Neonatal colon insult alters growth factor expression and TRPA1 responses in adult mice.
Neonatal colon insult alters growth factor expression and TRPA1 responses in adult mice.
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DOI：
10.1016/j.pain.2010.08.029
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发表时间：
2010-11
期刊：
影响因子：
7.4
通讯作者：
Davis BM
中科院分区：
文献类型：
--
作者：
Christianson JA;Bielefeldt K;Malin SA;Davis BM
新生儿发育期间的炎症或疼痛可导致伤害性通路的长期结构和功能改变，最终改变成年后的疼痛感知。我们建立了一种新生儿结肠刺激（NCI）小鼠模型，以研究内脏感觉系统内疼痛处理的可塑性。小鼠幼崽在出生后第8天和第10天接受2%芥子油（MO）的结肠内给药。在随后的时间点对远端结肠进行髓过氧化物酶（MPO）活性和生长因子表达的处理。通过测量结直肠扩张期间的内脏反应来评估成年小鼠的内脏高敏感性。从远端结肠逆行标记成年小鼠背根神经节（DRG）神经元，并使用钙成像来测量瞬时受体电位香草酸1（TRPV 1）和锚蛋白1（TRPA 1）反应急性应用辣椒素和MO，分别。尽管没有炎症（如MPO活性所示），新生儿暴露于结肠内MO短暂维持较高的生长因子信使RNA（mRNA）的表达水平。与对照小鼠相比，成年NCI小鼠表现出显著的内脏高敏感性，以及对后爪机械刺激的敏感性增加。在NCI小鼠中，表达TRPA1的结肠传入神经的百分比显著增加，但是它们没有显示TRPV1免疫阳性或辣椒素敏感的结肠DRG神经元的百分比增加。这些结果表明，早期新生儿结肠损伤导致长期内脏高敏感性，可能是由生长因子表达的早期增加驱动，并由TRPA 1功能的永久性变化维持。
Inflammation or pain during neonatal development can result in long-term structural and functional alterations of nociceptive pathways, ultimately altering pain perception in adulthood. We have developed a mouse model of neonatal colon irritation (NCI) to investigate the plasticity of pain processing within the viscerosensory system. Mouse pups received an intracolonic administration of 2% mustard oil (MO) on postnatal days 8 and 10. Distal colons were processed at subsequent timepoints for myeloperoxidase (MPO) activity and growth factor expression. Adult mice were assessed for visceral hypersensitivity by measuring the visceromotor response during colorectal distension. Dorsal root ganglion (DRG) neurons from adult mice were retrogradely labeled from the distal colon and calcium imaging was used to measure transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) responses to acute application of capsaicin and MO, respectively. Despite the absence of inflammation (as indicated by MPO activity), neonatal exposure to intracolonic MO transiently maintained a higher expression level of growth factor messenger RNA (mRNA). Adult NCI mice displayed significant visceral hypersensitivity, as well as increased sensitivity to mechanical stimulation of the hindpaw, compared to control mice. The percentage of TRPA1-expressing colon afferents was significantly increased in NCI mice, however they displayed no increase in the percentage of TRPV1-immunopositive or capsaicin-sensitive colon DRG neurons. These results suggest that early neonatal colon injury results in a long-lasting visceral hypersensitivity, possibly driven by an early increase in growth factor expression and maintained by permanent changes in TRPA1 function.
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