Study Objective: Pain management in emergency department (ED) patients is challenging. Although both pharmacological and nonpharmacological therapies exist, they are often suboptimal. Immersive virtual reality (VR) uses distraction and possible other methods to reduce perceptions of pain. The purpose of the study is to evaluate the usability and acceptability of VR applications in ED patients by assessing patientreported changes in pain, anger, and anxiety levels. Methods: This is a prospective cohort study at a single academic urban tertiary care center among ED patients with a pain score ‡3 on a numeric rating scale (0-10 integers) for any reason. Patients with stroke, epilepsy, dementia, or other diseases that may prevent use of VR were excluded. Enrolled patients in the intervention cohort spent 20 min using VR applications. A paired t test was used to analyze the change of pain, anger, and anxiety scores between pre-and postintervention. Analysis of variance and linear regression were used to assess the impact of other subject variables (including gender, age, race, and education) on pre-post intervention changes. Results: One hundred (N = 100) patients were enrolled in this study and 93 experienced the VR intervention. Of these, 57 (61.3%) were women, and mean age was 38 -14. Mean anger (2.28 -0.8 to 1.92 -0.7, p < 0.0001), anxiety (2.06 -0.8 to 1.81 -0.8, p < 0.0001), and pain (7.16 -2.5 to 6.49 -2.7, p < 0.0001) levels dropped significantly from pre-to postintervention. Outcomes of the VR intervention were impacted by subject variables, including education and ethnicity. Pain (1.86 -3.3, p = 0.03) and anger (1.03 -1.4, p = 0.02) levels dropped most for those with less than high school education. Linear regression analysis revealed that patients with higher levels of health/quality of life (QOL) had larger mean drop per unit predictor for anger (0.29 [0.09], p = 0.0013) and anxiety (0.22 [0.07], p = 0.001).Conclusions: VR applications are feasible for ED patients and may lead to reduced pain, anger, and anxiety levels. These outcomes are affected by subject ethnicity, educational status, and health/QOL although independent of the chief complaint.

Obesity‐induced hypertension is characterized by a low‐grade inflammatory state along with elevations in circulating long‐chain fatty acids (LCFA). LCFA have been associated with the development of hypertension, although the precise mechanisms remain incompletely defined. Importantly, toll‐like receptor 4 (TLR4) is a transmembrane receptor that is activated by LCFA, resulting in downstream inflammatory cellular processes. The central nervous system (CNS) is critical for the control of blood pressure, with the circumventricular subfornical (SFO) organ playing a critical role. However, the contribution of CNS TLR4 in blood pressure regulation, particularly within the SFO, remains unclear. As a first step, we hypothesized that an SFO LCFA‐TLR4‐inflammatory pathway is associated with elevations in blood pressure. Adult male C57B1/6 mice were instrumented with radiotelemeters for the measurement of blood pressure and implanted with an intracerebroventricular (ICV) cannula. Following recovery, a LCFA (oleic acid, 30 nmol), or vehicle control, was administered once a day over 2 days. Whereas mean arterial blood pressure was unchanged over the course of the study in control animals, 2‐day infusion of LCFA resulted in a pro‐hypertensive response (day 2: 95±2 vs. 110±2 mmHg, ICV vehicle vs. ICV LCFA, p<0.05, n=4). Interestingly, real‐time quantitative PCR analysis revealed SFO TLR4 mRNA upregulation following central LCFA administration when compared to vehicle (1.1±0.3 vs. 2.3±0.4 fold ICV vehicle, ICV vehicle vs. ICV LCFA, p<0.05, n=4). In contrast, TLR4 transcript in the paraventricular nucleus of hypothalamus, another cardioregulatory region, was not different between groups (1.1±0.2 vs. 1.4±0.3 fold ICV vehicle, ICV vehicle vs. ICV LCFA, p>0.05, n=4). Based on this, we further evaluated TLR4 protein expression in the SFO using immunohistochemical analyses. TLR4‐expressing cells were found predominately within the medial to caudal regions of the SFO. Interestingly, co‐immunolabeling indicated that SFO TLR4‐expressing cells were exclusively microglia (Iba1 colocalization: 75±4% TLR4 cells, n=3), whereas no co‐expression was found on astrocytes (GFAP) or neurons (NeuN). Given that TLR4 activation results in the downstream activation of the inflammatory transcription factor NFkB, we subsequently assessed LCFA‐TLR4 mediated activation of NFkB in the SFO using an in vivo bioluminescence imaging technique. In preliminary experiments (n=2), male C57B1/6 mice underwent SFO‐targeted injection of an adenovirus encoding firefly luciferase downstream of the NFκB consensus sequence; this approach allows for imaging of SFO NFκB activity in the same animal over time. When compared to basal levels, two day ICV LCFA administration resulted in an elevation in SFO NF‐κB activity that was evident within 24 hrs (1.3±0.2 fold baseline) and maintained at 48 hrs (1.3±0.4 fold baseline). Taken together, these findings indicate that LCFAs act within the CNS to elicit increases in arterial blood pressure. Moreover, the hypertensive actions of LCFA are paralleled by TLR4 upregulation and NFκB activation in the SFO, suggesting that a LCFA‐TLR4‐NFκB network in this nucleus may contribute to the development of hypertension, such as during obesity.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.