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

Jason D. Kilts, Larry A. Tupler, Francis J. Keefe, Victoria M. Payne, Robert M. Hamer, Jennifer C. Naylor, Rohana P. Calnaido, Rajendra A. Morey, Jennifer L. Strauss, Gillian Parke, Mark W. Massing, Nagy Adel Youssef, Lawrence J. Shampine, Christine E. Marx

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1469-1476
Number of pages8
JournalPain Medicine
Volume11
Issue number10
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

Fingerprint

Pregnanolone
Veterans
Neurotransmitter Agents
Pain
Myalgia
Chest Pain
Dehydroepiandrosterone Sulfate
2003-2011 Iraq War
Dehydroepiandrosterone
Low Back Pain
Analgesics
Afghan Campaign 2001-
Pregnenolone
Somatoform Disorders
Anti-Anxiety Agents
GABA-A Receptors
Pain Measurement
Gas Chromatography-Mass Spectrometry
Radioimmunoassay
Progesterone

Keywords

  • Allopregnanolone
  • DHEA
  • Neuroactive Steroid
  • Neurosteroid
  • Nociception
  • Pain
  • Pregnenolone

ASJC Scopus subject areas

  • Clinical Neurology
  • Anesthesiology and Pain Medicine

Cite this

Kilts, J. D., Tupler, L. A., Keefe, F. J., Payne, V. M., Hamer, R. M., Naylor, J. C., ... Marx, C. E. (2010). Neurosteroids and Self-Reported Pain in Veterans Who Served in the U.S. Military after September 11, 2001. Pain Medicine, 11(10), 1469-1476. https://doi.org/10.1111/j.1526-4637.2010.00927.x

Neurosteroids and Self-Reported Pain in Veterans Who Served in the U.S. Military after September 11, 2001. / Kilts, Jason D.; Tupler, Larry A.; Keefe, Francis J.; Payne, Victoria M.; Hamer, Robert M.; Naylor, Jennifer C.; Calnaido, Rohana P.; Morey, Rajendra A.; Strauss, Jennifer L.; Parke, Gillian; Massing, Mark W.; Youssef, Nagy Adel; Shampine, Lawrence J.; Marx, Christine E.

In: Pain Medicine, Vol. 11, No. 10, 01.01.2010, p. 1469-1476.

Research output: Contribution to journalArticle

Kilts, JD, Tupler, LA, Keefe, FJ, Payne, VM, Hamer, RM, Naylor, JC, Calnaido, RP, Morey, RA, Strauss, JL, Parke, G, Massing, MW, Youssef, NA, Shampine, LJ & Marx, CE 2010, 'Neurosteroids and Self-Reported Pain in Veterans Who Served in the U.S. Military after September 11, 2001', Pain Medicine, vol. 11, no. 10, pp. 1469-1476. https://doi.org/10.1111/j.1526-4637.2010.00927.x
Kilts, Jason D. ; Tupler, Larry A. ; Keefe, Francis J. ; Payne, Victoria M. ; Hamer, Robert M. ; Naylor, Jennifer C. ; Calnaido, Rohana P. ; Morey, Rajendra A. ; Strauss, Jennifer L. ; Parke, Gillian ; Massing, Mark W. ; Youssef, Nagy Adel ; Shampine, Lawrence J. ; Marx, Christine E. / Neurosteroids and Self-Reported Pain in Veterans Who Served in the U.S. Military after September 11, 2001. In: Pain Medicine. 2010 ; Vol. 11, No. 10. pp. 1469-1476.
@article{dc6fb95400c94478a5d948127ca27d53,
title = "Neurosteroids and Self-Reported Pain in Veterans Who Served in the U.S. Military after September 11, 2001",
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.",
keywords = "Allopregnanolone, DHEA, Neuroactive Steroid, Neurosteroid, Nociception, Pain, Pregnenolone",
author = "Kilts, {Jason D.} and Tupler, {Larry A.} and Keefe, {Francis J.} and Payne, {Victoria M.} and Hamer, {Robert M.} and Naylor, {Jennifer C.} and Calnaido, {Rohana P.} and Morey, {Rajendra A.} and Strauss, {Jennifer L.} and Gillian Parke and Massing, {Mark W.} and Youssef, {Nagy Adel} and Shampine, {Lawrence J.} and Marx, {Christine E.}",
year = "2010",
month = "1",
day = "1",
doi = "10.1111/j.1526-4637.2010.00927.x",
language = "English (US)",
volume = "11",
pages = "1469--1476",
journal = "Pain Medicine",
issn = "1526-2375",
publisher = "Wiley-Blackwell",
number = "10",

}

TY - JOUR

T1 - Neurosteroids and Self-Reported Pain in Veterans Who Served in the U.S. Military after September 11, 2001

AU - Kilts, Jason D.

AU - Tupler, Larry A.

AU - Keefe, Francis J.

AU - Payne, Victoria M.

AU - Hamer, Robert M.

AU - Naylor, Jennifer C.

AU - Calnaido, Rohana P.

AU - Morey, Rajendra A.

AU - Strauss, Jennifer L.

AU - Parke, Gillian

AU - Massing, Mark W.

AU - Youssef, Nagy Adel

AU - Shampine, Lawrence J.

AU - Marx, Christine E.

PY - 2010/1/1

Y1 - 2010/1/1

N2 - 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.

AB - 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.

KW - Allopregnanolone

KW - DHEA

KW - Neuroactive Steroid

KW - Neurosteroid

KW - Nociception

KW - Pain

KW - Pregnenolone

UR - http://www.scopus.com/inward/record.url?scp=77957245229&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957245229&partnerID=8YFLogxK

U2 - 10.1111/j.1526-4637.2010.00927.x

DO - 10.1111/j.1526-4637.2010.00927.x

M3 - Article

VL - 11

SP - 1469

EP - 1476

JO - Pain Medicine

JF - Pain Medicine

SN - 1526-2375

IS - 10

ER -