title: An exploratory pilot investigation of neurosteroids and self-reported pain in female Iraq/Afghanistan-era Veterans.
abstract: Female Veterans are the most rapidly growing segment of new users of the Veterans Health Administration (VHA), and a significant proportion of female Veterans receiving treatment from VHA primary care providers report persistent pain symptoms. Currently, available data characterizing the neurobiological underpinnings of pain disorders are limited. Preclinical data suggest that neurosteroids may be involved in the modulation of pain symptoms, potentially via actions at gamma-aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) receptors. Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) are neurosteroids that modulate inhibitory GABA receptors and excitatory NMDA receptors, producing complex neuronal effects. Emerging evidence from male Iraq/Afghanistan-era Veterans suggests that reductions in neurosteroid levels are associated with increased pain symptoms and that neurosteroids may be promising biomarker candidates. The current exploratory study thus examined associations between self-reported pain symptoms in 403 female Iraq/Afghanistan-era Veterans and serum DHEAS and DHEA levels. Serum DHEAS levels were inversely correlated with low back pain in female Veterans (Spearman r = -0.103; p = 0.04). Nonparametric analyses indicate that female Veterans reporting moderate/extreme low back pain demonstrated significantly lower DHEAS levels than those reporting no/little low back pain (|Z| = 2.60; p = 0.009). These preliminary findings support a role for DHEAS in pain physiology of low back pain and the rationale for neurosteroid therapeutics in pain analgesia.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Naylor
authors.forename: Jason D
authors.initials: JD
authors.lastname: Kilts
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Strauss
authors.forename: Steven T
authors.initials: ST
authors.lastname: Szabo
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Dunn
authors.forename: H Ryan
authors.initials: HR
authors.lastname: Wagner
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hamer
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Shampine
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Zanga
authors.forename: Christine E
authors.initials: CE
authors.lastname: Marx
mesh_terms: D000328:Adult; D055826:Afghan Campaign 2001-; D015415:Biomarkers / Q000097:blood; D003687:Dehydroepiandrosterone / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005260:Female; D006801:Humans; D054542:Iraq War, 2003-2011; D017116:Low Back Pain / Q000097:blood* / Q000503:physiopathology; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000097:blood*; D010865:Pilot Projects; D057566:Self Report; D014728:Veterans
chemical_list: D015415:Biomarkers; D018377:Neurotransmitter Agents; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate
keywords: Afghanistan; DHEA; DHEAS; Iraq; Veteran; back; biomarker; dehydroepiandrosterone; dehydroepiandrosterone sulfate; female; low back pain; neurosteroid; novel; pain; therapeutic