Pilot Study Evaluating Neuro-Imaging Correlates of Epigenetic Finding in Prediction of Chronic Postsurgical Pain

This pilot research study is being performed to learn more about pain and look at how pain changes brain chemistry and function. The research team would like to learn new information to better control chronic pain after surgery. This information collected in this research will be used to plan possible future visits. Participants in this study are being asked to participate because they are scheduled for an upcoming surgery. The research team would like to observe them before and after their surgery.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Post-surgical Pain

Detailed Description

This study is a pilot feasibility study in 30 healthy, preoperative children and young adults undergoing major surgery with high risk for chronic post-surgical pain (CPSP) to characterize the brain metabolite status of the Anterior cingulate cortices (ACC) and insula in pre-surgical adolescents and to understand the relationship between metabolite levels and CPSP. The investigators will also examine whether neurochemical tone in these regions is related to resting state functional connectivity with other brain regions. Correlations between differentially methylated CpG sites in genes enriching gamma aminobutyric acid (GABA) and Dopamine-DARPP-32 pathways and Glu/GABA levels in insula/ACC will be analyzed.

• Study Type: Observational
• Enrollment (Actual): 13

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing chest surgery (thoracotomy, thoracoscopy, Nuss procedure, pectus surgery, mastectomy), spine surgery, amputation, hernia repair or hip/knee replacement in the hospital.

Description

Inclusion Criteria:

1. Male or female aged ≥ 8 yrs of age
2. English speaking;
3. Healthy (Defined as American Society of Anesthesiologists Physical Status 1 or 2)
4. Ability to provide assent/consent/parent permission.
5. Scheduled to undergo chest surgery (thoracotomy, thoracoscopy, Nuss procedure, pectus surgery, mastectomy), spine surgery, amputation, hernia repair or hip/knee replacement.

Exclusion Criteria:

1. History of chronic pain conditions including migraines
2. Use of opioids chronically or for major surgery within the 6 months prior to enrollment
3. Severe obesity (BMI>35 kg/m2)
4. Taking no more than two concomitant medications known to induce or inhibit CYP2D6 activity, including paroxetine, fluoxetine, cimetidine, and duloxetine or other medications used to treat attention deficit hyperactivity disorder (medications containing amphetamine or methylphenidate).
5. Use of hormonal contraceptives
6. Use of medications that may alter pain sensitivity (e.g. gabapentin,/pregabalin amitryptiline/other antidepressants, clonidine).
7. Active or history of renal/liver problems or congenital cardiac disease
8. Diagnosed developmental delay
9. Pregnant or lactating females
10. Any skin condition that prevents cuff application
11. History of seizures
12. Claustrophobia
13. Metallic implants/orthodontics/braces or other MRI exclusion (MRI safety screening will be conducted prior to enrollment and prior to each MRI scan)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chronic post-surgical pain; Unabbreviated scale title "Chronic post-surgical pain scores"	Pain scores over prior 2 weeks reported 2-6 months after surgery; minimum value = 0, maximum value = 10; higher score means more severe pain	2-6 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evoked pressure pain measures; Unabbreviated scale title "Evoked pressure pain measures"	Average of 3 measurements taken using a hand-held algometer; minimum value = 0, maximum value = None; higher measurement means better pain tolerance	1-2 weeks after surgery
Resting state connectivity	Pressure cuff measurements while undergoing MRI scan	1 - 8 weeks before surgery
Correlation of DNAm of specified gene regions with outcomes	Differential DNAm measured by array/sequencing	1-8 weeks before surgery or day of surgery

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Investigators: Principal Investigator: Vidya Chidambaran, MD, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2020
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: December 18, 2020
• First Submitted That Met QC Criteria: December 18, 2020
• First Posted (Actual): December 23, 2020

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative
• Other Study ID Numbers: 2020-0277

Drug and device information, study documents

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