There is a need for non-invasive biomarkers and novel therapies for combat persistent injuries, including injury-induced inflammation and pain as well as the combat stress reaction (CSR). Service Members are exposed to adversarial conditions that can result in sustained combat injuries. Therefore, a major research goal is to understand the mechanisms that underlie these injuries to identify and test novel therapeutics. Inflammation and pain is experienced as a result of all combat-related injuries and can be exacerbated by physical and psychological stress. The combat stress reaction (CSR), experienced as a direct result of battlefield stress exposure, exhibits as a collection of autonomic nervous system symptoms, such as exhaustion, that function to limit the Service Member’s performance. In extreme hostile conditions, the ratio can be as high as 1:1 for CSR to battle casualties. Currently, knowledge pertaining to biomarkers for inflammation, CSR, pain development, and other combat-related injuries is severely lacking. In this special issue, we explore extracellular vesicular (EV) content as biomarkers and therapies of combat-related morbidities. This research is also quite applicable to civilian-sustained injuries.

EV contained content are attractive biomarker candidates due to their conservation across species, stability in liquid biopsies, and variation that corresponds to a pathologic state. miRNA, mRNA, and protein can be sorted into EVs within the cell and released from a site of injury followed by endocytosis by adjacent or distant target cells. Upon uptake, the EV content can function to affect various signaling pathways that may contribute to inflammation, pain, CSR, or other combat-related morbidities. Previously, we discovered several potential biomarkers of nerve injury and for the development of neuropathic pain. The focus of this previous study was to determine the plasma derived EV miRNA content in a neuropathic pain model (Sosanya et al., 2019, J Pain). In this proposed special issue, we explore research in the use of EV content as biomarkers and therapies for inflammation, pain, CSR, and other combat-related morbidities.

Aims and Scope: