Salberg Sabrina, Macowan Matthew, Yamakawa Glenn R, Beveridge Jaimie K, Noel Melanie, Marsland Benjamin J, Mychasiuk Richelle
Department of Neuroscience, Monash University, Melbourne, Victoria, Australia.
Department of Immunology and Pathology, Monash University, Melbourne, Victoria, Australia.
Dev Neurobiol. 2023 Jul-Sep;83(5-6):219-233. doi: 10.1002/dneu.22925. Epub 2023 Jul 24.
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.
青少年慢性疼痛是一种日益严重的公共卫生问题。我们对其病因的了解有限；然而，有几个因素会增加易感性，通常是在对诸如外科手术或轻度创伤性脑损伤（mTBI）等急性疼痛触发因素，或童年不良经历（ACE）做出反应时产生。此外，慢性疼痛的患病率和表现存在性别差异，女性的患病率是男性的两倍。尽管如此，大多数临床前疼痛研究都集中在男性身上，这使得我们对女性疼痛机制的理解存在空白。鉴于新出现的证据将肠道微生物群与脑-肠-免疫轴与各种疼痛疾病联系起来，我们旨在研究在ACE和急性损伤作为慢性疼痛触发因素后，肠道微生物群在分类学和功能特征上的性别依赖性变化。将雄性和雌性斯普拉格-道利大鼠幼崽随机分为母婴分离（MS）组或无应激组，然后进一步分为假手术组、mTBI组或手术组。长期来看，使用von Frey试验测量机械性痛觉感受，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增加，同时肠道微生物群也发生了变化。此外，在肠道微生物群组成中发现了显著的性别差异，并且在MS的作用下这种差异更加明显。总体而言，我们提供了初步证据，证明性别差异和ACE诱导的细菌组成变化相结合，可能导致疼痛结果的异质性。
