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
Francis Joseph Keefe
I am Director of the Duke Pain Prevention and Treatment Research Program, an active NIH funded clinical research program focused on developing new and more effective ways of assessing and treating patients having acute and persistent pain. I have been active in nationally and internationally in shaping the pain research agenda. For the past 10 years I served as Editor in Chief of PAIN the premier journal in pain research. I also have served as the Chair of a number of NIH Study Sections. Finally, I was a member of the Institute of Medicine committee that published a report in 2011 (Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research) that has played a key role in shaping national policies in pain research and pain care.
Over my career, I have played a key role in the development of clinical pain services and pain research programs at Duke Medical Center. For over 20 years, I directed the Duke Pain Management Program and was a leader in the development of Duke Medical Center's multidisciplinary pain programs (both out-patient and in-patient.) I collaborate actively with investigators in other countries (e.g. United Kingdom, South Africa, China, and Australia).
Over the course of my career, I have collaborated closely with investigators both in and outside my lab. Together we have developed and refined a number of treatment protocols for persistent pain conditions (e.g. pain in patients with advanced cancer; sickle cell disease, and persistent joint pain due to osteo- and rheumatoid arthritis) including partner and caregiver-assisted pain coping skills training interventions. We have conducted a number of NIH- and foundation- funded randomized clinical trials testing the efficacy of these and other behavioral interventions (e.g. aerobic exercise protocols, yoga based interventions, mindfulness-based interventions, forgiveness-based interventions, loving kindness meditation, and emotional disclosure).
I currently serve as a Co-Investigator on a number of NIH grants, a number of which are funded by the HEAL Initiative. Many of these grants are testing novel strategies for delivering training in pain coping skills (e.g. video over internet, web-based training, virtual reality interventions, and apps for mobile devices). Along these lines, I collaborated with Dr. Chris Rini to develop an internet-based program for training in pain coping skills called painTRAINER (available at mypaintrainer.org). This program is free to any individuals or health professionals who wish to use it. I have a keen interest in exploring the efficacy of these and other strategies (e.g. training physical therapists, social workers, and nurses) promise to increase access to behavioral pain management interventions making them more widely available to the large population of patients and caregivers who might benefit from them.I have published over 490 papers on topics ranging from pain coping strategies used during mammography to behavioral approaches to managing acute pain and pain at end of life. I have a longstanding interest in mentoring students and early career professionals interested in developing, testing, and disseminating novel protocols for managing pain, stress, and medical symptoms.
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
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.