Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article


Doctor of Philosophy


Health and Rehabilitation Sciences


Walton, David M.


This dissertation presents the initial findings of the SYMBIOME project; which attempts to combine the objective and subjective aspects of musculoskeletal pain to develop a prognostic clinical phenotype. Chapter 2 presents a moderator analysis of functional outcomes (pain interference and pain severity). Psychosocial moderators can affect the relationship between biomarkers and pain. For pain severity, TNF-α, TGF-β1, and CRP were moderated by employment status, pre-existing psychopathology, and sex. For pain interference, IL-1β, cortisol, TGF-β1, CRP, and IL-6 were moderated by pre-existing pain, peri-traumatic fear, region of injury, and peri-traumatic stress. Chapter 3 presents a latent growth curve analysis in determining the recovery trajectories of acute non-catastrophic musculoskeletal pain in the context of pain interference and severity over the course of 12 months. For pain interference, 3 distinct trajectories emerged: rapid recovery, delayed recovery, or minimal/no recovery. Pain severity favored a 2-trajectory model with rapid recovery or minimal/no recovery. Classification of recovery group depended on both baseline symptoms and relative rate of symptom decline. Recovery outcomes appeared to stabilize after a period of 3 months. Chapter 4 presents latent class analysis and growth mixture modeling as applied to a panel of 8 biomarkers (TNF-α, IL-1β, IL-6, CRP, IL-10, cortisol, BDNF, and TGF-β1). These markers may have the potential to discriminate between functional recovery outcomes. Using these markers, 3 meaningful groups or classes were identified. These groups could be adequately defined by using only 3 of the 8 markers (IL-1β, BDNF, and TGF-β1) where classes were organized by low concentration of markers in serum, average concentration, or high concentration of BDNF and TGF-β1. Those with high concentration of BDNF/TGF-β1 were more likely to score higher on self-report measures of pain and disability in their 6-month outcomes. These results support the claim that physiological factors are tied to pain through more than simple bivariate relationships. The context of the musculoskeletal trauma, both personal and social, can affect the behavior of biological systems.

Summary for Lay Audience

Pain is a complex process that occurs in our body. It involves psychology, genetics, and a combination of the immune, nervous and endocrine systems. Short-term pain is important because it helps us survive. However, when something goes wrong in one of those systems, it can become a long-term problem. As pain goes on, it begins to affect the quality of life. For the 20% of Canadians who struggle with chronic pain, everything begins to suffer including health, finances, relationships, and work. Because pain is such a personal experience, it is very difficult to understand and treat.

The SYMBIOME project stands for the SYstematic Merging of BIOlogy, Mental Health, and Environment. The purpose of this project is to understand how pain develops over time. After a traumatic accident or injury, people are invited into this year-long study. By using questionnaires and collecting tissue samples, we have monitored their recovery. After one year, some people fully recover while others develop chronic pain. When we compare the mental and physical changes that occur between these people, it helps us understand how pain becomes chronic. Your work status, education level, mental health, and physical injuries all contribute to how your body deals with trauma. These factors can influence your healing responses in a way that either increases or decreases your levels of inflammation and stress in the short-term. In the long-term, it may also affect your ability to recover as people tend to recover in 1 of 3 ways. Some people recover quickly and are functioning normally by 6 months. Some are delayed in their recovery but still reach normal function. And some people still struggle with pain and disability even after 12 months. Analyzing various groups of blood proteins may also shed some light on who tends to recover and who does not. With this information, it will be possible to develop new treatments that can help people who suffer from chronic pain. It may also help us treat pain in unique ways before it has a chance to become a chronic problem.