Zuck, PhD) and Rheumatology (Tracy V. Ting, MD, MSc, RhMSUS and Grant Schulert MD, PhD), this study examines the biological mechanisms underlying JFM pain and prospectively identifies pathways in which modifiable behaviors (sleep) contribute to clinical symptoms and pain-related disability through changes in these mechanisms. Our objective is to determine if poor sleep and perturbations within the immune system can be observed and if they contribute to clinical symptoms in JFM. The fidelity of the immune system will be assessed with circulating cytokines, inflammatory gene expression and evoked-release of cytokines by a bacterial endotoxin, lipopolysaccharide (LPS).

Development and validation of a multimodal biological and psychological signature for MSK pain

In collaboration with other researchers at Stanford University and the University of Toronto / Hospital for Sick Children, the Signature of Pain Recovery IN Teens (SPRINT) study is evaluating the use of neuroimaging, immune, quantitative sensory and psychological markers in tandem with machine learning approaches to extract a prognostic signature from adolescents with MSK pain. This project will attempt to answer novel and important scientific questions regarding the identification and early validation of a signature to identify persistence vs. recovery of juvenile MSK pain, which would provide risk stratification in patients with chronic MSK. This study is funded by the National Institute of Neurological Disorders and Stroke (NINDS, R61NS11492).

Feasibility and Acceptability Study of Home PSG and Arousal Manipulation in Adolescents with Migraine

Intriguing emerging data, including ours, suggest alterations of the arousal system are a key mechanism linking poor sleep and pain in adolescents with chronic pain. This study will leverage an established mechanistic protocol (R01HL139652; Dr. de Zambotti) designed to reduce bedtime arousal in adolescents. Our near-term goal is to successfully compete for NIH / NINDS funding to examine the presence and impact of specific sleep-arousal processes on sleep and the perception of next-day pain in adolescents with migraine. More immediately, this RIP proposal would provide critical data on the feasibility of our design (At-home polysomnography (PSG) across two nights; arousal manipulation via 20 min virtual reality [VR] guided meditation + pace breathing) and collect preliminary data on several arousal markers hypothesized to underlie the sleep-pain relationship.

Altered pain processing in Adolescents with risk for Chronic Overlapping Pain Conditions (COPCs)

While localized primary pain conditions are prevalent in youth, a significant subset of these patients experience multiple pain conditions and meet the criteria for chronic overlapping pain conditions (COPCs). COPCs negatively impact daily functioning and quality of life in youth and carry a high risk for continued pain and disability into adulthood. The current proposal will determine whether disruptions in spatial (concurrent noxious stimuli across the body) and temporal (noxious stimuli presented over time) filtering of nociceptive processing, reflecting pain amplification (e.g., increased facilitation and/or reduced inhibition) contributes to COPCs. Several quantitative sensory testing (QST) methods are uniquely positioned to probe these disruptions. Our primary objective is to determine whether spatial and temporal filtering of nociceptive information differentiates youth with COPCs from those with localized pain and healthy controls and whether distinct profiles of disrupted nociceptive processing are associated with the transition of localized pain to COPCs. To accomplish this, the current study will leverage expertise and a vast clinical infrastructure at Cincinnati Children's, including the Headache Clinic (Andrew D. Hershey, MD, PhD, FAHS), Gastroenterology (Neha Santucci, MD, MBBS), Rheumatology (Tracy V. Ting, MD, MSc, RhMSUS) and Pain Management (Kenneth Goldschneider, MD, FAAP). We will also explore whether other factors, including sleep, influence the disrupted filtering and the transition to COPCs. The study received a bridge award from the National Institute of Neurological Disorders and Stroke (NINDS, R56NS126289-01).

Virtual Reality for Pain Management

In collaboration with Vanessa Olbrecht, MD (Nationwide Children’s Hospital) and Sara Williams, PhD (Stanford), we have been exploring the use and impact of virtual reality (VR) for the management of pain. Specifically, we have several projects looking at distraction and guided relaxation on postop pain in pediatric patients following surgery. Our current study, funded by National Center for Complementary and Integrative Health (NCCIH, 1R34AT011218), is refining our treatment protocol for the perioperative application of virtual reality and conducting a clinical trial using this treatment protocol in children and adolescents undergoing surgery.

A functional analysis pipeline for sleep and circadian rest/activity rhythms

Using funding from Cincinnati Children’s Pediatric Musculoskeletal & Rheumatology Innovation Core Center (PORTICO, P30AR076316), we are developing a computational pipeline using open-source R programming to generate sleep and physical activity outcomes. This functional analysis pipeline uses wrist-worn actigraphy data collected from sleep assessments in youth with widespread MSK pain. The actigraphy devices, which measure the frequency and vigor of movement throughout the day with accelerometry, are traditionally used for sleep monitoring. Since these devices are worn continuously across several days, circadian profiles can be calculated from the whole dataset rather than a specific phase (nighttime).