Impact of Exercise Training on Pain and Brain Function in Gulf War Veterans
Condition: Chronic Musculoskeletal Pain
MeSH terms: Musculoskeletal Pain
Study type: Interventional

Summary: 
      This study is intended to test the influence of weight training on physical symptoms,
      physical activity and brain structure and function in Gulf War Veterans with chronic
      widespread muscle pain.
    

Detailed description: 
      Musculoskeletal pain in soldiers who returned from the Persian Gulf War is a serious problem.
      Numerous studies have reported musculoskeletal pain as a primary symptom of sick Gulf
      Veterans (GVs), with ~100,000 Veterans (~15%) reporting unresolved pain affecting their
      social and professional lives. Pain and other symptoms are often disabling with 1 in 7 United
      States Veterans seeking care for war-related health concerns and ~12% receiving disability
      compensation. Thus, a significant number of military personnel are no longer able to perform
      their duties due to medically unexplained symptoms including pain, fatigue and cognitive
      problems. Importantly, recent evidence suggests that chronic pain complaints in most GVs have
      not resolved. Similar problems appear to be on the horizon for Veterans from Operations
      Enduring and Iraqi Freedom. Understanding the pathophysiological consequences of chronic
      muscle pain is important for better determining both the efficacy and mechanism of treatments
      aimed at decreasing debilitating symptoms and improving physical function among Veterans
      coping with chronic pain.

      Given the dearth of experimental data in GVs with chronic musculoskeletal pain (CMP), we have
      patterned much of our research in GVs after our research in fibromyalgia (FM), a disorder
      with a primary symptom of muscle and joint pain in civilians. Our work and the work of others
      suggest that FM pain is produced and maintained by central nervous system (CNS) dysregulation
      of nociceptive and pain processes. Our work also suggests that phenomena similar to those
      observed in FM may be occurring in GVs with CMP. Like FM patients, GVs with CMP, 1) are more
      sensitive to experimental pain stimuli, 2) exhibit exaggerated pain responses following acute
      exercise, 3) experience more muscle pain during acute exercise and 4) show augmented brain
      responses to both painful and non-painful experimental stimuli. These data suggest that some
      of the same pathophysiological mechanisms involved in FM may be maintaining chronic
      widespread muscle pain in GVs. Critical unanswered questions include whether promising
      treatments for CMP in GVs can affect laboratory measures of pain sensitivity and pain
      regulation and whether these changes relate to clinical improvements. We intend to begin to
      answer these questions by examining perceptual and brain hemodynamic responses to
      standardized painful stimuli and documenting their relationships to clinical outcomes before,
      during and upon completion of a viable, novel treatment for CMP.

      There are no known efficacious treatments for GVs suffering CMP. Efficacy studies are needed
      to begin determining effective treatments for our Veterans following their service of our
      country. In FM, exercise training (both aerobic and resistance modes) is widely recognized as
      one of the few consistently efficacious treatments, resulting in improved well-being,
      increased physical function and in some cases decreased pain. One large scale treatment trial
      of aerobic exercise in GVs with chronic multi-symptom illness showed only modest improvements
      in pain, fatigue and mental health. We believe this trial had several limitations that
      greatly attenuated the treatment's effectiveness; consequently, it is premature to discount
      exercise training as a treatment for GVs with CMP. Further, we propose a novel approach that
      employs progressive resistance exercise training (RET) to treat GVs with CMP, while obtaining
      objective measures of nociceptive function, brain white matter tract pathways and total
      physical activity.

      In addition to exercise performed as part of a structured training program, physical activity
      behaviors are important determinants of physical and mental health. Greater total physical
      activity levels are associated with increased physical function, improved mental health,
      increased energy and decreased symptoms of chronic pain. To our knowledge, none of the
      exercise training trials in FM have actually measured the impact of the exercise training on
      physical activity behaviors during daytime hours outside the intervention. It is plausible
      that the adoption of a structured exercise training program reduces physical activities
      performed during the rest of the day, and that this change in total physical activity could
      affect health outcomes. Objective measurement of physical activity will allow us to determine
      whether RET increases, decreases or has no impact on total physical activity levels in GVs
      with CMP. This will allow us to begin to characterize sub-groups who benefit the most from
      RET (e.g. potentially those GVs that maintain or increase their extra-intervention physical
      activity). Thus, in addition to supervised RET, we will objectively measure total physical
      activity levels outside of the intervention using accelerometers before, during and following
      treatment.

      In summary, we propose to determine the efficacy of RET for the treatment of CMP and
      associated symptoms in GVs. In addition, we will assess the influence of RET on total
      physical activity, pain sensitivity and regulation, and brain white matter tracts. By
      applying functional neuroimaging techniques in conjunction with pain psychophysics we will
      test how the brains of Veterans with CMP respond to sensory stimuli and whether these
      responses can be modified by exercise training. We plan to use blood oxygen level dependent
      (BOLD) and diffusion tensor imaging (DTI) methods to evaluate the function of brain regions
      involved in pain processing and control and the microstructural properties of white matter
      tract pathways that connect these regions. In addition, we will determine the influence of
      RET on extra-intervention physical activity behaviors, testing a critical and unanswered
      question - whether total physical activity levels change as a result of engaging in a RET
      program in patients with CMP. The primary goals of this project will be accomplished by
      comparing GVs with CMP assigned to either RET or wait-list control (WLC) in a randomized
      controlled trial.
    

Intervention name(s): Resistance Exercise Training
Intervention type(s): Behavioral
Intervention description(s): 16 weeks of resistance exercise training for the treatment of chronic muscle pain compared to wait-list control
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: pain; brain imaging; exercise