TY - JOUR T1 - The Dynorphin/Kappa Opioid Receptor mediates adverse immunological and behavioral outcomes induced by repetitive blast trauma in male mice JF - bioRxiv DO - 10.1101/2022.08.15.504055 SP - 2022.08.15.504055 AU - Suhjung Janet Lee AU - Aric F. Logsdon AU - Mayumi Yagi AU - Britahny M. Baskin AU - Elaine. R. Peskind AU - Murray M. Raskind AU - David G. Cook AU - Abigail. G. Schindler Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/08/15/2022.08.15.504055.abstract N2 - Background Adverse pathophysiological and behavioral outcomes related to mild traumatic brain injury (mTBI), posttraumatic stress disorder (PTSD), and chronic pain are common following blast exposure and contribute to decreased quality of life, but underlying mechanisms and prophylactic/treatment options remain limited. The dynorphin/kappa opioid receptor (KOR) system helps regulate behavioral and inflammatory responses to stress and injury; however, it has yet to be investigated as a potential mechanism in either humans or animals exposed to blast. We hypothesized that blast-induced KOR activation mediates adverse outcomes related to inflammation and affective behavioral response.Methods C57Bl/6 adult male mice were singly or repeatedly exposed to either sham (anesthesia only) or blast delivered by a pneumatic shock tube. The selective KOR antagonist norBNI or vehicle (saline) was administered 72 hours prior to repetitive blast or sham exposure. Serum and brain were collected 10 minutes or 4 hours post-exposure for dynorphin and cytokine measurements, respectively. At one-month post-exposure, mice were tested in a series of behavioral assays related to adverse outcomes reported by humans with blast trauma.Results Repetitive but not single blast exposure resulted in increased brain dynorphin level. norBNI pretreatment blocked or significantly reduced blast-induced increase in serum and brain cytokines, including IL-6, at 4 hours post exposure and aversive/anxiety-like behavioral dysfunction at one month post exposure.Conclusions Our findings demonstrate a previously unreported role for the dynorphin/KOR system as a mediator of biochemical and behavioral dysfunction following repetitive blast exposure and highlight this system as a potential prophylactic/therapeutic treatment target.Competing Interest StatementThe authors have declared no competing interest. ER -