An exploratory pilot investigation of neurosteroids and self-reported pain in female Iraq/Afghanistan-era Veterans.

Jennifer C Naylor, Jason D Kilts, Jennifer L Strauss, Steven T Szabo, Charlotte E Dunn, H Ryan Wagner, Robert M Hamer, Lawrence J Shampine, Joseph R Zanga, Christine E Marx
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引用次数: 8

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.

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伊拉克/阿富汗时期女性退伍军人神经类固醇和自述疼痛的探索性试点调查。
女性退伍军人是退伍军人健康管理局(VHA)新用户中增长最快的部分,而且在接受VHA初级保健提供者治疗的女性退伍军人中,有很大一部分报告了持续的疼痛症状。目前,描述疼痛障碍的神经生物学基础的可用数据是有限的。临床前数据表明,神经类固醇可能参与疼痛症状的调节,可能通过对γ -氨基丁酸(GABA)和n -甲基- d -天冬氨酸(NMDA)受体的作用。脱氢表雄酮(DHEA)和硫酸脱氢表雄酮(DHEAS)是调节抑制性GABA受体和兴奋性NMDA受体的神经类固醇,产生复杂的神经元效应。来自伊拉克/阿富汗时期男性退伍军人的新证据表明,神经类固醇水平的降低与疼痛症状的增加有关,神经类固醇可能是有希望的生物标志物候选者。因此,目前的探索性研究检查了403名伊拉克/阿富汗时期女性退伍军人自我报告的疼痛症状与血清脱氢表雄酮和脱氢表雄酮水平之间的关系。血清DHEAS水平与女性退伍军人腰痛呈负相关(Spearman r = -0.103;P = 0.04)。非参数分析表明,报告中度/极度腰痛的女退伍军人的DHEAS水平显著低于报告无/轻微腰痛的女退伍军人(|Z| = 2.60;P = 0.009)。这些初步研究结果支持DHEAS在腰痛疼痛生理学中的作用,以及神经类固醇治疗疼痛镇痛的基本原理。
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