Each year, more than 5 million people are treated in US Emergency Departments (EDs) after """"""""minor"""""""" motor vehicle collision (MVC) and discharged to home. Persistent pain (most commonly neck pain) develops in 10- 20% of these individuals, with an economic impact of $29 billion per year in the United States alone. Contemporary knowledge regarding the pathogenesis of these common and costly disorders is summarized in biopsychosocial models of post-MVC pain pathogenesis. In recent years, the identification and detailed delineation of mechanisms by which psychological factors contribute to persistent pain development has substantially improved the biopsychosocial model. In contrast, biological factors in the biopsychosocial model remain relatively poorly defined, and are generally limited to estimates of crash severity or initial injury only. Interestingly, increasing evidence indicates that genetic characteristics influencing adrenergic system function may constitute important biological vulnerability factors for the development of posttraumatic pain, and thus may be important to incorporate into the biopsychosocial model. The immediate and ongoing adrenergic response is influenced by the function of important adrenergic system components, including enzymes and transporters that modulate synaptic catecholamine levels and receptors that orchestrate the cellular response. A growing literature documents the ability of these components to influence pain processing, and the investigators'pilot data support the hypothesis that genetic variation in these components affects vulnerability to develop immediate and persistent musculoskeletal pain after minor MVC. The goal of the proposed research, Genetic predictors of acute and chronic musculoskeletal pain after minor MVC, is to assess whether genotypes determining specific adrenergic system processes relevant to pain perception will, when combined with crash-related, psychological, and other factors, improve the prediction of immediate and persistent neck pain symptoms after minor MVC. Patients presenting for evaluation after minor MVC (n = 795) will be recruited in the ED and will receive initial ED evaluation including blood collection for genetic analyses. Patients will then be interviewed 1, 6, and 12 months after the MVC to assess pain outcomes. Pilot data demonstrate the ability of the study team to perform the proposed study and support the potential predictive value of the selected adrenergic system-related genetic factors. The proposed study provides an unprecedented opportunity to develop rich biopsychosocial prediction models of persistent post-MVC neck pain which integrate factors across multiple domains. These models will provide important new knowledge regarding both individual vulnerability characteristics and interactions between genetic and non-genetic factors during the development of post-MVC pain.

Public Health Relevance

The proposed study will provide new knowledge regarding both individual vulnerability characteristics and interactions between genetic and non-genetic factors during the development of persistent posttraumatic musculoskeletal pain. Understanding the etiology of musculoskeletal pain disorders is important to the public's health because these disorders are common, cause significant pain and suffering, and are very costly to society.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
3R01AR056328-03S1
Application #
8133183
Study Section
Special Emphasis Panel (ZRG1-CFS-E (01))
Program Officer
Panagis, James S
Project Start
2008-09-19
Project End
2012-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
3
Fiscal Year
2010
Total Cost
$107,577
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Dentistry
Type
Schools of Dentistry
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Madsen, Tracy E; McLean, Samuel; Zhai, Wanting et al. (2018) Gender Differences in Pain Experience and Treatment after Motor Vehicle Collisions: A Secondary Analysis of the CRASH Injury Study. Clin Ther 40:204-213.e2
Michopoulos, Vasiliki; Maples-Keller, Jessica; Roger, Elizabeth I et al. (2018) Nausea in the peri-traumatic period is associated with prospective risk for PTSD symptom development. Neuropsychopharmacology :
Feinberg, Rose K; Hu, JunMei; Weaver, Mark A et al. (2017) Stress-related psychological symptoms contribute to axial pain persistence after motor vehicle collision: path analysis results from a prospective longitudinal study. Pain 158:682-690
Beaudoin, Francesca L; Gutman, Roee; Merchant, Roland C et al. (2017) Persistent pain after motor vehicle collision: comparative effectiveness of opioids vs nonsteroidal antiinflammatory drugs prescribed from the emergency department-a propensity matched analysis. Pain 158:289-295
Linnstaedt, Sarah D; Walker, Margaret G; Riker, Kyle D et al. (2017) Genetic variant rs3750625 in the 3'UTR of ADRA2A affects stress-dependent acute pain severity after trauma and alters a microRNA-34a regulatory site. Pain 158:230-239
Auvergne, Lauriane; Bortsov, Andrey V; Ulirsch, Jacob C et al. (2016) Association of Epidemiologic Factors and Genetic Variants Influencing Hypothalamic-Pituitary-Adrenocortical Axis Function With Postconcussive Symptoms After Minor Motor Vehicle Collision. Psychosom Med 78:68-78
Meloto, Carolina B; Bortsov, Andrey V; Bair, Eric et al. (2016) Modification of COMT-dependent pain sensitivity by psychological stress and sex. Pain 157:858-67
Hu, JunMei; Bortsov, Andrey V; Ballina, Lauren et al. (2016) Chronic widespread pain after motor vehicle collision typically occurs through immediate development and nonrecovery: results of an emergency department-based cohort study. Pain 157:438-44
Linnstaedt, Sarah D; Bortsov, Andrey V; Soward, April C et al. (2016) CRHBP polymorphisms predict chronic pain development following motor vehicle collision. Pain 157:273-9
Qadri, Yawar J; Bortsov, Andrey V; Orrey, Danielle C et al. (2015) Genetic Polymorphisms in the Dopamine Receptor 2 Predict Acute Pain Severity After Motor Vehicle Collision. Clin J Pain 31:768-775

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