Chien Chih-Cheng, Fu Wen-Mei, Huang Hsing-I, Lai Yeur-Hur, Tsai Yun-Fang, Guo Shu-Lin, Wu Tzong-Jeng, Ling Qing-Dong
Department of Medicine, School of Medicine, Fu Jen Catholic University, Taipei, Taiwan.
J Pain. 2007 Feb;8(2):161-7. doi: 10.1016/j.jpain.2006.07.004. Epub 2006 Sep 28.
Neonatal peripheral inflammatory insult might result in the alteration of neuronal development in the nociceptive circuit. During early postnatal period, neurotrophins play important roles in neural development and sensory nerve innervation in the central and peripheral nervous systems. In this study, we investigated mRNA expression for neurotrophic factors and their receptors in the dorsal root ganglia of rat pups during postnatal life after peripheral inflammation induced by injection of complete Freund's adjuvant (CFA) into hind paw on postnatal day 1. Our results showed that mRNA expression levels of alpha-calcitonin gene-related peptides, tropomyosin-related kinase-A (trkA), p75 neurotrophin receptor (p75(NTR)), and brain-derived neurotrophic factor (BDNF) elevated significantly after CFA treatment. Such an increase began 1 day after CFA treatment and lasted 2 to 3 days for trkA, p75(NTR), and BDNF. In contrast, there was no change in mRNA expression levels for neurotrophin-4/5, beta-nerve growth factor (beta-NGF), trkB, glial cell line-derived neurotrophin factor, and receptor protein tyrosine kinase protein. Our study demonstrated that neonatal peripheral inflammatory insult might result in molecular changes of neurotrophic factors, particularly in NGF receptors and BDNF, in the process of neuronal development and plasticity in primary afferents during early neonatal period.
Neonatal peripheral inflammation model has been used for the exploration of neuropathic pain mechanism for years. This work provided further detailed information about possible neurotransmitters and peptides involved in this process. This might also lead to future clinical application.
新生儿外周炎症性损伤可能导致伤害性感受回路中神经元发育的改变。在出生后早期,神经营养因子在中枢和外周神经系统的神经发育和感觉神经支配中发挥重要作用。在本研究中,我们研究了在出生后第1天将完全弗氏佐剂(CFA)注射到后爪诱导外周炎症后,新生大鼠背根神经节中神经营养因子及其受体的mRNA表达。我们的结果表明,CFA处理后,α-降钙素基因相关肽、原肌球蛋白相关激酶-A(trkA)、p75神经营养因子受体(p75(NTR))和脑源性神经营养因子(BDNF)的mRNA表达水平显著升高。这种增加在CFA处理后1天开始,trkA、p75(NTR)和BDNF持续2至3天。相比之下,神经营养因子-4/5、β-神经生长因子(β-NGF)、trkB、胶质细胞系源性神经营养因子和受体蛋白酪氨酸激酶蛋白的mRNA表达水平没有变化。我们的研究表明,新生儿外周炎症性损伤可能在新生儿早期初级传入神经元的神经发育和可塑性过程中导致神经营养因子的分子变化,特别是在NGF受体和BDNF中。
新生儿外周炎症模型多年来一直用于探索神经性疼痛机制。这项工作提供了关于参与这一过程的可能神经递质和肽的进一步详细信息。这也可能导致未来的临床应用。