Complex Regional Pain Syndrome (CRPS) is a severe and complex chronic pain condition in children. Many psychosocial factors impact its development and recovery. CRPS has a strong central component, which is reflected by structural and functional changes in the brain. However, the interaction between these cerebral changes and trajectory of recovery has been seldom investigated to date. Furthermore, interactions between cerebral changes and psychosocial factors, which might affect trajectory of recovery, are unknown. The aim of this study is to identify the psychosocial factors and cerebral changes that predict the trajectory of recovery from CRPS.

Children between the ages of 10 and 17 years will be enrolled with one of their parents or legal guardians for this study. Three populations will be recruited: patients with CRPS undergoing treatment at the Functional Independence Restoration Program (FIRST), patients with CRPS undergoing treatment at the Pain Management Center and matching healthy controls. Participants will undergo three sessions: the first session will be scheduled immediately before or as soon as possible at the beginning of the patients' treatment; the second session will take place at the end of the patients' treatment; the last session will be scheduled six months post-treatment. The timing of the sessions of the healthy participants will follow a schedule similar to the FIRST patients. Each session will last approximately three hours and include acquisition of psychosocial, psychophysical, and brain imaging data in the child participants, as well as acquisition of psychosocial data in the parent participants.

This is a basic science investigation of potential psychosocial, sensory, and brain markers predicting trajectory of short-term and long-term recovery in pediatric CRPS following both inpatient and outpatient treatment.

The usual inpatient treatment lasts on average three weeks and includes physical, occupational, and recreational therapy, as well as psychotherapy, while patients keep their regular pharmacological treatment. The usual outpatient treatment lasts on average several months and includes physical therapy and psychotherapy, in addition to pharmacotherapy. For both inpatients and outpatients, the primary anti-neuropathic pharmacotherapy typically includes gabapentin, pregabalin, or amitriptyline, or, less frequently, duloxetine. It is important to note that this study is not designed to investigate the efficacy of treatment per se, instead it aims to predict trajectory during the course of treatment as usual. This study is primarily mechanistic and does not include any intervention or modification of treatments. Therefore, patients, who are scheduled for regular inpatient or outpatient treatment of CRPS, are free to refuse to enroll without any consequences for the scheduled treatment.

The investigated markers will be assessed in patients undergoing inpatient or outpatient treatments. To define potentially relevant markers, measurements in patients will be compared to the same measurements in healthy children. For this purpose, participants will undergo a testing session just before the beginning of their treatment or as close as possible from the beginning of their treatment.

To establish the influence of potential markers on short-term recovery, patients will undergo an additional session upon completion of their treatment. To investigate the effect of the previously defined markers on long-term recovery, patients will complete a third session at six months after treatment. For comparison purposes, healthy control children will undergo sessions following the same schedule as the patients. To assess the association between symptoms of CRPS in children and social environment, at least one parent of each enrolled child will be asked to complete three sessions following the same schedule as their child.

Each testing session will include self-reported questionnaires for the children and their parents and a brain imaging session for the children.

Inclusion Criteria:

All Children:

• Age between 10 and 17 years old
• Fluent in English

Inpatients:

• Diagnosis of CRPS
• Former unsuccessful treatment for CRPS
• Scheduled for or beginning the usual inpatient treatment for CRPS at the FIRST clinic at CCHMC.

Outpatients:

• Diagnosis of CRPS
• Scheduled for or beginning the usual outpatient treatment for CRPS at the pain management clinic

Healthy children:

- No diagnosis of chronic pain.

Parents:

• Fluent in English
• Child participating in the study

Exclusion Criteria:

All child participants:

• Weight/size incompatible with MRI scanner
• Identification of brain, neurologic, or severe psychiatric abnormalities beyond those normally associated with chronic pain.
• Documented developmental delays or impairment
• Any MRI contra-indication, including
• Braces, stents, clips, pace-maker or other metal implants affecting the safety of the participants in the scanner and/or the quality of the images
• pregnancy
• claustrophobia

Participants to this study may be part of one of the following groups: children diagnosed with CRPS undergoing inpatient treatment at the FIRST clinic (CCHMC), children diagnosed with CRPS underdoing outpatient treatment at the pain management clinic (CCHMC or comparable outpatient programs), or healthy children. The investigator's groups will be matched as well as possible for BMI, sex, and age. In addition, one parent will be recruited with each child.