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.

Mortality risk and physical activity across the lifespan in endometrial cancer survivors.

PURPOSE: Physical activity (pre- and post-diagnosis) has been studied in prevention and survivorship contexts for endometrial cancer. However, the association of physical activity (PA) across the lifespan on mortality risk among endometrial cancer survivors is understudied. The study's objective was to identify the association of lifetime PA on mortality risk in endometrial cancer survivors. METHODS: Seven hundred forty-five endometrial cancer survivors drawn from a population-based cancer registry (diagnosed between 1991 and 1994) reported the frequency (sessions/week) of moderate- and vigorous intensity physical activity (MVPA) at age 12, age 20, and 5 years pre-interview (post-diagnosis). Cox proportional hazards were used to estimate hazard ratios (HR) and 95% confidence intervals for the association between PA, all-cause, and cardiovascular disease mortality as assessed in 2016. MVPA was modeled using natural cubic splines. RESULTS: Diagnosis age, body mass index, and smoking (pack-years) were each positively associated with increased all-cause mortality risk. Those who did one session of MVPA 5 years pre-interview had a lower mortality risk (HR 0.61; 95% CI 0.41-0.92) compared to those with no MVPA. Those reporting one session of MVPA was similarly observed at age 12 (HR 0.95; 95% CI 0.86-1.06) and at age 20 (HR 0.87; 95% CI 0.65-1.16). CONCLUSION: Those who participated in PA, compared to those who did not, in the 5 years before diagnosis had a lower mortality risk. While PA was not independently protective against mortality risk at ages 12 or 20, PA is still important for endometrial cancer survivors for other non-mortality outcomes.

Improvements in strength and agility measures of functional fitness following a telehealth-delivered home-based exercise intervention in endometrial cancer survivors.

PURPOSE: Endometrial cancer is strongly linked to obesity and inactivity; however, increased physical activity has important benefits even in the absence of weight loss. Resistance (strength) training can deliver these benefits; yet few women participate in resistance exercise. The purpose of this study was to describe both physiological and functional changes following a home-based strength training intervention. METHODS: Forty post-treatment endometrial cancer survivors within 5 years of diagnosis were enrolled in a pilot randomized trial, comparing twice-weekly home-based strength exercise to wait list control. Participants conducted the exercises twice per week for 10 supervised weeks with 5 weeks of follow-up. Measures included DXA-measured lean mass, functional fitness assessments, blood biomarkers, and quality of life outcomes. RESULTS: On average, participants were 60.9 years old (SD = 8.7) with BMI of 39.9 kg/m2 (SD = 15.2). At baseline, participants had 51.2% (SD = 6.0) body fat, which was not different between groups. Improvements were seen in the 30-s chair sit to stand (d = .99), the 30-s arm curl (d = .91), and the 8-ft up-and-go test (d = .63). No changes were measured for HbA1c or C-reactive protein. No changes were observed for flexibility (chair sit and reach, back scratch tests), 6-min walk test, maximum handgrip test, anxiety, depression, fatigue, or self-efficacy for exercise. CONCLUSIONS: Home-based muscle-strengthening exercise led to favorable and clinically relevant improvements in 3 of 7 physical function assessments. Physical function, body composition, blood biomarkers, and patient-reported outcomes were feasible to measure. These fitness improvements were observed over a relatively short time frame of 10 weeks.

Psychological and endocannabinoid responses to aerobic exercise in substance use disorder patients.

BACKGROUND: Exercise has been examined as an adjunctive treatment for substance use disorders (SUDs), yet few exercise interventions have been conducted among patients undergoing intensive outpatient (IOP) treatment, who may be the most vulnerable to relapse and for whom exercise could provide the most benefits. This study examined the effects of aerobic exercise, in addition to IOP treatment, on psychological variables and endocannabinoids in individuals with SUDs. Methods: Twenty-one SUD patients (mean age 35 years) were recruited from local IOPs. Participants were randomized to either treatment-as-usual (TAU, at their outpatient clinic) or TAU plus aerobic exercise training (EX). EX participants engaged in supervised, moderate-intensity exercise for 30 min, 3 times/week for 6 weeks. TAU participants came into the laboratory once per week for assessments and a 30-min quiet rest session. Participants provided blood samples and completed questionnaires evaluating substance use, mood states, depression, anxiety, perceived stress, self-efficacy to abstain from substance use, and craving. Data were analyzed with Mann-Whitney U tests or mixed model ANOVAs to determine group differences in outcomes acutely and over 6 weeks. Results: Over 6 weeks, there were reductions in perceived stress (p < 0.01) and craving (p < 0.05) for both groups. There were no group differences in abstinence rates or changes from baseline in self-efficacy, depression, or anxiety (p > 0.05). Acutely, both exercise and quiet rest sessions led to reductions in craving, tension, depression, anger, confusion, and total mood disturbance (all ps < 0.05). In addition, the EX group experienced acute increases in vigor and circulating concentrations of the endocannabinoid, anandamide (p < 0.01). Conclusions: An adjunctive aerobic exercise program during SUD treatment was associated with similar reductions in perceived stress and drug craving as standard care. Thirty minutes of exercise or quiet rest led to acute improvements in mood, but exercise produced the additional benefit of increases in vigor and circulating anandamide.

Endocannabinoid and Opioid System Interactions in Exercise-Induced Hypoalgesia.

Objective: The purpose of this study was to examine the interaction between the endogenous opioid and endocannabinoid (eCB) systems in a pain modulatory process known as exercise-induced hypoalgesia (EIH). Design: Randomized controlled trial. Setting: Clinical research unit in a hospital. Subjects: Fifty-eight healthy men and women (mean age = 21 ± 3 years) participated in this study. Methods: Participants were administered (randomized, double-blind, counterbalanced procedure) an opioid antagonist (i.e., naltrexone) and a placebo prior to performing pain testing and isometric exercise. Results: Results indicated that 2-arachidonoylglycerol (2-AG) and 2-oleoylglycerol (2-OG) increased significantly (P < 0.05) following exercise in both placebo and naltrexone conditions. In comparison, N-arachidonylethanolamine (AEA) and oleoylethanolamine (OEA) increased significantly (P < 0.05) following exercise in the placebo condition but not the naltrexone condition. There were no significant (P > 0.05) differences in palmitolethanolamine (PEA) between the placebo and naltrexone conditions. Conclusions: As reductions in pain (i.e., EIH) were observed following both conditions, these results suggest that the opioid system may not be the primary system involved in exercise-induced hypoalgesia and that 2-AG and 2-OG could contribute to nonopioid exercise-induced hypoalgesia. Moreover, as exercise-induced increases in AEA and OEA were blocked by naltrexone pretreatment, this suggests that the opioid system may be involved in the increase of AEA and OEA following exercise.

Psychobiological Responses to Aerobic Exercise in Individuals With Posttraumatic Stress Disorder.

Previous reports have shown improvements in mood and increases in endocannabinoids in healthy adults following a session of aerobic exercise, but it is unclear whether adults with posttraumatic stress disorder (PTSD) experience similar responses. The purpose of this study was to examine psychobiological responses (plasma endocannabinoids [eCBs], mood, and pain) to aerobic exercise in a sample of adults with a diagnosis of PTSD (n = 12) and healthy controls (n = 12). Participants engaged in an aerobic exercise session in which they ran on a treadmill for 30 min at a moderate intensity (70 to 75% maximum heart rate [MHR]). Results indicated improvements in mood states and reductions in pain for both groups following exercise, ds = 0.19 to 1.53. Circulating concentrations of N-arachidonylethanolamine (AEA), 2-arachidonoylglycerol (2-AG), and oleoylethanolamide (OEA) significantly increased (ps = .000 to .050) following the aerobic exercise session for both groups. There were no significant time, group, or interaction effects (ps = .062 to .846) for palmitoylethanolamide (PEA) and 2-oleoylglycerol (2-OG). Although eCBs increased significantly for both groups, within-group effect size calculations indicated the healthy controls experienced a greater magnitude of change for AEA when compared with adults with PTSD, d = 1.21 and d = 0.45, respectively; as well as for 2-AG, d = 0.43 and d = 0.21, respectively. The findings from this study indicated that adults with and without PTSD reported significant mood improvements following 30 min of moderate-intensity aerobic exercise. In addition, the endocannabinoid system was activated in adults with and without PTSD, although effect sizes suggest that adults with PTSD may have a blunted endocannabinoid response to exercise.

Psychosocial Influences on Exercise-Induced Hypoalgesia.

Objective: The purpose of this study was to examine psychosocial influences on exercise-induced hypoalgesia (EIH). Design: Randomized controlled trial. Setting: Clinical research unit in a hospital. Subjects: Fifty-eight healthy men and women (mean age = 21 ± 3 years) participated in this study. Methods: Participants were first asked to complete a series of baseline demographic and psychological questionnaires including the Pain Catastrophizing Scale, the Fear of Pain Questionnaire, and the Family Environment Scale. Following this, they were familiarized with both temporal summation of heat pain and pressure pain testing protocols. During their next session, participants completed the Profile of Mood States, rated the intensity of heat pulses, and indicated their pressure pain thresholds and ratings before and after three minutes of submaximal, isometric exercise. Situational catastrophizing was assessed at the end of the experimental session. Results: Results indicated that experimental pain sensitivity was significantly reduced after exercise ( P < 0.05). Men and women did not differ on any of the measured psychosocial variables ( P > 0.05). Positive family environments predicted attenuated pain sensitivity and greater EIH, whereas negative and chronic pain-present family environments predicted worse pain and EIH outcomes. Situational catastrophizing and negative mood state also predicted worse pain and EIH outcomes and were additionally associated with increased ratings of perceived exertion and muscle pain during exercise. Conclusions: This study provides preliminary evidence that psychosocial variables, such as the family environment and mood states, can affect both pain sensitivity and the ability to modulate pain through exercise-induced hypoalgesia.

Exercise as an adjunctive treatment for cannabis use disorder.

BACKGROUND: Despite cannabis being the most widely used illicit substance in the United States, individuals diagnosed with cannabis use disorder (CUD) have few well-researched, affordable treatment options available to them. Although found to be effective for improving treatment outcomes in other drug populations, exercise is an affordable and highly accessible treatment approach that has not been routinely investigated in cannabis users. OBJECTIVES: The aim of this paper is to inform the topic regarding exercise's potential as an adjunctive treatment for individuals with CUD. METHODS: We reviewed the evidence surrounding cannabis use and its current treatment in the United States, explored the rationale for including exercise in the treatment of substance use disorders (SUDs), and in particular, proposed a biological mechanism (i.e., endocannabinoids (eCBs)) that should be examined when utilizing exercise for the treatment of CUD. RESULTS: Cannabis use is widespread and increasing in the United States. Chronic, heavy cannabis use may dysregulate the endogenous cannabinoid system, which has implications for several psychobiological processes that interact with the eCB system such as reward processing and the stress response. Given that exercise is a potent activator of the eCB system, it is mechanistically plausible that exercise could be an optimal method to supplement cessation efforts by reducing psychophysical withdrawal, managing stress, and attenuating drug cravings. CONCLUSION: We suggest there is a strong behavioral and physiological rationale to design studies which specifically assess the efficacy of exercise, in combination with other therapies, in treating CUD. Moreover, it will be especially important to include the investigation of psychobiological mechanisms (e.g., eCBs, hippocampal volume), which have been associated with both exercise and SUDs, to examine the broader impact of exercise on behavioral and physiological responses to treatment.

Inducing a blind spot: blinding data collectors in an investigation of experimental pain.

OBJECTIVE: Methods of blinding have been infrequently investigated. This study assessed data collector blinding within an investigation of endogenous pain modulation. DESIGN: Participants (N = 33; 52% women) were randomly assigned to an order of an exercise bout with intramuscular control injections, quiet rest with intramuscular algesic injections, and a control condition. Data collectors (N = 4; 50% women) recorded participants' pain responses and then left the room before the injection and exercise procedures were administered by other personnel. Immediately after the procedures, the data collectors returned to collect additional pain responses and record their suspicions regarding the assigned condition, their confidence level in their suspicions (0-100 mm scale), and the reason/s for their suspicions. RESULTS: Data collectors correctly identified control and algesic injections in 90.4 and 73.1% of the sessions, respectively, and quiet rest and exercise in 94.2 and 69.2% of the sessions, respectively. The confidence of the data collectors in their suspicions was 60.17 mm (SD = 34.54) for injections and 62.19 mm (SD = 34.95) for exercise. However, data collectors only had correct suspicions and confidence of at least 90 mm for 26.2% of the injections and 29.4% of the exercise bouts. Participants' pain responses were the primary reason for data collectors' suspicions. Neither the amount of experience nor the sexual composition of the participant-data collector dyad influenced the blinding. CONCLUSIONS: Collection of participants' pain responses led to frequent episodes of unblinding. However, it may be misleading to only consider the frequency of correct suspicions as successful or unsuccessful blinding.

Intervening to reduce sedentary behavior among African American elders: the "Stand Up and Move More" intervention.

Background: Reducing sedentary behavior is a promising intervention target for improving health for older adults; however, few interventions include African American communities. The purpose of this research was to extend the reach of an effective sedentary behavior intervention to African American elders. Methods: Two pilot studies assessed the feasibility (retention, adherence, and safety) and acceptability (participant and leader perspectives) of a 4-wk "Stand Up and Move More" (SUMM) intervention. Sedentary behavior (self-reported and monitor-derived), function (short physical performance battery), and quality of life (SF-36) were measured at baseline (wk0), postintervention (wk4), and follow up (wk12; study 1) to examine preliminary effectiveness of the intervention. Participants (N=26) attended SUMM or an attention-matched stress management intervention (study 2). The magnitude of treatment effects were determined using Hedge's g effect size calculations [small (g=0.20 to 0.49), moderate (g=0.50 to 0.79), large (g>0.80)]. Results: Retention and adherence rates ranged from 50%-100% and 80%-100%, respectively. There were no adverse events. Participants expressed high satisfaction, and the leader of the SUMM intervention indicated that the intervention content was beneficial. Hedges' g revealed negligible to small changes in sedentary behavior (g<0.50) following SUMM. There were moderate to large improvements in function (g=0.51-0.82) and quality of life (g=0.54-1.07) from wk0 to wk4 in study 1; and moderate to large improvements in function (g=0.51-0.88) from wk0 to wk4 in study 2. There was a moderate improvement in quality of life (SF-36 emotional role limitations g=0.54) in the SUMM group only. Conclusion: Given its feasibility, safety, and acceptability, SUMM may be a promising intervention to improve functioning and well-being among African American elders.

The role of spontaneous vs. experimentally induced attentional strategies for the pain response to a single bout of exercise in healthy individuals.

OBJECTIVES: Exercise-induced pain and exercise-induced hypoalgesia (EIH) are well described phenomena involving physiological and cognitive mechanisms. Two experiments explored whether spontaneous and instructed mindful monitoring (MM) were associated with reduced exercise-induced pain and unpleasantness, and increased EIH compared with spontaneous and instructed thought suppression (TS) in pain-free individuals. METHODS: Eighty pain-free individuals participated in one of two randomized crossover experiments. Pressure pain thresholds (PPTs) were assessed at the leg, back and hand before and after 15 min of moderate-to-high intensity bicycling and a non-exercise control condition. Exercise-induced pain and unpleasantness were rated after bicycling. In experiment 1 (n=40), spontaneous attentional strategies were assessed with questionnaires. In experiment 2, participants (n=40) were randomly allocated to use either a TS or MM strategy during bicycling. RESULTS: In experiment 1, the change in PPTs was significantly larger after exercise compared with quiet rest (p<0.05). Higher spontaneous MM was associated with less exercise-induced unpleasantness (r=-0.41, p<0.001), whereas higher spontaneous TS was associated with higher ratings of exercise-induced unpleasantness (r=0.35, p<0.05), but not with pain intensity or EIH. In experiment 2, EIH at the back was increased in participants using instructed TS compared with participants using instructed MM (p<0.05). CONCLUSIONS: These findings suggest that spontaneous and presumably habitual (or dispositional) attentional strategies may primarily affect cognitive-evaluative aspects of exercise, such as feelings of exercise-induced unpleasantness. MM was related to less unpleasantness, whereas TS was related to higher unpleasantness. In terms of brief experimentally-induced instructions, TS seems to have an impact on physiological aspects of EIH; however, these preliminary findings need further research.

Feasibility and acceptability of home-based strength training in endometrial cancer survivors.

PURPOSE: Physical activity is important for healthy cancer survivorship, yet many endometrial cancer survivors do not participate in recommended muscle-strengthening activity. The purpose of this study was to determine the feasibility of home-based muscle strengthening activity in endometrial cancer survivors. METHODS: Forty post-treatment endometrial cancer survivors were enrolled in a randomized trial, of twice-weekly home-based strength exercise versus wait-list control. The intervention included educational materials, exercise equipment (dumbbells, resistance bands), and support/feedback via video coaching sessions. Participants completed the exercises twice per week for 10 weeks, with a 5-week follow-up period. Feasibility was measured by program adherence, as well as safety of and satisfaction with the study. RESULTS: On average, participants were 60.9 years old (SD = 8.7), had a BMI of 39.9 kg/m2 (SD = 15.2), and were 2.9 years (SD = 1.2) since diagnosis. The majority (83%) had stage I disease at diagnosis. Seventy-five percent adhered to the exercise prescription of twice/week, with 85% of participants missing fewer than 3 of the workouts. Forty percent of participants continued workouts during the 5-week follow-up. Participants were highly satisfied with intervention. No injuries or adverse everts occurred. CONCLUSION: This home-based program was feasible in endometrial cancer survivors. While adherence was measured, future research should focus on long-term maintenance of exercise and should explore progressions and modifications of exercises at a distance for various abilities. IMPLICATIONS FOR CANCER SURVIVORS: Muscle strengthening activities are recommended for all cancer survivors. This study shows that a home-based muscle strengthening exercise is feasible in endometrial cancer survivors.

Circulating endocannabinoids and psychological outcomes in women with PTSD.

BACKGROUND: Recent research has attempted to elucidate the relationship between blood-based biomarkers (e.g., endocannabinoids; eCBs: including N-arachidonoylethanolamine [AEA] and 2-arachidonoylglycerol [2-AG]) and mental health outcomes in psychiatric populations such as posttraumatic stress disorder (PTSD). Prior research suggests that adults with PTSD may have altered circulating eCB tone and a blunted mobilization of eCBs (particularly 2-AG) in response to stress (e.g., aerobic exercise), although our understanding has been limited in part due to heterogenous samples and small sample sizes. METHODS: A subset of data was pooled from five studies in which women with and without PTSD (N = 98) completed questionnaires related to mood states and a blood draw prior to and following a bout of moderate-intensity aerobic exercise in order to determine: 1) whether circulating eCBs differ between groups and whether depressive and PTSD symptom severity are associated with baseline eCBs, 2) whether a bout of aerobic exercise increases circulating eCBs in adult women with PTSD, and 3) whether circulating eCBs are associated with overall mood states and exercise-induced improvements in mood states in women with and without PTSD. RESULTS: PTSD diagnoses were not associated with baseline concentrations of eCBs. Greater depressive symptom severity and PTSD symptom severity within the negative alteration in cognition and mood cluster were associated with lower circulating AEA. Circulating AEA significantly increased following aerobic exercise for both groups, whereas circulating 2-AG only increased in women without PTSD. Greater circulating AEA within the PTSD group was associated with lower depressive mood, confusion, and total mood disturbance. CONCLUSIONS: These findings suggest that greater circulating AEA is associated with better overall mood and lower depressive and PTSD symptom severity, and that an acute bout of moderate-intensity aerobic exercise increases circulating AEA (but not 2-AG) in adult women with PTSD. These findings are consistent with the idea that greater eCB tone (particularly AEA) following pharmacological and/or non-pharmacological manipulations may be beneficial for improving psychological outcomes (e.g., mood, cognition) among PTSD, and possibly other psychiatric populations.

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 and Neuropathic Pain: A General Overview of Preclinical and Clinical Research.

Neuropathic pain is a disease of the somatosensory system that is characterized by tingling, burning, and/or shooting pain. Medication is often the primary treatment, but it can be costly, thus there is an interest in understanding alternative low-cost treatments such as exercise. The following review includes an overview of the preclinical and clinical literature examining the influence of exercise on neuropathic pain. Preclinical studies support the hypothesis that exercise reduces hyperalgesia and allodynia in animal models of neuropathic pain. In human research, observational studies suggest that those who are more physically active have lower risk of developing neuropathic pain compared to those who are less active. Exercise studies suggest aerobic exercise training (e.g., 16 weeks); a combination of aerobic and resistance exercise training (e.g., 10-12 weeks); or high-intensity interval training (e.g., 15 weeks) reduces aspects of neuropathic pain such as worst pain over the past month, pain over the past 24 h, pain scores, or pain interference. However, not all measures of pain improve following exercise training (e.g., current pain, heat pain threshold). Potential mechanisms and future directions are also discussed to aid in the goal of understanding the role of exercise in the management of neuropathic pain. Future research using standardized methods to further understanding of the dose of exercise needed to manage neuropathic pain is warranted.

Aerobic exercise reduces anxiety and fear ratings to threat and increases circulating endocannabinoids in women with and without PTSD.

Reductions in state anxiety have been reported following an acute bout of aerobic exercise. However, less is known regarding anxiety and fear ratings to specific threatening stimuli following an acute bout of aerobic exercise in women with PTSD. Moreover, the mechanisms responsible for the anxiolytic effects of exercise are not fully understood, although recent studies suggest a role for the endocannabinoid (eCB) system. Thus, this study utilized a randomized, counterbalanced approach to examine anxiety and fear ratings to predictable or unpredictable electric shock administration and circulating concentrations of eCBs and mood states immediately following moderate-intensity aerobic exercise (30 min on treadmill at 70-75% maximum heart rate) and a quiet rest control condition in women with and without a history of trauma, and in women with PTSD (N=42). Results revealed that anxiety and fear ratings to unpredictable and predictable threats were significantly (p<.05) lower following exercise compared to quiet rest, with correlational analyses indicating those with greater increases in circulating eCBs had greater reductions in anxiety and fear ratings to unpredictable and predictable threats following exercise. Also, there were significant (p<.05) reductions in fatigue, confusion, total mood disturbance, and increases in positive affect following exercise for the entire sample. Non-trauma controls and PTSD groups reported significant (p<.05) increases in vigor, with additional mood improvements following exercise for the PTSD group (i.e., decreases in state anxiety, negative affect, tension, anger, and depression). Results from this study suggest that aerobic exercise exerts psychological benefits in women with PTSD, potentially due to exercise-induced increases in circulating concentrations of eCBs.

Does aerobic exercise training alter responses to opioid analgesics in individuals with chronic low back pain? A randomized controlled trial.

ABSTRACT: We tested whether aerobic exercise training altered morphine analgesic responses or reduced morphine dosages necessary for adequate analgesia. Patients with chronic back pain were randomized to an 18-session aerobic exercise intervention (n = 38) or usual activity control (n = 45). Before and after the intervention, participants underwent 3 laboratory sessions (double-blinded, crossover) to assess effects of saline placebo, i.v. morphine (0.09 mg/kg), and i.v. naloxone (12 mg) on low back pain and evoked heat pain responses. Differences in evoked and back pain measures between the placebo and morphine conditions indexed morphine analgesia, with pre-post intervention changes the primary outcome. Endogenous opioid analgesia was indexed by differences in evoked and low back pain measures between the naloxone and placebo conditions. A Sex X Intervention interaction on the analgesic effects of morphine on visual analogue scale back pain intensity was observed (P = 0.046), with a similar trend for evoked pain threshold (P = 0.093). Male exercisers showed reduced morphine analgesia pre-post intervention, whereas male controls showed increased analgesia (with no differences in females). Of clinical significance were findings that relative to the control group, aerobic exercise produced analgesia more similar to that observed after receiving ≈7 mg morphine preintervention (P < 0.045). Greater pre-post intervention increases in endogenous opioid function (from any source) were significantly associated with larger pre-post intervention decreases in morphine analgesia (P < 0.046). The overall pattern of findings suggests that regular aerobic exercise has limited direct effects on morphine responsiveness, reducing morphine analgesia in males only.

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.

Are endogenous opioid mechanisms involved in the effects of aerobic exercise training on chronic low back pain? A randomized controlled trial.

Aerobic exercise is believed to be an effective chronic low back pain (CLBP) intervention, although its mechanisms remain largely untested. This study evaluated whether endogenous opioid (EO) mechanisms contributed to the analgesic effects of an aerobic exercise intervention for CLBP. Individuals with CLBP were randomized to a 6-week, 18-session aerobic exercise intervention (n = 38) or usual activity control (n = 44). Before and after the intervention, participants underwent separate laboratory sessions to assess responses to evoked heat pain after receiving saline placebo or intravenous naloxone (opioid antagonist) in a double-blinded, crossover fashion. Chronic pain intensity and interference were assessed before and after the intervention. Endogenous opioid analgesia was indexed by naloxone-placebo condition differences in evoked pain responses (blockade effects). Relative to controls, exercise participants reported significantly greater pre-post intervention decreases in chronic pain intensity and interference (Ps < 0.04) and larger reductions in placebo condition evoked pain responsiveness (McGill Pain Questionnaire-Short Form [MPQ]-Total). At the group level, EO analgesia (MPQ-Total blockade effects) increased significantly pre-post intervention only among female exercisers (P = 0.03). Dose-response effects were suggested by a significant positive association in the exercise group between exercise intensity (based on meeting heart rate targets) and EO increases (MPQ-Present Pain Intensity; P = 0.04). Enhanced EO analgesia (MPQ-Total) was associated with a significantly greater improvement in average chronic pain intensity (P = 0.009). Aerobic exercise training in the absence of other interventions appears effective for CLBP management. Aerobic exercise-related enhancements in endogenous pain inhibition, in part EO-related, likely contribute to these benefits.

Physical activity and function in older, long-term colorectal cancer survivors.

OBJECTIVE: Increasing age and cancer history are related to impaired physical function. Since physical activity has been shown to ameliorate age-related functional declines, we evaluated the association between physical activity and function in older, long-term colorectal cancer survivors. METHODS: In 2006-2007, mailed surveys were sent to colorectal cancer survivors, aged > or = 65 years when diagnosed during 1995-2000, and identified through a state cancer registry. Information on physical activity, physical function, and relevant covariates was obtained and matched to registry data. Analysis of covariance and linear regression were used to compare means and trends in physical function across levels of activity in the final analytic sample of 843 cases. RESULTS: A direct, dose-dependent association between physical activity and function was observed (p(trend) < .001), with higher SF-36 physical function subscores in those reporting high versus low activity levels (65.0 +/- 1.7 vs. 42.7 +/- 1.7 (mean +/- standard error)). Walking, gardening, housework, and exercise activities were all independently related to better physical function. Moderate-vigorous intensity activity (p(trend) < .001) was associated with function, but light activity (p(trend) = 0.39) was not. CONCLUSION: Results from this cross-sectional study indicate significant associations between physical activity and physical function in older, long-term colorectal cancer survivors.