The N‐methyl‐D‐aspartate receptor (NMDAR) is an important mediator of central sensitization and nociception in the rat spinal dorsal horn. The NMDAR subunits and splice variants determine the properties of the receptor. Understanding the expression of NMDAR subunits in spinal cord during the neonatal development is important as it may have consequences for the process of central sensitization and nociception in later life. In this review, a systematic literature search was conducted using three databases: Medline, Embase, and PubMed. A quality assessment was performed on predetermined entities of bias. Thirteen articles were identified to be relevant. The results show that NMDAR subunits and splice variants are dynamically expressed during postnatal development in the spinal dorsal horn. During the first 2 weeks, the expression of less excitable GluN2A subunit and more sensitive GluN2B subunit increases while the expression of high excitable GluN2C subunit decreases. During the 2nd week of postnatal development GluN1 subunits with exon 21 spliced in but exon 22 spliced out are predominantly expressed, increasing phosphorylation, and transport to the membrane. The data suggest that in rats, the nociceptive system is most susceptible to central sensitization processes during the first two postnatal weeks. This may have important consequences for nociception and pain responses in later life. From this, we conclude that targeted therapy directed toward specific NMDAR subunits is a promising candidate for mechanism‐based treatment of pain in neonates.

中文翻译：

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出生后发育过程中大鼠脊髓中 N-甲基-D-天冬氨酸受体表达的定性评价：对中枢敏化和疼痛的影响

N-甲基-D-天冬氨酸受体（NMDAR）是大鼠脊髓背角中枢敏化和伤害感受的重要介质。NMDAR 亚基和剪接变体决定了受体的特性。了解新生儿发育过程中脊髓中 NMDAR 亚基的表达很重要，因为它可能对晚年的中枢敏化和伤害感受过程产生影响。在这篇综述中，使用三个数据库进行了系统的文献检索：Medline、Embase 和 PubMed。对预先确定的偏见实体进行了质量评估。确定有 13 篇文章是相关的。结果表明，NMDAR 亚基和剪接变体在脊髓背角的出生后发育过程中动态表达。在最初的 2 周内，低兴奋性GluN2A亚基和更敏感GluN2B亚基的表达增加，而高兴奋性GluN2C亚基的表达降低。在出生后发育的第 2 周，外显子 21 剪接但外显子 22 剪接出的 GluN1 亚基主要表达，增加磷酸化并转运至膜。数据表明，在大鼠中，伤害感受系统在出生后的前两周最容易受到中枢敏化过程的影响。这可能对以后生活中的伤害感受和疼痛反应产生重要影响。由此，我们得出结论，针对特定 NMDAR 亚基的靶向治疗是基于机制的新生儿疼痛治疗的有希望的候选者。