Supraspinal Processing of Sensory Aspects of Pain

Study Overview
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Brief Summary
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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
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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.

Official Title
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Supraspinal Processing of Sensory Aspects of Pain

Conditions
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Fibromyalgia, Migraine in Children, Complex Regional Pain Syndromes, Musculoskeletal Pain, Functional Abdominal Pain Syndrome

Intervention / Treatment
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* Other: Multisensory Task
* Other: Graphesthesia
* Other: Divided attention


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Controls<br>Healthy controls with no history of chronic pain. | Other: Multisensory Task<br>* Reversing checkerboard, tones, and finger opposition.<br>Other: Graphesthesia<br>* Trace numbers on skin.<br>Other: Divided attention<br>* Divide attention between two noxious stimuli.<br>|
| Experimental: Headache and Migraine<br>Individuals who have migraine with headaches. | Other: Multisensory Task<br>* Reversing checkerboard, tones, and finger opposition.<br>Other: Graphesthesia<br>* Trace numbers on skin.<br>Other: Divided attention<br>* Divide attention between two noxious stimuli.<br>|
| Experimental: Functional Abdominal Pain Disorder (FAPD)<br>Individuals who have functional abdominal pain disorder. | Other: Multisensory Task<br>* Reversing checkerboard, tones, and finger opposition.<br>Other: Graphesthesia<br>* Trace numbers on skin.<br>Other: Divided attention<br>* Divide attention between two noxious stimuli.<br>|
| Experimental: Localized and Diffuse/Widespread Musculoskeletal Pain (MSK)<br>Individuals with chronic musculoskeletal pain. | Other: Multisensory Task<br>* Reversing checkerboard, tones, and finger opposition.<br>Other: Graphesthesia<br>* Trace numbers on skin.<br>Other: Divided attention<br>* Divide attention between two noxious stimuli.<br>|
| Experimental: Complex Regional Pain Syndrome (CRPS)<br>Individuals with complex regional pain syndrome. | Other: Multisensory Task<br>* Reversing checkerboard, tones, and finger opposition.<br>Other: Graphesthesia<br>* Trace numbers on skin.<br>Other: Divided attention<br>* Divide attention between two noxious stimuli.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FMRI: BOLD resting connectivity of the amygdala | BOLD resting connectivity of the amygdala | Baseline | 
| Resting Cerebral Blood Flow (CBF) | CBF derived from resting arterial spin labeled MRI | Baseline | 
| FMRI: Multisensory task activity | BOLD activation during multisensory task | Baseline | 
| FMRI: Spatial task activity | BOLD activation during spatial summation and divided attention | Baseline | 
| FMRI: BOLD resting connectivity of the posterior parietal cortex | BOLD resting connectivity of the posterior parietal cortex | Baseline | 
| FMRI: Graphesthesia Activation | BOLD activation during graphesthesia task | Baseline | 
| Pain Ratings | 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. | Baseline | 
| Pain Ratings | 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. | 1 Year Followup | 
| Spatial Distribution of Pain | Body map assessment of location of pain | Baseline | 
| Spatial Distribution of Pain | Body map assessment of location of pain | 1 Year Followup | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic pain