Get access

Neurosteroids and Self-Reported Pain in Veterans Who Served in the U.S. Military after September 11, 2001

Authors

  • Jason D. Kilts PhD,

    1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center
    2. Durham Veterans Affairs Medical Center Durham
    3. VA Mid-Atlantic Mental Illness, Research, Education and Clinical Center (Mental Illness Research Education and Clinical Center), Durham
    Search for more papers by this author
  • Larry A. Tupler PhD,

    1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center
    2. Durham Veterans Affairs Medical Center Durham
    3. VA Mid-Atlantic Mental Illness, Research, Education and Clinical Center (Mental Illness Research Education and Clinical Center), Durham
    Search for more papers by this author
  • Francis J. Keefe PhD,

    1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center
    Search for more papers by this author
  • Victoria M. Payne MD MS,

    1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center
    2. Durham Veterans Affairs Medical Center Durham
    3. VA Mid-Atlantic Mental Illness, Research, Education and Clinical Center (Mental Illness Research Education and Clinical Center), Durham
    Search for more papers by this author
  • Robert M. Hamer PhD,

    1. Department of Psychiatry and Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, USA
    Search for more papers by this author
  • Jennifer C. Naylor PhD,

    1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center
    2. Durham Veterans Affairs Medical Center Durham
    3. VA Mid-Atlantic Mental Illness, Research, Education and Clinical Center (Mental Illness Research Education and Clinical Center), Durham
    Search for more papers by this author
  • Rohana P. Calnaido MD,

    1. Durham Veterans Affairs Medical Center Durham
    2. VA Mid-Atlantic Mental Illness, Research, Education and Clinical Center (Mental Illness Research Education and Clinical Center), Durham
    Search for more papers by this author
  • Rajendra A. Morey MD,

    1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center
    2. Durham Veterans Affairs Medical Center Durham
    3. VA Mid-Atlantic Mental Illness, Research, Education and Clinical Center (Mental Illness Research Education and Clinical Center), Durham
    Search for more papers by this author
  • Jennifer L. Strauss PhD,

    1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center
    2. Durham Veterans Affairs Medical Center Durham
    3. VA Mid-Atlantic Mental Illness, Research, Education and Clinical Center (Mental Illness Research Education and Clinical Center), Durham
    Search for more papers by this author
  • Gillian Parke BS,

    1. Durham Veterans Affairs Medical Center Durham
    2. VA Mid-Atlantic Mental Illness, Research, Education and Clinical Center (Mental Illness Research Education and Clinical Center), Durham
    Search for more papers by this author
  • Mark W. Massing MD PhD,

    1. Durham Veterans Affairs Medical Center Durham
    Search for more papers by this author
  • Nagy A. Youssef MD,

    1. Durham Veterans Affairs Medical Center Durham
    2. VA Mid-Atlantic Mental Illness, Research, Education and Clinical Center (Mental Illness Research Education and Clinical Center), Durham
    Search for more papers by this author
  • Lawrence J. Shampine BS,

    1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center
    2. Durham Veterans Affairs Medical Center Durham
    3. VA Mid-Atlantic Mental Illness, Research, Education and Clinical Center (Mental Illness Research Education and Clinical Center), Durham
    Search for more papers by this author
  • the Veterans Affairs Mid-Atlantic Mental Illness, Research, Education and Clinical Center Workgroup,,

    Search for more papers by this author
    • The VA Mid-Atlantic Mental Illness, Research, Education and Clinical Center Workgroup includes Patrick S. Calhoun, PhD, Jean C. Beckham, PhD, Harold S. Kudler, MD, Richard D. Weiner, MD PhD, Gregory McCarthy, PhD, and John A. Fairbank, PhD

  • Christine E. Marx MD MA

    Corresponding author
    1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center
    2. Durham Veterans Affairs Medical Center Durham
    3. VA Mid-Atlantic Mental Illness, Research, Education and Clinical Center (Mental Illness Research Education and Clinical Center), Durham
    Search for more papers by this author

Christine E. Marx, MD MA, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center and Durham VA Medical Center, 508 Fulton Street, Mental Health Service Line (116A), Durham, NC 27705, USA. Tel: 919-286-0411, ext 7426; Fax: 919-286-6811; E-mail: marx0001@mc.duke.edu.

Abstract

Objective.  Nearly half of Operation Enduring Freedom/Operation Iraqi Freedom veterans experience continued pain post-deployment. Several investigations report analgesic effects of allopregnanolone and other neurosteroids in animal models, but few data are currently available focusing on neurosteroids in clinical populations. Allopregnanolone positively modulates GABAA receptors and demonstrates pronounced analgesic and anxiolytic effects in rodents, yet studies examining the relationship between pain and allopregnanolone in humans are limited. We thus hypothesized that endogenous allopregnanolone and other neurosteroid levels may be negatively correlated with self-reported pain symptoms in humans.

Design.  We determined serum neurosteroid levels by gas chromatography/mass spectrometry (allopregnanolone, pregnenolone) or radioimmunoassay (dehydroepiandrosterone [DHEA], progesterone, DHEA sulfate [DHEAS]) in 90 male veterans who served in the U.S. military after September 11, 2001. Self-reported pain symptoms were assessed in four areas (low back pain, chest pain, muscle soreness, headache). Stepwise linear regression analyses were conducted to investigate the relationship between pain assessments and neurosteroids, with the inclusion of smoking, alcohol use, age, and history of traumatic brain injury as covariates.

Setting.  Durham VA Medical Center.

Results.  Allopregnanolone levels were inversely associated with low back pain (P = 0.044) and chest pain (P = 0.013), and DHEA levels were inversely associated with muscle soreness (P = 0.024). DHEAS levels were positively associated with chest pain (P = 0.001). Additionally, there was a positive association between traumatic brain injury and muscle soreness (P = 0.002).

Conclusions.  Neurosteroids may be relevant to the pathophysiology of self-reported pain symptoms in this veteran cohort, and could represent future pharmacological targets for pain disorders.

Ancillary