scholarly journals Development of KVO treatment strategies for chronic pain in a rat model of Gulf War Illness

Author(s):  
L.D. Flunker ◽  
T.J. Nutter ◽  
C.M. Bowers ◽  
B.Y. Cooper
2021 ◽  
Vol 22 (16) ◽  
pp. 8546
Author(s):  
Francisco J. Carrera Arias ◽  
Kristina Aenlle ◽  
Maria Abreu ◽  
Mary A. Holschbach ◽  
Lindsay T. Michalovicz ◽  
...  

Gulf War Illness (GWI) is a persistent chronic neuroinflammatory illness exacerbated by external stressors and characterized by fatigue, musculoskeletal pain, cognitive, and neurological problems linked to underlying immunological dysfunction for which there is no known treatment. As the immune system and the brain communicate through several signaling pathways, including the hypothalamic–pituitary–adrenal (HPA) axis, it underlies many of the behavioral and physiological responses to stressors via blood-borne mediators, such as cytokines, chemokines, and hormones. Signaling by these molecules is mediated by the semipermeable blood–brain barrier (BBB) made up of a monocellular layer forming an integral part of the neuroimmune axis. BBB permeability can be altered and even diminished by both external factors (e.g., chemical agents) and internal conditions (e.g., acute or chronic stress, or cross-signaling from the hypothalamic–pituitary–gonadal (HPG) axis). Such a complex network of regulatory interactions that possess feed-forward and feedback connections can have multiple response dynamics that may include several stable homeostatic states beyond normal health. Here we compare immune and hormone measures in the blood of human clinical samples and mouse models of Gulf War Illness (GWI) subtyped by exposure to traumatic stress for subtyping this complex illness. We do this via constructing a detailed logic model of HPA–HPG–Immune regulatory behavior that also considers signaling pathways across the BBB to neuronal–glial interactions within the brain. We apply conditional interactions to model the effects of changes in BBB permeability. Several stable states are identified in the system beyond typical health. Following alignment of the human and mouse blood profiles in the context of the model, mouse brain sample measures were used to infer the neuroinflammatory state in human GWI and perform treatment simulations using a genetic algorithm to optimize the Monte Carlo simulations of the putative treatment strategies aimed at returning the ill system back to health. We identify several ideal multi-intervention strategies and potential drug candidates that may be used to treat chronic neuroinflammation in GWI.


2018 ◽  
Vol 67 ◽  
pp. 42-46 ◽  
Author(s):  
Bang-Bon Koo ◽  
Lindsay T. Michalovicz ◽  
Samantha Calderazzo ◽  
Kimberly A. Kelly ◽  
Kimberly Sullivan ◽  
...  

2020 ◽  
Vol 12 ◽  
pp. 100210 ◽  
Author(s):  
V.A. Macht ◽  
J.L. Woodruff ◽  
H.E. Burzynski ◽  
C.A. Grillo ◽  
L.P. Reagan ◽  
...  

Life Sciences ◽  
2021 ◽  
pp. 119867
Author(s):  
Huy Nguyen ◽  
Peyman Sahbaie ◽  
Lihle Goba ◽  
Julian Sul ◽  
Aoi Suzaki ◽  
...  

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1211-1211
Author(s):  
Kathleen Holton ◽  
Anna Kirkland ◽  
Elizabeth Brandley ◽  
John VanMeter ◽  
James Baraniuk

Abstract Objectives The objective was to examine if a low glutamate diet can reduce symptoms in Gulf War Illness (GWI), a multi-symptom chronic pain condition. Methods Forty GW veterans were recruited from across the US. Baseline measures included assessment of symptoms, myalgic score, tender point count, and dolorimetry. Subjects were randomized to the low glutamate diet, or to a wait-listed control group, starting the diet one month later. Measures were evaluated post-diet, and then subjects were randomized to a double-blind placebo-controlled crossover challenge with monosodium glutamate (MSG)/placebo to assess whether symptoms return/worsen in each condition. Challenge data have not yet been un-blinded, and thus are not included in this abstract. Symptom scores were compared between those randomized to immediate dietary intervention versus wait-listed controls (independent t-tests). After everyone completed the 1-month diet, change scores were analyzed for the whole group (Wilcoxon Signed Rank tests). Improvement was defined as ‘much’ or ‘very much’ improved on the patient global impression of change (PGIC) score, and the effect size was calculated (Cohen's d). Results After 1-month, overall symptom number (mean (SD)) significantly differed between the diet group (11(6)) and the wait-listed controls (18(6)), P = 0.0007. The diet had a very large effect size, d = 1.17, with no adverse effects reported. When comparing pre-post scores after all subjects followed the 1-month diet, the number of symptoms went from a mean(SD) of 21(5) at baseline to 12(6) post-diet, P < 0.0001. The severity of remaining symptoms was also significantly reduced (all P < 0.0001). Seventy-two % of subjects met the PGIC criteria for improvement. Highly significant improvements in pain measures were also observed for myalgic score (P < 0.0001), number of tender points (P < 0.0001), and average dolorimetry (P < 0.001). Conclusions These striking results suggest that the low glutamate diet may be an effective treatment for chronic pain and symptoms associated with Gulf War Illness. Funding Sources Department of Defense (DoD), US Army Medical Research Acquisition Activity, Office of the Assistant Secretary of Defense for Health Affairs through the GWI Research Program. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the DoD.


2020 ◽  
Vol 80 ◽  
pp. 52-59 ◽  
Author(s):  
Ana C.R. Ribeiro ◽  
Jackie Zhu ◽  
Mohamad M. Kronfol ◽  
Fay M. Jahr ◽  
Rabha M. Younis ◽  
...  

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