Supraspinal Processing of Sensory Aspects of Pain

Not Applicable

Recruiting

• Conditions: Complex Regional Pain Syndromes; Musculoskeletal Pain; Functional Abdominal Pain Syndrome; Migraine in Children; Fibromyalgia
• Interventions: Other: Multisensory Task; Other: Graphesthesia; Other: Divided attention

• Registration Number: NCT05814497
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

Brief Summary

The goal of this basic science study is to learn about the brain mechanisms of chronic pain across different chronic pain syndromes in pediatric patients. The main questions it aims to answer are:

* Are there shared and distinct brain systems engaged by different forms of pediatric chronic pain?

* What are predictors of recovery from chronic pain?

* What brain systems are associated with the spread of pain?

For this study participants will undergo:

* Functional Magnetic Resonance Imaging (fMRI)

* Quantitative Sensory Testing

* Psychological Assessments

Detailed Description

Chronic pain affects approximately 20% of both adults and children in the US and is a source of substantial disability and health care costs. Chronic pain can be challenging to diagnose due to the presence of poorly understood symptoms. When diagnosed, current pharmacologic treatments for pain are remarkably ineffective, while effective non-pharmacologic treatments remain under-utilized. These shortcomings in the diagnosis and treatment of pain arise from tremendous gaps in our knowledge about the basic central nervous system systems that process nociceptive information and instantiate an experience of pain. These gaps are further amplified in the case of pediatric chronic pain due to a lack of basic/translational research. The team of basic scientists and clinician scientists is uniquely positioned to perform human pediatric studies integrating functional neuroimaging with quantitative sensory testing and psychological assessments to delineate brain systems engaged during chronic pain. The study will examine four distinct chronic pain syndromes: migraine, complex regional pain syndrome, functional abdominal pain, and musculoskeletal pain. The study seeks to 1) Identify shared and distinct brain systems engaged by different forms of pediatric chronic pain, 2) Determine if predictors of recovery differ across different chronic pain conditions, 3) Delineate brain systems associated with the spread of pain. To accomplish these aims, the study will recruit 400 patients with chronic pain and 100 healthy participants (age range 10-17). The study will follow all participants longitudinally for 1 year after initiation of treatment to assess the degree of recovery and spread of pain. This basic science investigation will provide a critical foundation of basic knowledge for future clinical trials of diagnostic markers for different forms of chronic pain and for the development of new treatments for chronic pain.

Study Timeline

• Study First Submitted: 2023-02-10
• Study First Submitted QC: 2023-04-12
• Study First Posted: 2023-04-18
• Study Start: 2023-05-01
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-03
• Last Update Posted: 2025-01-06
• Primary Completion: 2027-06-30
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

• Patients will need a diagnosis of a chronic pain derived congruent with ICD-11 criteria related to headache (migraine, daily headache), abdominal (FAPD), localized MSK (single limb/joint, low back or chest pain), diffuse MSK (widespread MSK pain), or CRPS
• If on medications, they need to be on stable doses of prescribed pain and/or psychiatric medications for 4 weeks before the baseline study visit.
• Male or female, age 10 -17 (inclusive)
• English speaking, able to complete interviews and questionnaires in English

Exclusion Criteria

• Weight/size incompatible with MRI scanner
• Orthodontic braces, metallic or electronic implants, or other metal objects in the body which obscure or interfere with the MRI, or pose a risk from heating, movement, or malfunction in the MRI environment
• Claustrophobia
• Youth who are pregnant
• Any comorbid rheumatic disease, diagnosis of epilepsy, other neurological diseases, or medical condition (e.g. diabetes, cancer, IBD)
• Present psychiatric disease as defined by DSM IV (e.g. psychosis, bipolar disorder, major depression, generalized anxiety disorder), alcohol or drug dependence, or documented developmental delays or impairments (e.g., autism, cerebral palsy, ADHD, or mental retardation) that, in the opinion of the investigator, would interfere with adherence to study requirements or safe participation in the study
• Skin conditions or past skin damage on the arms or legs in or near sites of sensory testing
• Outside the age range (9 years old or younger; 18 years or older) at the time of consent
• History of > 1 month opioid treatment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Healthy Controls	Graphesthesia	Healthy controls with no history of chronic pain.
Headache and Migraine	Graphesthesia	Individuals who have migraine with headaches.
Headache and Migraine	Divided attention	Individuals who have migraine with headaches.
Functional Abdominal Pain Disorder (FAPD)	Graphesthesia	Individuals who have functional abdominal pain disorder.
Localized and Diffuse/Widespread Musculoskeletal Pain (MSK)	Graphesthesia	Individuals with chronic musculoskeletal pain.
Healthy Controls	Divided attention	Healthy controls with no history of chronic pain.
Functional Abdominal Pain Disorder (FAPD)	Divided attention	Individuals who have functional abdominal pain disorder.
Localized and Diffuse/Widespread Musculoskeletal Pain (MSK)	Multisensory Task	Individuals with chronic musculoskeletal pain.
Complex Regional Pain Syndrome (CRPS)	Graphesthesia	Individuals with complex regional pain syndrome.
Healthy Controls	Multisensory Task	Healthy controls with no history of chronic pain.
Headache and Migraine	Multisensory Task	Individuals who have migraine with headaches.
Localized and Diffuse/Widespread Musculoskeletal Pain (MSK)	Divided attention	Individuals with chronic musculoskeletal pain.
Complex Regional Pain Syndrome (CRPS)	Multisensory Task	Individuals with complex regional pain syndrome.
Functional Abdominal Pain Disorder (FAPD)	Multisensory Task	Individuals who have functional abdominal pain disorder.
Complex Regional Pain Syndrome (CRPS)	Divided attention	Individuals with complex regional pain syndrome.

Primary Outcome Measures

Name	Time	Method
Spatial Distribution of Pain	1 Year Followup	Body map assessment of location of pain
FMRI: BOLD resting connectivity of the amygdala	Baseline	BOLD resting connectivity of the amygdala
Resting Cerebral Blood Flow (CBF)	Baseline	CBF derived from resting arterial spin labeled MRI
FMRI: Multisensory task activity	Baseline	BOLD activation during multisensory task
FMRI: Spatial task activity	Baseline	BOLD activation during spatial summation and divided attention
FMRI: Graphesthesia Activation	Baseline	BOLD activation during graphesthesia task
Pain Ratings	1 Year Followup	Visual analog scale (VAS) ratings of pain intensity and pain unpleasantness. The VAS is a scale of 0-10, with higher scores indicating a worse outcome.
FMRI: BOLD resting connectivity of the posterior parietal cortex	Baseline	BOLD resting connectivity of the posterior parietal cortex

Trial Locations

Locations (1)

Cincinnati Children's Hospital; 🇺🇸 Cincinnati, Ohio, United States