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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-8633 | Other Identifier | CCHMC IRB |
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This will be an open label, prospective study to determine the association between specific genotypes, epigenetics and behavioral factors, with the phenotypes, defined by pain perception, postoperative pain, analgesic and side effect responses to perioperative opioids, chronic postoperative pain and gene expression in adolescents following major spine surgery.
Safe and effective analgesia is an important unmet medical need in children. Despite efforts to promote non-pharmacologic interventions, drug treatment remains the standard of care for children experiencing severe pain following surgery. Inadequate pain relief after invasive surgery, and side effects from analgesics such as morphine occur frequently in up to 50% of children. A study of patient controlled analgesia (PCA) morphine use after spine surgery in adolescents observed a 45% incidence of postoperative nausea and vomiting and 7% incidence of respiratory depression. Presently, evidence-based dosing guidelines for opioid therapy have not been ascertained in the pediatric patient population, and remains a trial and error method. Despite aggressive pain management after spine surgery, findings showed that neither children's pain nor their analgesic use diminished significantly over time. As such, there is a critical knowledge gap in the medical literature that significantly impacts the pediatric pain management. Moreover, chronic postsurgical pain (CPSP, defined as pain attributable to the surgical procedure lasting for more than 2 months after surgery critically impacts 13-30% of children having surgery, and leads to chronic pain as adults imposing extraordinary annual costs on the health care system ($560-635 billion). It has been recently shown that pain unpleasantness predicts the transition from acute to moderate/severe persistent post-surgical pain, whereas anxiety sensitivity predicts the maintenance of moderate/severe post-surgical pain from 6 to 12 months after surgery. Spine fusion in adolescents is a particularly painful surgery with 15% incidence of pain even 5 years after surgery, and hence will serve as a good surgical model to evaluate the behavioral and genetic predictors of chronic postoperative pain. In recognition of this therapeutic challenge the investigators plan to evaluate the determinants of inter-individual differences in opioid analgesic responsiveness, adverse effects, pain perception and predictors of chronic postoperative pain in children.
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| Measure | Description | Time Frame |
|---|---|---|
| Numeric rating scale (NRS) pain scores | Data will be collected for 48 hours postoperatively | |
| Occurrences of respiratory depression | Respiratory rate (RR) <10 on POD 1 and 2 | Data will be collected for 48 hours postoperatively |
| Occurrences of post-operative nausea/vomiting (PONV) | Data will be collected for 48 hours postoperatively |
| Measure | Description | Time Frame |
|---|---|---|
| Amount of morphine (or equivalent) used by patient | Data will be collected for 48 hours postoperative | |
| Chronic pain postoperatively | Participants will complete questionnaires regarding pain since surgery was completed |
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Inclusion Criteria:
Exclusion Criteria:
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The investigators will recruit a total of 200 subjects over the study period to acquire the data necessary to derive a predictive model matching phenotype to genotype. They will be recruited from the population of children ages 10 to 18, inclusive, years scheduled for spinal surgical procedures.
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| Name | Affiliation | Role |
|---|---|---|
| Vidya Chidambaran, MD | Children's Hospital Medical Center, Cincinnati | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University Hospital | Stanford | California | 94305 | United States | ||
| Johns Hopkins Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39745877 | Derived | Einhorn LM, Monitto CL, Ganesh A, Duan Q, Lee J, Ramamurthi RJ, Barnett K, Ding L, Chidambaran V. Multi-Institutional Study of Multimodal Analgesia Practice, Pain Trajectories, and Recovery Trends After Spine Fusion for Idiopathic Scoliosis. Anesth Analg. 2025 Nov 1;141(5):1137-1148. doi: 10.1213/ANE.0000000000007351. Epub 2025 Jan 2. | |
| 34280572 |
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| ID | Term |
|---|---|
| D012600 | Scoliosis |
| D007738 | Kyphosis |
| D059350 | Chronic Pain |
| D010149 | Pain, Postoperative |
| ID | Term |
|---|---|
| D013121 | Spinal Curvatures |
| D013122 | Spinal Diseases |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
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Blood samples will be analyzed for a defined set of SNPs using PCR (TaqMan, ABI)/and Omni5M GWAS chip testing. DNA will be isolated from blood samples and also be used for pyrosequencing studies to obtain DNA methylation information for a specified set of genes or use of the MethylationEPIC array. The SNP sets were chosen using the adult studies cited in the Background and Significance section as evidence of potential importance. Given that the pain response in children and adolescents may involve a novel or different set of SNPs and additional SNPs of the above genes, the DNA samples gathered will be held for future analysis.
| 2 - 6 months postoperatively |
| Persistent pain postoperatively | Participants will complete questionnaires regarding pain since surgery was completed | 10 - 12 months postoperatively |
| Opioid addiction by history on follow-up | 1 year postoperatively |
| Baltimore |
| Maryland |
| 21205 |
| United States |
| University of Mississippi Medical Center | Jackson | Mississippi | 39216 | United States |
| Duke Children's Hospital | Durham | North Carolina | 27710 | United States |
| The Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Narayanasamy S, Yang F, Ding L, Geisler K, Glynn S, Ganesh A, Sathyamoorthy M, Garcia V, Sturm P, Chidambaran V. Pediatric Pain Screening Tool: A Simple 9-Item Questionnaire Predicts Functional and Chronic Postsurgical Pain Outcomes After Major Musculoskeletal Surgeries. J Pain. 2022 Jan;23(1):98-111. doi: 10.1016/j.jpain.2021.06.014. Epub 2021 Jul 17. |
| D010146 |
| Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |