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Mechanisms of postoperative pain in neonate : analysis using in vivo patch clamp recording from superficial dorsal horn neurons.

新生儿术后疼痛的机制：使用浅表背角神经元体内膜片钳记录进行分析。

基本信息

批准号：
15591646
负责人：
KAWAMATA Mikito
金额：
$ 2.18万
依托单位：
Sapporo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591646/
关键词：
Spinal dorsal horn neonate incision iniur in vivo patch-clamp recording

项目摘要

Background: The aim of the present study was to determine mechanisms of postoperative pain in neonates compared to those in adults, using the incision injury model in rats.Methods: A single activity of spinal dorsal horn wide-dyanamic-range (WDR) and high-threshold (HT) neurons, that had receptive fields (RFs) on the plantar surface of the hindpaw, was isolated from neonatal rats (postnatal days 1-14) and adult rats (8-10 weeks old) under urethane anesthesis. A 2-5 mm-long incision and 1-cm-long incision were made for neonates and for adults, respectively, in the center of the RF through the skin, fascia and muscle. Neuronal activity (spontaneous activity, RF size and responses to non-noxious and noxious stimuli applied on the center of the RF) was assessed before and 1 hr after the incision had been made. In some WDR neurons in neonate and adult rats, after the incision had been made, receptor antagonists, AP5 (50 mM) and MK-801(50 mM), and a non-NMDA receptor antagonist, CNQX (10 mM) … More , were applied into the surface of the spinal cord.Results: Responses of WDR neurons to von Frey filament stimuli (4 g and 15 g) were significantly greater in the neonatal rats than those in the adult rats. There were no significant difference in responses of WDR neurons to non-noxious or noxious stimuli between P1-P7 neonatal rats and P8-P14 neonatal rats. WDR neurons in neonatal rats often showed prolonged after-discharge following brief noxious stimuli. Subsequent spontaneous activity of WDR following incision lasted for a longer period of time in neonate rats than in adult rats after the incision had been made. Responses to non-noxious and noxious stimuli of WDR neurons significantly increased in the neonatal rats and adult rats after the incision (P < 0.01), compared to the pre-incision values. Eighty percent of HT neurons in neonatal rats began to respond to non-noxious stimuli after the incision had been made, whereas HT neurons could not respond to non-noxious stimuli in the adult rats after the incision. When AP5 and MK-801 were applied onto the spinal cord in neonatal WDR neurons 1 hr after the incision had been made, the increased responses to non-noxious and noxious stimuli almost completely abolished. However, AP5 and MK-801 did not significantly reduce the increased responses of WDR neurons to non-noxious or noxious stimuli in adult rats after the incision had been made. Application of CNQX also abolished the responses of WDR neurons to mechanical stimuli after the incision had been made. Conclusions : These findings suggest the mechanisms of postoperative pain in neonates are different from those in adults, possibly depending on the different excitatory synapse transmission through NMDA receptors in the spinal cord. Less

背景：采用大鼠切开损伤模型，比较新生大鼠和成年大鼠术后疼痛的发生机制。方法：在乌拉坦麻醉下，分离新生大鼠(出生后1~14天)和成年大鼠(8~10周龄)足底面具有感受野的脊髓背角宽动态范围(WDR)和高阈值(HT)神经元的单一活动。新生儿和成人分别经皮肤、筋膜和肌肉在RF中央作2~5 mm长和1 cm长的切口。在切开前和切开后1小时检测神经元活动(自发活动、RF大小和对RF中心施加的非伤害性和伤害性刺激的反应)。在新生和成年大鼠的部分WdR神经元上，切开后，受体拮抗剂AP5(50 MM)和MK-801(50 MM)和非NMDA型受体拮抗剂CNQX(10 MM)…结果：新生大鼠WDR神经元对von Frey细丝(4g和15g)刺激的反应明显强于成年大鼠。P1-P7新生大鼠与P8-P14新生大鼠WDR神经元对非伤害性或伤害性刺激的反应无显著差异。新生大鼠WDR神经元在短暂伤害性刺激后常表现出较长的后放电。新生大鼠切开后WDR的自发活动持续时间长于成年大鼠切开后。新生大鼠和成年大鼠切开后对WDR神经元非伤害性和伤害性刺激的反应较切开前显著增加(P&lt；0.01)。新生大鼠有80%的HT神经元在切开后开始对非伤害性刺激有反应，而成年大鼠在切开后不能对非伤害性刺激有反应。切开后1小时，将AP5和MK-801应用于新生WDR神经元的脊髓，对非伤害性刺激和伤害性刺激的增强反应几乎完全消失。然而，AP5和MK-801并不能显著降低成年大鼠WDR神经元对非伤害性或伤害性刺激的反应。应用CNQX后，WDR神经元对机械刺激的反应也完全消失。结论：新生儿术后疼痛机制不同于成人，可能与脊髓NMDA受体介导的兴奋性突触传递不同有关。较少