Background & Aims

Persistent and chronic pain are significant contributors to diminished quality of life following acute musculoskeletal injury. This study identified predictors of chronic pain in patients with blunt chest trauma resulting in multiple closed rib fractures. Rib fractures are commonly recognized as a significant source of acute pain following injury; however, they also have a high rate of transition to chronic pain (1). The objective was to identify critical biomarkers to predict susceptibility/resilience to the development of chronic pain using blunt chest trauma with multiple rib fractures as a model. This project consists of three major aims: 1) identify prognostic clinical factors that predict a predisposition for susceptibility and/or resilience to pain chronification; 2) identify functional brain imaging biomarkers associated with the development of chronic pain; and 3) identify nociceptive genetic patterns at the time of injury that are predictive of pain chronification.

Methods

These are interim results of a prospective observational study in adults recruited from a level 1 trauma center following acute musculoskeletal trauma consisting of blunt chest injuries associated with multiple closed rib fractures. Data collected near the time of injury included demographics, medical history, clinically relevant assessments including patient-reported measures, quantitative sensory testing, functional brain imaging, and analysis of the genetic background. Participants were then contacted at 3 and 6 months after the injury to assess persistent chronic chest wall pain and conduct psychological assessments. The primary endpoint was defined as the number of patients with chronic pain at 6 months after injury and associated pain biomarkers from four sources: 1) patient-reported measures, 2) quantitative sensory testing, 3) functional brain imaging, and 4) genetic background.

Results

The preliminary results were obtained from 40 participants with multiple rib fractures. Successful pain management, as indicated by self-reported lowest pain scores within 24 hours at baseline was predictive of pain at both the 3- and 6-month timepoints (ps < 0.01). Additionally, participants who indicated their pain interfered with 'relationships with others' were more likely to have greater pain at 3 months after the injury (p < 0.01). At the 3-month post-injury timepoint, statistically significant associations with severe pain phenotype were observed for variants in the intronic portion of RBFOX1 (rs756411, p < 0.001) and SKA3 (rs913206, p < 0.001), and the exonic portion of the SLC52A3 (rs3746804, p < 0.001) gene. At the 6-month post-injury timepoint, statistically significant associations of variants with the severe pain phenotype were observed for variants in the intronic part of UGT1A (rs2602381, p < 0.001) and SGF29 (rs9928136, p < 0.001) genes.

Conclusions

Initial analyses suggest that managing acute pain will lead to better long-term pain outcomes. Further, preliminary results indicate associations between pain at 3 months after injury and gene variants involved in regulating hypersensitivity in nerves (RBFOX1), pathological conditions associated with central nervous system function (SLC52A3), cognitive function and affective impairment on quality of life (SKA3). At 6 months after the injury, pain was associated with the presence of gene variants related to analgesic metabolism (UGT1A) and aging processes in many cell types (SGF29). Further analyses are needed to delineate potential markers and specific pathways that may serve as targets for therapeutic intervention.

References

1. Baker E, Xyrichis A, Norton C, Hopkins P, Lee G. The long-term outcomes and health-related quality of life of patients following blunt thoracic injury: a narrative literature review. Scand J Trauma Resusc Emerg Med 2018;26(1): 67.

Presenting Author

Jennifer E. Nyland

Poster Authors

Jennifer Nyland

PhD

Penn State College of Medicine

Lead Author

E-mail

Piotr Janicki

MD

Penn State College of Medicine, Milton S. Hershey Medical Center

Lead Author

E-mail

Sanjib Adhikary

MBBS

Penn State College of Medicine, Milton S. Hershey Medical Center

Lead Author

E-mail

Andrea Hobkirk

PhD

Penn State College of Medicine

Lead Author

E-mail

David Giampetro

MD

Penn State College of Medicine, Milton S. Hershey Medical Center

Lead Author

E-mail

Sangam Kanekar

MD

Penn State College of Medicine, Milton S. Hershey Medical Center

Lead Author

E-mail

Prasanna Karunanayaka

PhD

Penn State College of Medicine

Lead Author

E-mail

Ryan Staszak

MD

Penn State College of Medicine, Milton S. Hershey Medical Center

Lead Author

E-mail

Shouhao Zhou

PhD

Penn State College of Medicine

Lead Author

E-mail

Aimee Cauffman

RN

Penn State College of Medicine, Milton S. Hershey Medical Center

Lead Author

E-mail

Ann Sipe

MS

Penn State College of Medicine

Lead Author

E-mail

Corinne Augusto

Penn State College of Medicine

Lead Author

E-mail

Sara Mills-Huffnagle

Penn State College of Medicine

Lead Author

E-mail

Topics

  • Models: Transition to Chronic Pain