Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article


Doctor of Philosophy


Health and Rehabilitation Sciences

Collaborative Specialization

Musculoskeletal Health Research


Walton, David M.


The findings presented in this dissertation are part of the bigger SYMBIOME project which aims to use the biopsychosocial model of pain to develop a prognostic clinical phenotype for people that experience musculoskeletal (MSK) trauma. Chapter 2 presents an exploratory analysis to assess the relationships between genetic polymorphisms and pain severity and interference. Early childhood trauma was also explored as a moderator between genetic polymorphisms and pain outcomes. For pain severity, major allele carriers (A/A and G/A) of FKBP5 rs9394314 reported significantly higher scores than minor allele carriers (G/G). Further, major allele carriers who had at least one adverse childhood experience (ACE) reported significantly higher scores than minor allele carriers with at least one ACE. For pain interference, minor allele carriers (G/G) of CNR2 rs2501431 scored significantly higher than major allele carriers (A/A and G/A). Chapter 3 presents a cluster analysis that combines genotypes of FKBP5 rs9394314 and CNR2 rs2501431 to explore meaningful relationships with pain and trauma-related distress. ACE was also explored as a moderator of these relationships. Three clusters were identified where the second cluster characterized by major allele carriers of rs9394314 and minor allele carriers of rs2501431 reported significantly higher pain-related functional interference scores. Participants in the second cluster with at least one ACE reported higher pain interference and traumatic distress scores compared to the third cluster, while participants in the first cluster with at least one ACE reported higher pain severity compared to the first cluster. Chapter 4 presents genomic structural equation models (SEM) that explore the relationships of genotypes with trauma-related distress using the traumatic injuries distress scale (TIDS), ACE, and recovery outcomes. The results demonstrate a relationship between TIDS and recovery outcomes, and an indirect relationship between FKBP5 rs9394314 and recovery outcomes exist which is mediated by TIDS. Major allele carriers of FKBP5 rs9394314 reported higher TIDS scores, which was also demonstrated for participants that had at least one ACE. Major allele carriers that scored higher on the TIDS were predicted to be in the none-recovered category. These results support the notion that gene-x-environment interactions may play an important role in pain and recovery.

Summary for Lay Audience

Pain is a complicated experience that involves different processes within the body. When one or more of these processes fail to respond, pain can become a long-term problem that begins to affect quality of life. People struggling with chronic pain start to suffer in other areas of life including work, mental and physical health, financial burdens, and relationships. Understanding and treating pain can be difficult because of how unique it is to each person. To improve our understanding of pain and how to treat it effectively, we must consider the biological, psychological, and societal factors involved. The purpose of this project is to explore how genetic variations and environmental factors together play a role in a person’s pain and recovery outcomes by collecting blood samples and using questionnaires from a sample of people that suffered an acute traumatic injury. After one year of tracking our participants, some people developed chronic pain while others fully recovered. By comparing the differences in genetic variants and psychological responses between these people, we have a better understanding of why some people recover while others develop chronic pain. Factors such as early childhood trauma may also contribute to how your genes develop, causing differences in how you respond to a traumatic injury later in life and your ability to recover. Studying different genetic variants along with environmental influences may provide more insight on the types of new treatments that need to be developed to help treat people with pain before their pain becomes a chronic issue.