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

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.

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.

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)