Adolescent chronic pain is a growing public health epidemic. Our understanding of its etiology is limited; however, several factors can increase susceptibility, often developing in response to an acute pain trigger such as a surgical procedure or mild traumatic brain injury (mTBI), or an adverse childhood experience (ACE). Additionally, the prevalence and manifestation of chronic pain is sexually dimorphic, with double the rates in females than males. Despite this, the majority of pre-clinical pain research focuses on males, leaving a gap in mechanistic understanding for females. Given that emerging evidence has linked the gut microbiome and the brain–gut–immune axis to various pain disorders, we aimed to investigate sex-dependent changes in taxonomic and functional gut microbiome features following an ACE and acute injury as chronic pain triggers. Male and female Sprague Dawley rat pups were randomly assigned to either a maternal separation (MS) or no stress paradigm, then further into a sham, mTBI, or surgery condition. Chronically, the von Frey test was used to measure mechanical nociception, and fecal samples were collected for 16S rRNA sequencing. Animals in the surgery group had an increase in pain sensitivity when compared to mTBI and sham groups, and this was complemented by changes to the gut microbiome. In addition, significant sex differences were identified in gut microbiome composition, which were exacerbated in response to MS. Overall, we provide preliminary evidence for sex differences and ACE-induced changes in bacterial composition that, when combined, may be contributing to heterogeneity in pain outcomes.

中文翻译：

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肠道本能：肠道微生物组的性别差异与大鼠母体分离后青少年伤害感受的变化有关

青少年慢性疼痛是一种日益严重的公共卫生流行病。我们对其病因的了解是有限的；然而，有几个因素会增加敏感性，通常是由于急性疼痛触发因素而发生，例如外科手术或轻度创伤性脑损伤 (mTBI)，或不良的童年经历 (ACE)。此外，慢性疼痛的患病率和表现具有性别二态性，女性的发病率是男性的两倍。尽管如此，大多数临床前疼痛研究都集中在男性，而对女性的机制理解存在差距。鉴于新出现的证据已将肠道微生物组和脑-肠-免疫轴与各种疼痛疾病联系起来，我们的目的是研究 ACE 和急性损伤作为慢性疼痛触发因素后，分类学和功能性肠道微生物组特征的性别依赖性变化。雄性和雌性斯普拉道利大鼠幼崽被随机分配到母体分离（MS）或无应激模式，然后进一步进入假手术、mTBI 或手术条件。长期以来，冯弗雷试验被用来测量机械伤害感受，并收集粪便样本进行 16S rRNA 测序。与 mTBI 组和假手术组相比，手术组动物的疼痛敏感性有所增加，并且肠道微生物组的变化补充了这一点。此外，肠道微生物组组成存在显着的性别差异，这种差异因多发性硬化症而加剧。总体而言，我们为性别差异和 ACE 引起的细菌组成变化提供了初步证据，这些变化结合起来可能会导致疼痛结果的异质性。