Clinical Assessment of Pain Processes in Pediatric Patients With Chronic Musculoskeletal Pain (MSK)

Musculoskeletal (MSK) pain is one of the most common types of pain among children and adolescents. Recurring episodes of MSK pain during childhood does not only impact physical and psychological aspects of daily life but may predispose children and adolescents to experience recurrent pain-related illnesses while in adulthood. Thus, effective early life pain management is critical in avoiding a cascade of ill adaptive behaviors. Close to 16,000 children are seen in the clinics of the Shriners Hospital for Children - Canada each year. In the clinic, questionnaires are the standardized clinical way to access the patient's history on pain experience and their perception of it. However, clinicians currently lack the tools to objectively examine pain processes. The ultimate goal of this project is to investigate pain assessment techniques that could be used to phenotype pediatric MSK pain by their endogenous central pain modulation efficacy to provide a more personalized approach to pain management.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Pain

Detailed Description

Enabling better pain management in children with musculoskeletal (MSK) pathologies by improving assessment techniques is a cornerstone of this research program.

This research project will elucidate the regulation of specific physiological mechanisms related to pain in children reporting presence of chronic MSK pain. As molecular events of pathophysiological processes are quantifiable, the investigators will test for associations between the expression of pain-related molecular markers in blood and the patient's experience of pain assessed with semi-objective sensory testing. The identification of specific alterations in the nociceptive process will provide a deeper understanding of a patient's pain perception alongside self-report or observers' report subjective measurements. Pain experience variability may originate in the lack of rigor in the clinical pain assessment tools. A personalized mechanism-based approach may be the key to better identify a patient's pain outcome and how this assessment could lead to personalized pain management. By testing temporal summation (TS), conditioned pain modulation (CPM), electroencephalography (EEG) patterns and balance in relation to biomarkers, the investigators will be able to determine the phenotype of the patients who presents higher risk of central sensitization related to increased hyperactivity and decreased endogenous inhibition. The ultimate goal is to use this information to offer the highest quality of pain control in children with MSK conditions.

• Study Type: Observational
• Enrollment (Anticipated): 518

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H4A0A9
      • Shriners Hospital for Children-Canada

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited from outpatient clinics at the Shriners Hospitals for Children - Canada. Healthy participants will be recruited through word of mouth and recruitment advertisements in local magazines and social media. In collaboration with the public relations department of the hospital, previously-edited videos demonstrating the rationale and safety of the QST procedures mixed with interviews of past subjects will also be shared to promote the project and minimize potential concerns regarding our clinical assessment of pain.

Description

Inclusion Criteria:

• Aged between 10 and 18 years old
• Report of MSK pain lasting 3 months or longer, including orthopaedic diagnoses such as those involving the spine, knees, hips, ankles, shoulders.
• Ability to adequately understand and respond to outcome measures
• Female or male
• Any ethnic background

Exclusion Criteria:

• Inability of the child to speak English or French
• Pain due to an acute trauma occurring in the last 3 months (e.g. fracture)
• Diagnosed with developmental delay that would interfere with understanding questions being asked (autism, mental retardation)
• Children with major chronic medical conditions (ASA status III or higher)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Chronic MSK Pain; Participants who have chronic musculoskeletal pain.The pain profile of the patient will be assessed, including biological sample analysis (blood), quantitative sensory testing, electroencephalogram (EEG), and psychological state via the completion of questionnaires by the patient.
Healthy Control; Participants who do not have chronic musculoskeletal pain.The pain profile of the patient will be assessed, including biological sample analysis (blood), quantitative sensory testing, electroencephalogram (EEG), insole assessment (40 healthy control participants), and psychological state via the completion of questionnaires by the patient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mechanical detection threshold (grams) as measured with von Frey filaments		Completed during study visit (5 minutes).
Dynamic mechanical allodynia (numerical pain intensity using Faces Pain Scale -Revised scores 0-10) as measured with a standardized brush (Somedic SENSELab - Brush-05)		Completed during study visit (5 minutes).
Vibration detection threshold (Hertz) as measured with a Rydel-Seiffer graded tuning fork (64 Hz)		Completed during study visit (5 minutes).
Temporal mechanical summation (numerical pain intensity using Faces Pain Scale -Revised scores 0-10) as measured with the Neuropen (Owen Mumford) with disposable Neurotips		Completed during study visit (15 minutes).
Pain pressure threshold (Newtons) as measured with an algometer.		Completed during study visit (5 minutes).
Conditioned pain modulation (CPM) efficiency, a physiological parameter calculated as the percentage difference between the average pain intensity (0-10) reported during a thermode (heat) test before and after a cold water submersion bath test.		Completed during study visit (20 minutes).
Electroencephalography (EEG) (μV) as measured with a 24-electrode wireless EEG headset (DSI-24, Wearable Sensing)		Completed during study visit (5 minutes).
Biochemical assessment and genomic analysis of blood sample (10ml), drawn by research nurse.	A molecular assessment of monoamines involved in the dopaminergic and adrenergic pain (pathways related to the endogenous pain inhibitory system (dopamine, serotonin, epinephrine,norepinephrine) will be performed. Genomics analyses will be done to analyze specific single-nucleotide polymorphisms (SNPs). This process involves amplification of specific DNA fragments by polymerase chain reaction (PCR) followed by analysis on an optical plate for specific genetic polymorphisms, to identify which patients carry such polymorphisms.	The blood samples will be analyzed within 1 year of the study visit.
Insole assessment (N; N/cm2; mm/s; mm) as measured with Moticon© sensor insoles	Forty participants who agree to participate in the insole assessment will be asked to stand on sensory insoles for a duration of fifteen seconds to measure the forces, pressures and center of pressure in their feet. The measurement data obtained using the Moticon© insoles will be aggregated for analysis of plantar pressure distribution, which will be performed using the Moticon© software.	Completed during study visit (5 minutes).
Total score on Neuropathic Pain Questionnaire (DN4) (0-10) assessing the probability of neuropathic pain (score greater than 4 indicates neuropathic pain).	2 domains (Interview (0-7) and Examination (0-3) of the Patient) Completed by MSK chronic pain participants.	Completed during study visit (5 minutes).
Total Score of the Functional Disability Inquiry (0-60). Higher scores indicate greater activity limitations during the past 2 weeks.	Completed by MSK chronic pain participants.	Completed during study visit (5 minutes).
Total Subscale Score of the Adolescent Pediatric Pain Tool (APPT), which evaluates the intensity, location, and quality (including affective, evaluative, sensory, and temporal) dimensions of pain.	The APPT provides five subscale scores: 1) the number of pain sites (alternatively, the number of pain segments) as a measure of pain location from marks on a body outline; 2) a pain intensity score measured by a 10-centimeter line known as the Word Graphic Rating Scale (WGRS) and anchored by words no pain, little, medium, large, worst possible pain; 3) the number of pain quality descriptors, which yields percent scores for the sensory, affective, evaluative subscales; 4) the number of temporal descriptors, which yields a percent temporal subscale; and (5) the percent of total pain quality and temporal descriptors as a total subscale. Completed by MSK chronic pain participants.	Completed during study visit (5 minutes).
Global Score of the Pittsburgh Sleep Quality Index (0-21). Higher scores indicate a worse sleep quality (>5 indicates "poor sleeper").	Completed by all participants	Completed during study visit (5 minutes).
Total Anxiety Score and Total Internalizing Scale on the Revised Children Anxiety and Depression Scale (RCADS) (0-47) (t-score of 65 = borderline clinical threshold, t-score 70 = above clinical threshold)	The RCADS is intended to assess children's report of symptoms corresponding to selected DSM-IV anxiety disorders and depression. . Scale yields Total Anxiety Score (5 anxiety subscales: separation anxiety disorder, social phobia, generalized anxiety disorder, panic disorder, obsessive compulsive disorder), which gives an overall index of anxiety levels, and Total Internalizing Scale (sum of all 6 subscales, including major depression subscale), which provides an estimate of the total level of internalising symptoms. Completed by all participants.	Completed during study visit (5 minutes).
Total Score of the Pain Catastrophizing Scale (0-52). Higher scores indicate higher levels of pain-related anxiety.	Completed by all participants.	Completed during study visit (5 minutes).
Score of Trait Anxiety of the State-Trait Anxiety Scale (20-60). Higher scores indicate greater trait anxiety.	Completed by healthy control participant only.	Completed during study visit (5 minutes).

Collaborators and Investigators

• Sponsor: Shriners Hospitals for Children
• Investigators: Principal Investigator: Catherine Ferland, PhD, Shriners Hospitals for Children,Canada

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2018
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): November 1, 2022

Study Registration Dates

• First Submitted: March 9, 2020
• First Submitted That Met QC Criteria: March 11, 2020
• First Posted (Actual): March 13, 2020

Study Record Updates

• Last Update Posted (Actual): May 4, 2022
• Last Update Submitted That Met QC Criteria: May 3, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Quantitative Sensory Testing; Pain Management; Conditioned Pain Modulation; Chronic Musculoskeletal Pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Chronic Pain; Musculoskeletal Pain
• Other Study ID Numbers: A09-M17-17B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No