Allopregnanolone Levels Are Inversely Associated with Self-Reported Pain Symptoms in U.S. Iraq and Afghanistan-Era Veterans: Implications for Biomarkers and Therapeutics.

Naylor, Jennifer C

Kilts, Jason D

Szabo, Steven T

Dunn, Charlotte E

Keefe, Francis J

Tupler, Larry A

Shampine, Lawrence J

Morey, Rajendra A

Strauss, Jennifer L

Hamer, Robert M

Wagner, H Ryan

MIRECC Workgroup

Marx, Christine E

England

2015-12-03T14:52:16Z

2016-01

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.

http://www.ncbi.nlm.nih.gov/pubmed/26176345

1526-4637

https://hdl.handle.net/10161/10962

eng

Oxford University Press (OUP)

Pain Med

10.1111/pme.12860

Adult

Afghan Campaign 2001-

Afghanistan

Biomarkers

Female

Headache

Humans

Iraq

Iraq War, 2003-2011

Male

Middle Aged

Pain

Pregnanolone

Self Report

Stress Disorders, Post-Traumatic

Veterans

Allopregnanolone Levels Are Inversely Associated with Self-Reported Pain Symptoms in U.S. Iraq and Afghanistan-Era Veterans: Implications for Biomarkers and Therapeutics.

Journal article

Keefe, Francis J|0000-0003-0583-9326

Tupler, Larry A|0000-0001-7372-8711

Wagner, H Ryan|0000-0003-3954-6556

http://www.ncbi.nlm.nih.gov/pubmed/26176345

25

32

1

Anesthesiology

Clinical Science Departments

Duke

Duke Cancer Institute

Duke Institute for Brain Sciences

Duke-UNC Center for Brain Imaging and Analysis

Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Medicine, General Internal Medicine

Medicine, Rheumatology and Immunology

Psychiatry, Child & Family Mental Health and Developmental Neuroscience

Psychiatry & Behavioral Sciences

Psychiatry & Behavioral Sciences, Addictions

Psychiatry & Behavioral Sciences, Behavioral Medicine

Psychiatry & Behavioral Sciences, Brain Stimulation and Neurophysiology

Psychiatry & Behavioral Sciences, General Psychiatry

Psychiatry & Behavioral Sciences, Social and Community Psychiatry

Psychiatry & Behavioral Sciences, Translational Neuroscience

Psychology and Neuroscience

School of Medicine

Trinity College of Arts & Sciences

University Institutes and Centers

Published

17