Dourson Adam J, Fadaka Adewale O, Warshak Anna M, Paranjpe Aditi, Weinhaus Benjamin, Queme Luis F, Hofmann Megan C, Evans Heather M, Donmez Omer A, Forney Carmy, Weirauch Matthew T, Kottyan Leah T, Lucas Daniel, Deepe George S, Jankowski Michael P
bioRxiv. 2023 Dec 14:2023.02.13.528015. doi: 10.1101/2023.02.13.528015.
The developing peripheral nervous and immune systems are functionally distinct from adults. These systems are vulnerable to early life injury, which influences outcomes related to nociception following subsequent injury later in life (neonatal nociceptive priming). The underpinnings of this phenomenon are largely unknown, although previous work indicates that macrophages are epigenetically trained by inflammation and injury. We found that macrophages are both necessary and partially sufficient to drive neonatal nociceptive priming possibly due to a long-lasting epigenetic remodeling. The p75 neurotrophic factor receptor (NTR) was an important effector in regulating neonatal nociceptive priming through modulation of the inflammatory profile of rodent and human macrophages. This pain memory was long lasting in females and could be transferred to a naive host to alter sex-specific pain-related behaviors. This study reveals a novel mechanism by which acute, neonatal post-surgical pain drives a peripheral immune-related predisposition to persistent pain following a subsequent injury.
发育中的外周神经系统和免疫系统在功能上与成人不同。这些系统易受生命早期损伤的影响，这会影响生命后期后续损伤后与伤害感受相关的结果（新生儿伤害感受致敏）。尽管先前的研究表明巨噬细胞会受到炎症和损伤的表观遗传训练，但这种现象的基础在很大程度上尚不清楚。我们发现巨噬细胞对于驱动新生儿伤害感受致敏既是必要的，也是部分充分的，这可能是由于长期的表观遗传重塑。p75神经营养因子受体（NTR）是通过调节啮齿动物和人类巨噬细胞的炎症特征来调节新生儿伤害感受致敏的重要效应器。这种疼痛记忆在雌性中持续时间很长，并且可以转移到未接触过的宿主身上，以改变性别特异性的疼痛相关行为。这项研究揭示了一种新机制，即急性新生儿手术后疼痛会导致外周免疫相关的易感性，使后续损伤后易患持续性疼痛。
