Neurological Effects of Repeated Blast Exposure in Special Operations Personnel.

Exposure to blast overpressure has been a pervasive feature of combat-related injuries. Studies exploring the neurological correlates of repeated low-level blast exposure in career "breachers" demonstrated higher levels of tumor necrosis factor alpha (TNFα) and interleukin (IL)-6 and decreases in IL-10 within brain-derived extracellular vesicles (BDEVs). The current pilot study was initiated in partnership with the U.S. Special Operations Command (USSOCOM) to explore whether neuroinflammation is seen within special operators with prior blast exposure. Data were analyzed from 18 service members (SMs), inclusive of 9 blast-exposed special operators with an extensive career history of repeated blast exposures and 9 controls matched by age and duration of service. Neuroinflammation was assessed utilizing positron emission tomography (PET) imaging with [18F]DPA-714. Serum was acquired to assess inflammatory biomarkers within whole serum and BDEVs. The Blast Exposure Threshold Survey (BETS) was acquired to determine blast history. Both self-report and neurocognitive measures were acquired to assess cognition. Similarity-driven Multi-view Linear Reconstruction (SiMLR) was used for joint analysis of acquired data. Analysis of BDEVs indicated significant positive associations with a generalized blast exposure value (GBEV) derived from the BETS. SiMLR-based analyses of neuroimaging demonstrated exposure-related relationships between GBEV, PET-neuroinflammation, cortical thickness, and volume loss within special operators. Affected brain networks included regions associated with memory retrieval and executive functioning, as well as visual and heteromodal processing. Post hoc assessments of cognitive measures failed to demonstrate significant associations with GBEV. This emerging evidence suggests neuroinflammation may be a key feature of the brain response to blast exposure over a career in operational personnel. The common thread of neuroinflammation observed in blast-exposed populations requires further study.

Biological function of Extracellular Vesicles (EVs): a review of the field.

Extracellular vesicles (EVs) theranostic potential is under intense investigation. There is a wealth of information highlighting the role that EVs and the secretome play in disease and how these are being utilized for clinical trials and novel therapeutic possibilities. However, understanding of the physiological and pathological roles of EVs remain incomplete. The challenge lies in reaching a consensus concerning standardized quality-controlled isolation, storage, and sample preparation parameters. Interest in circulating EV cargo as diagnostic and prognostic biomarkers is steadily growing. Though promising, various limitations need to be addressed before there can be successful, full-scale therapeutic use of approved EVs. These limitations include obtaining or manufacturing from the appropriate medium (e.g., from bodily fluid or cell culture), loading and isolating EVs, stability, and storage, standardization of processing, and determining potency. This review highlights specific topics, including circulation of abnormal EVs contribute to human disease and the theranostic potential of EVs. Theranostics is defined as a combination of the word's therapeutics and diagnostics and describes how a specific medicine or technique can function as both. Key findings include, (1) EVs and the secretome are future theranostics which will be utilized as both biomarkers for diagnosis and as therapeutics, (2) basic and translational research supports clinical trials utilizing EVs/secretome, and (3) additional investigation is required to fully unmask the theranostic potential of EVs/secretome in specific diseases and injuries.

A Review of Adjunctive Therapies for Burn Injury Pain During the Opioid Crisis.

Opioids are the mainstay of pain management after burn injury. The United States currently faces an epidemic of opioid overuse and abuse, while simultaneously experiencing a nationwide shortage of intravenous narcotics. Adjunctive pain management therapies must be sought and utilized to reduce the use of opioids in burn care to prevent the long-term negative effects of these medications and to minimize the dependence on opioids for analgesia. The purpose of this review was to identify literature on adjunctive pain management therapies that have been demonstrated to reduce pain severity or opioid consumption in adult burn patients. Three databases were searched for prospective studies, randomized controlled trials, and systematic reviews that evaluated adjunctive pain management strategies published between 2008 and 2019 in adult burn patients. Forty-six studies were analyzed, including 24 randomized controlled trials, six crossover trials, and 10 systematic reviews. Various adjunctive pain management therapies showed statistically significant reduction in pain severity. Only one randomized controlled trial on music therapy for acute background pain showed a reduction in opioid use. One cohort study on hypnosis demonstrated reduced opioid use compared with historical controls. We recommend the development of individualized analgesic regimens with the incorporation of adjunctive therapies in order to improve burn pain management in the midst of an abuse crisis and concomitant national opioid shortage.

Does Pain Affect Preference? The Effect of Tonic Laboratory Pain on Discounting of Delayed Rewards.

Chronic pain patients show elevated risk behavior on decision-making tasks, as well as increased health risk behaviors (eg, smoking, prescription opioid abuse). Determining pain's effect on underlying cognitive processes that are associated with risk behavior is confounded by comorbidities linked with chronic pain, including depression, anxiety, and substance abuse. Therefore, to understand pain's effect on delay discounting, a behavioral process assessing the extent to which outcomes are devalued as a function of their delay, the present study evaluated the effect of laboratory pain on delay discounting in healthy young adults (N = 85). Using a mixed factorial design, pain (topical capsaicin and warmth) as well as active control (warmth) groups completed a delay discounting task before and during exposure to their respective manipulations. Whereas the pain condition had no effect on delay discounting, participants' pain intensity, unpleasantness, and pain-induced negative valence were associated with less discounting of delayed rewards. However, the effects were very small. PERSPECTIVE: The results suggest that experimental pain may not increase delay discounting, rather sensitivity to pain predicts a very small decrease in discounting of delayed rewards. Although the results are limited to healthy volunteers, this experimental approach allows us to examine the relationship between pain and delay discounting in a controlled manner. Better understanding of pain-related decision-making may lead to improved treatment of health risk behaviors for individuals experiencing pain.