Department of Anesthesia, Division of Pain Management, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Cell Rep. 2024 May 28;43(5):114129. doi: 10.1016/j.celrep.2024.114129. Epub 2024 Apr 18.
The developing peripheral nervous and immune systems are functionally distinct from those of adults. These systems are vulnerable to early-life injury, which influences outcomes related to nociception following subsequent injury later in life (i.e., "neonatal nociceptive priming"). The underpinnings of this phenomenon are unclear, although previous work indicates that macrophages are trained by inflammation and injury. Our findings show that macrophages are both necessary and partially sufficient to drive neonatal nociceptive priming, possibly due to a long-lasting remodeling in chromatin structure. The p75 neurotrophic factor receptor is an important effector in regulating neonatal nociceptive priming through modulation of the inflammatory profile of rodent and human macrophages. This "pain memory" is long lasting in females and can be transferred to a naive host to alter sex-specific pain-related behaviors. This study reveals a mechanism by which acute, neonatal post-surgical pain drives a peripheral immune-related predisposition to persistent pain following a subsequent injury.
发育中的周围神经系统和免疫系统在功能上与成人不同。这些系统容易受到生命早期损伤的影响，这会影响到以后生活中后续损伤相关的痛觉（即“新生儿痛觉致敏”）。尽管之前的研究表明，巨噬细胞可以通过炎症和损伤进行“训练”，但这种现象的基础尚不清楚。我们的研究结果表明，巨噬细胞是驱动新生儿痛觉致敏所必需的，并且在一定程度上是充分的，这可能是由于染色质结构的持久重塑。p75 神经营养因子受体是调节新生儿痛觉致敏的重要效应因子，通过调节啮齿动物和人类巨噬细胞的炎症特征。这种“疼痛记忆”在女性中持续时间较长，并且可以转移到一个幼稚的宿主身上，改变与性别相关的疼痛相关行为。这项研究揭示了一种机制，即急性、新生儿手术后疼痛会导致周围免疫相关的易感性，从而导致随后的损伤后持续疼痛。
