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

背景资料：本研究的目的是使用大鼠切口损伤模型，确定与成人相比新生儿术后疼痛的机制。方法：脊髓背角宽动态范围（WDR）和高阈值（HT）神经元的单一活动，这些神经元在后爪足底表面具有感受野（RF），在氨基甲酸乙酯麻醉下从新生大鼠（出生后1-14天）和成年大鼠（8-10周龄）分离。在RF中心通过皮肤、筋膜和肌肉分别为新生儿和成人制作2-5 mm长的切口和1 cm长的切口。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）在切开前和切开后1小时进行评估。在新生大鼠和成年大鼠的一些WDR神经元中，切开后，给予受体拮抗剂AP 5（50 mM）和MK-801（50 mM）以及非NMDA受体拮抗剂CNQX（10 mM） ...更多信息 结果：新生大鼠WDR神经元对4 g和15 g von Frey丝刺激的反应明显大于成年大鼠。P1-P7和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。新生大鼠的WDR神经元在短暂的伤害性刺激后常表现出延长的后放电。随后的自发活动的WDR切口后持续了较长的时间在新生大鼠比成年大鼠切口后。与切割前相比，切割后新生大鼠和成年大鼠WDR神经元对非伤害性和伤害性刺激的反应均明显增加（P < 0.01）。新生大鼠中80%的HT神经元在切口后开始对非伤害性刺激产生反应，而成年大鼠中HT神经元在切口后对非伤害性刺激无反应。当AP 5和MK-801应用于脊髓新生儿WDR神经元1小时后，切口已作出，增加的反应，非伤害性和伤害性刺激几乎完全取消。然而，AP 5和MK-801并没有显着降低WDR神经元的增加反应，非伤害性或伤害性刺激后，成年大鼠的切口。CNQX的应用也取消了WDR神经元对机械刺激的反应后，切口已作出。结论：这些结果表明，新生儿术后疼痛的机制不同于成人，可能取决于不同的兴奋性突触传递通过NMDA受体在脊髓。少

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