Allopregnanolone Levels Are Inversely Associated with Self-Reported Pain Symptoms in U.S. Iraq and Afghanistan-Era Veterans: Implications for Biomarkers and Therapeutics.
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2016-01
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BACKGROUND AND OBJECTIVES: Pain symptoms are common among Iraq/Afghanistan-era veterans, many of whom continue to experience persistent pain symptoms despite multiple pharmacological interventions. Preclinical data suggest that neurosteroids such as allopregnanolone demonstrate pronounced analgesic properties, and thus represent logical biomarker candidates and therapeutic targets for pain. Allopregnanolone is also a positive GABAA receptor modulator with anxiolytic, anticonvulsant, and neuroprotective actions in rodent models. We previously reported inverse associations between serum allopregnanolone levels and self-reported pain symptom severity in a pilot study of 82 male veterans. METHODS: The current study investigates allopregnanolone levels in a larger cohort of 485 male Iraq/Afghanistan-era veterans to attempt to replicate these initial findings. Pain symptoms were assessed by items from the Symptom Checklist-90-R (SCL-90-R) querying headache, chest pain, muscle soreness, and low back pain over the past 7 days. Allopregnanolone levels were quantified by gas chromatography/mass spectrometry. RESULTS: Associations between pain ratings and allopregnanolone levels were examined with Poisson regression analyses, controlling for age and smoking. Bivariate nonparametric Mann–Whitney analyses examining allopregnanolone levels across high and low levels of pain were also conducted. Allopregnanolone levels were inversely associated with muscle soreness [P = 0.0028], chest pain [P = 0.032], and aggregate total pain (sum of all four pain items) [P = 0.0001]. In the bivariate analyses, allopregnanolone levels were lower in the group reporting high levels of muscle soreness [P = 0.001]. CONCLUSIONS: These findings are generally consistent with our prior pilot study and suggest that allopregnanolone may function as an endogenous analgesic. Thus, exogenous supplementation with allopregnanolone could have therapeutic potential. The characterization of neurosteroid profiles may also have biomarker utility.
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Naylor, Jennifer C, Jason D Kilts, Steven T Szabo, Charlotte E Dunn, Francis J Keefe, Larry A Tupler, Lawrence J Shampine, Rajendra A Morey, et al. (2016). Allopregnanolone Levels Are Inversely Associated with Self-Reported Pain Symptoms in U.S. Iraq and Afghanistan-Era Veterans: Implications for Biomarkers and Therapeutics. Pain Med, 17(1). pp. 25–32. 10.1111/pme.12860 Retrieved from https://hdl.handle.net/10161/10962.
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Scholars@Duke
Jennifer C. Naylor
Jason David Kilts
Rajendra A. Morey
Research in my lab is focused on brain changes associated with posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), and other neuropsychiatric disorders. We apply several advanced methods for understanding brain function including functional MRI, structural MRI, diffusion tensor imaging, and genetic effects.
Jennifer Leigh Strauss
Henry Ryan Wagner
My research career into neurobiology and mental health spans two distinct phases. The first includes doctoral training at the University of New Mexico in psychology and neurobiology with a major area of emphasis in behavioral neurobiology and two minor areas of emphasis in learning and memory and statistics and experimental design. Doctoral training was subsequently supplemented with postdoctoral study in neuropharmacology at Duke University focusing on brain monoamine systems. For the five years subsequent, I continued exploring the mechanisms underlying receptor regulation of brain catecholamine systems within my laboratory at Columbia University. Following a hiatus, I refocused my research interests away from the laboratory and into statistics and experimental design. This included supplementing a minor area of emphasis in statistics acquired during my doctoral training with extensive course work in biometry through the Division of Biometry within the Department of Community and Family Medicine at Duke University. Using this background, I have continued to consult for the last two decades in the statistical design and analysis of a wide variety of research projects within the Division of Translational Neuroscience in the Department of Psychiatry and Behavioral Sciences as part of the Duke University School of Medicine; the numerous projects undertaken during this interval have included - but are not limited to - randomized clinical trials, epidemologic surveys, and a seemingly endless variety of quasi-experimental designs. More recently, I have expanded my duties to include a position as Statistician for the Mental Illness Research, Education, and Clinical Center with the Durham VA Medical Center.
Christine Elizabeth Marx
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