Chronic posttraumatic pain (CPTP) is common after traumatic stress exposure (TSE) and disproportionately burdens women. We previously showed across 3 independent longitudinal cohort studies that, in women, increased peritraumatic 17β-estradiol (E2) levels were associated with substantially lower CPTP over 1 year. Here, we assessed this relationship in a fourth longitudinal cohort and also assessed the relationship between E2 and CPTP at additional time points post-TSE. Furthermore, we used a well-validated animal model of TSE to determine whether exogenous E2 administration protects against mechanical hypersensitivity. Using nested samples and data from the Advancing Understanding of RecOvery afteR traumA study (n = 543 samples, 389 participants), an emergency department-based prospective study of TSE survivors, we assessed the relationship between circulating E2 levels and CPTP in women and men using multivariate repeated-measures mixed modeling. Male and ovariectomized female Sprague Dawley rats were exposed to TSE and administered E2 either immediately after or 3 days post-TSE. Consistent with previous results, we observed an inverse relationship between peritraumatic E2 and longitudinal CPTP in women only (β = -0.137, P = 0.033). In animals, E2 protected against mechanical hypersensitivity in female ovariectomized rats only if administered immediately post-TSE. In conclusion, peritraumatic E2 levels, but not those at post-TSE time points, predict CPTP in women TSE survivors. Administration of E2 immediately post TSE protects against mechanical hypersensitivity in female rats. Together with previous findings, these data indicate that increased peritraumatic E2 levels in women have protective effects against CPTP development and suggest that immediate post-TSE E2 administration in women could be a promising therapeutic strategy for reducing risk of CPTP.

中文翻译：

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来自人类和动物的数据进一步证明，创伤周围 17β-雌二醇水平会影响女性慢性创伤后疼痛的结果。


慢性创伤后疼痛（CPTP）在创伤性应激暴露（TSE）后很常见，给女性带来了不成比例的负担。我们之前的 3 项独立纵向队列研究表明，在女性中，创伤周围 17β-雌二醇 (E2) 水平升高与 1 年内 CPTP 大幅降低相关。在这里，我们在第四个纵向队列中评估了这种关系，并在 TSE 后的其他时间点评估了 E2 和 CPTP 之间的关系。此外，我们使用经过充分验证的 TSE 动物模型来确定外源性 E2 给药是否可以预防机械过敏。使用嵌套样本和来自“Advancing Understanding of RecOvery after traumA”研究（n = 543 个样本，389 名参与者）的数据（一项基于急诊科的 TSE 幸存者前瞻性研究），我们使用以下方法评估了女性和男性的循环 E2 水平与 CPTP 之间的关系：多变量重复测量混合建模。雄性和切除卵巢的雌性 Sprague Dawley 大鼠暴露于 TSE，并在 TSE 后立即或 3 天后施用 E2。与之前的结果一致，我们仅在女性中观察到创伤周围 E2 与纵向 CPTP 之间存在负相关关系（β = -0.137，P = 0.033）。在动物中，只有在 TSE 后立即给药，E2 才能防止雌性卵巢切除大鼠的机械过敏。总之，创伤周围 E2 水平（而非 TSE 后时间点的 E2 水平）可以预测女性 TSE 幸存者的 CPTP。 TSE 后立即给予 E2 可防止雌性大鼠出现机械过敏。 与之前的研究结果一起，这些数据表明，女性创伤周围 E2 水平升高对 CPTP 的发展具有保护作用，并表明女性 TSE 后立即施用 E2 可能是降低 CPTP 风险的一种有前景的治疗策略。