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

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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