Pain, but not Physical Activity, is Associated with Gray Matter Volume Differences in Gulf War Veterans with Chronic Pain.

Chronic musculoskeletal pain (CMP) is a significant burden for Persian Gulf War Veterans (GWV), yet the causes are poorly understood. Brain structure abnormalities are observed in GWV, however relationships with modifiable lifestyle factors such as physical activity (PA) are unknown. We evaluated gray matter volumes and associations with symptoms, PA, and sedentary time in GWV with and without CMP. Ninety-eight GWV (10 females) with CMP and 56 GWV (7 females) controls completed T1 weighted magnetic resonance imaging, pain and fatigue symptom questionnaires, and PA measurement via actigraphy. Regional gray matter volumes were analyzed using voxel-based morphometry and were compared across groups using analysis of covariance. Separate multiple linear regression models were used to test associations between PA intensities, sedentary time, symptoms, and gray matter volumes. Family-wise cluster error rates were used to control for multiple comparisons (α=0.05). GWV with CMP reported greater pain and fatigue symptoms, worse mood, and engaged in less moderate-to-vigorous PA and more sedentary time than healthy GWV (all p<0.05). GWV with CMP had smaller gray matter volumes in the bilateral insula and larger volumes in the frontal pole (p<0.05adjusted). Gray matter volumes in the left insula were associated with pain symptoms (rpartial=0.26, -0.29; p<0.05adjusted). No significant associations were observed for either PA or sedentary time (p>0.05adjusted). GWV with CMP had smaller gray matter volumes within a critical brain region of the descending pain processing network and larger volumes within brain regions associated with pain sensation and affective processing which may reflect pain chronification.Significance Statement:The pathophysiology of chronic pain in Gulf War Veterans is understudied and not well understood. In a large sample of Gulf War Veterans, we report Veterans with chronic musculoskeletal pain have smaller gray matter volumes in brain regions associated with pain regulation and larger volumes in regions associated with pain sensitivity compared to otherwise healthy Gulf War Veterans. Gray matter volumes in regions of pain regulation were significantly associated with pain symptoms and encompassed the observed group brain volume differences. These results are suggestive of deficient pain modulation that may contribute to pain chronification.

The Feasibility and Effectiveness of a Community-Based Intervention to Reduce Sedentary Behavior in Older Adults.

The purpose of this study was to examine the effectiveness and feasibility of translating a 4-week "Stand Up and Move More" (SUMM) intervention by state aging units to older adults (N = 56, M age = 74 years). A randomized controlled trial assessed sedentary behavior, physical function, and health-related quality of life (HRQoL) before and after the intervention. Participants included healthy community-dwelling, sedentary (sit > 6 hr/day) and aged ≥ 55 years adults. For the primary outcome, the SUMM group (n = 31) significantly (p < .05) reduced total sedentary time post-intervention by 68 min/day on average (Cohen's d = -0.56) compared with no change in the wait-list control group (n = 25, Cohen's d = 0.12). HRQoL and function also improved (p < .05) in the SUMM group post-intervention. Workshop facilitators indicated the intervention was easy to implement, and participants expressed high satisfaction. The SUMM intervention reduced sedentary time, improved physical function and HRQoL, and was feasible to implement in community settings.

Exercise-induced increases in Anandamide and BDNF during extinction consolidation contribute to reduced threat following reinstatement: Preliminary evidence from a randomized controlled trial.

INTRODUCTION: We recently demonstrated that moderate-intensity aerobic exercise delivered during the consolidation of fear extinction learning reduced threat expectancy during a test of extinction recall among women with posttraumatic stress disorder (PTSD). These findings suggest that exercise may be a potential candidate for improving the efficacy of exposure-based therapies, which are hypothesized to work via the mechanisms of fear extinction learning. The purpose of this secondary analysis was to examine whether exercise-induced increases in circulating concentrations of candidate biomarkers: endocannabinoids (anandamide [AEA]; 2-arachidonoylglycerol [2-AG], brain-derived neurotrophic factor (BDNF), and homovanillic acid (HVA), mediate the effects of exercise on extinction recall. METHODS: Participants (N = 35) completed a 3-day fear acquisition (day 1), extinction (day 2), and extinction recall (day 3) protocol, in which participants were randomly assigned to complete either moderate-intensity aerobic exercise (EX) or a light-intensity control (CON) condition following extinction training (day 2). Blood was obtained prior to and following EX or CON. Threat expectancy ratings during tests of extinction recall (i.e., initial fear recall and fear recall following reinstatement) were obtained 24 h following EX or CON. Mediation was tested using linear-mixed effects models and bootstrapping of the indirect effect. RESULTS: Circulating concentrations of AEA and BDNF (but not 2-AG and HVA) were found to mediate the relationship between moderate-intensity aerobic exercise and reduced threat expectancy ratings following reinstatement (AEA 95% CI: -0.623 to -0.005; BDNF 95% CI: -0.941 to -0.005). CONCLUSIONS: Exercise-induced increases in peripheral AEA and BDNF appear to play a role in enhancing consolidation of fear extinction learning, thereby leading to reduced threat expectancies following reinstatement among women with PTSD. Future mechanistic research examining these and other biomarkers (e.g., brain-based biomarkers) is warranted.

Safety and efficacy of short-term structured resistance exercise in Gulf War Veterans with chronic unexplained muscle pain: A randomized controlled trial.

AIMS: Chronic widespread musculoskeletal pain (CMP) is a primary condition of Veterans suffering from Gulf War illness. This study evaluated the influence of resistance exercise training (RET) on symptoms, mood, perception of improvement, fitness, and total physical activity in Gulf War Veterans (GWV) with CMP. MAIN METHODS: Fifty-four GWV with CMP were randomly assigned to 16 weeks of RET (n = 28) or wait-list control (n = 26). Supervised exercise was performed twice weekly starting at a low intensity. Outcomes, assessed at baseline, 6, 11 and 17 weeks and 6- and 12-months post-intervention, were: pain, fatigue, mood, sleep quality, perception of improvement, and physical activity via self-report and accelerometry. Muscular strength was assessed at baseline, 8 and 16 weeks. Accelerometer data yielded estimates of time spent in sedentary, light, and moderate-to-vigorous physical activities. Analyses used separate linear mixed models with group and time point as fixed effects. All models, except for perceived improvement, included baseline values as a covariate. KEY FINDINGS: Participants assigned to RET completed 87% of training sessions and exhibited strength increases between 16 and 34% for eight lifts tested (Hedges' g range: 0.47-0.78). The treatment by time interaction for perceived improvement (F1,163 = 16.94, p < 0.001) was characterized by greater perceived improvement since baseline for RET at each time point, until the 12-month follow-up. Effects were not significant for other outcomes (p > 0.05). RET caused no adverse events. SIGNIFICANCE: After 16 weeks of RET, GWV with CMP reported improvements in their condition and exhibited increases in muscular strength, without symptom exacerbation or reductions in total physical activity.

Post-exertional malaise in veterans with gulf war illness.

Post-exertional malaise (PEM) is a potentially debilitating aspect of Gulf War Illness (GWI) that has received limited research attention. The purpose of the present investigation was to determine symptom severity changes following exercise in Veterans with GWI compared to control Veterans without GWI (CO). Sixty-seven Veterans (n = 39 GWI; n = 28 CO) underwent a 30-minute submaximal exercise challenge at 70% of heart rate reserve. Symptom measurements (e.g. fatigue, pain) occurred pre-, immediately post-, and 24-hour post-exercise. Self-reported physical and mental health, and physiological and perceptual responses to exercise were compared between groups using descriptive statistics, independent samples t-tests and repeated measures Analysis of Variance (RM-ANOVA). Post-exertional malaise was modeled using Group by Time (2 × 3) doubly-multivariate, RM-MANOVAs for (1) mood, (2) pain and (3) GWI-related symptoms, respectively (α = 0.05). Data were analyzed for the full sample of Veterans with GWI (n = 39) compared to CO (n = 28) and a subsample of Veterans (n = 18) who endorsed "feeling unwell after physical exercise or exertion" ("PEM endorsers") during screening. Veterans with GWI reported significantly lower physical and mental health. Groups exercised at similar relative exercise intensities, but GWI perceived exercise as more painful and fatiguing. Group-by-Time interactions were not significant for the entire sample for the three PEM models, however limiting the GWI sample to "PEM endorsers" resulted in significant interactions for Pain- and GWI-related PEM models. These results indicate that not all GVs with GWI experience PEM 24 h after exercise, and that more research is needed to determine the extent that exercise worsens symptoms in GWI.

Translating a "Stand Up and Move More" intervention by state aging units to older adults in underserved communities: Protocol for a randomized controlled trial.

INTRODUCTION: As aging is associated with functional decline, preventing functional limitations and maintaining independence throughout later life has emerged as an important public health goal. Research indicates that sedentary behavior (prolonged sitting) is associated with functional loss and diminished ability to carry out activities of daily living. Despite many efforts to increase physical activity, which can be effective in countering functional loss, only an estimated 8% of older adults meet national physical activity guidelines. Thus, shifting the focus to reducing sitting time is emerging as a potential new intervention strategy but little research has been conducted in this area. With community support and funding, we developed and pilot tested a 4-week "Stand Up and Move More" intervention and found decreases in sedentary behavior, increases in physical activity, and improvements in mobility and vitality in a small sample of older adults. The purpose of this project is to expand upon these pilot results and examine the effectiveness and feasibility of translating a "Stand Up and Move More" intervention by State Aging Units to older adults in underserved communities. Eighty older adults from 4 counties across Wisconsin predominantly made up of rural older adults and older African American adults are randomly assigned to intervention (n = 40) or wait-list control (n = 40) groups. The intervention consists of 4 weekly sessions plus a refresher session at 8 weeks, and is delivered by community partners in each county. The sessions are designed to elicit ideas from older adults regarding how they can reduce their sitting time, help them set practical goals, develop action plans to reach their goals, and refine their plans across sessions to promote behavior change. Sedentary behavior, physical activity levels, functional performance, and health-related quality of life are assessed before and after the intervention to examine the effectiveness of the program. Feasibility of implementing the program by our community partners is assessed via semi-structured interviews. Strengths of this project include strong community collaborations and a high need given that the older adult population is projected to increase substantially in the next 15 years. CONCLUSION: This project will provide an important step in developing effective strategies for maintaining independence in older adults through determining the feasibility and impact of a community-based intervention to break up sitting time.