Nandi R, Fitzgerald M
Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
Eur J Pain. 2005 Apr;9(2):105-8. doi: 10.1016/j.ejpain.2004.05.005.
Pain in neonates is now well established. Studies of the developmental neurobiology of pain have revealed that pain processing in the immature is very different from that in the mature nervous system. Neonates undergo considerable maturation of peripheral, spinal and supraspinal afferent pain transmission over the early postnatal period but are able to respond to tissue injury with specific behaviour and with autonomic, hormonal and metabolic signs of stress and distress. Opioid analgesia is now widely used in neonates. There is evidence that morphine requirements may be low in the youngest patients. Sensory threshold testing in rat pups has shown that the analgesic potency of systemic morphine mechanical stimulation is significantly greater in the neonate and declines with postnatal age. The changing morphine sensitivity in the postnatal period may be part of a general reorganisation in the structure and function of primary afferent synapses, neurotransmitter/receptor expression and function and excitatory and inhibitory modulation from higher brain centres. Importantly opioid receptor expression undergoes significant developmental regulation - mu opioid receptors, observed to be exuberantly expressed in the neonatal rat, have been found to be functional. These findings have important implications for the human neonate as they provide a possible explanation for the differences in morphine requirements observed in the youngest patients. The study of the underlying mechanisms of pain and analgesia in development has enabled important changes in clinical practice. However, pain in the newborn remains poorly understood and continued research and intensive study in this area is essential for further effective analgesic intervention and the discovery of new targets for therapy.
新生儿疼痛现已得到充分证实。对疼痛发育神经生物学的研究表明，未成熟个体的疼痛处理与成熟神经系统中的情况截然不同。在出生后的早期阶段，新生儿的外周、脊髓和脊髓上的传入性疼痛传递会经历相当程度的成熟，但他们能够通过特定行为以及自主神经、激素和代谢方面的应激和痛苦迹象对组织损伤做出反应。阿片类镇痛药目前在新生儿中广泛使用。有证据表明，年龄最小的患者对吗啡的需求量可能较低。对幼鼠进行的感觉阈值测试表明，全身性吗啡对机械刺激的镇痛效力在新生儿中显著更高，并随出生后的年龄增长而下降。出生后时期吗啡敏感性的变化可能是初级传入突触的结构和功能、神经递质/受体表达与功能以及来自更高脑区的兴奋性和抑制性调节进行全面重组的一部分。重要的是，阿片受体表达受到显著的发育调控——已观察到μ阿片受体在新生大鼠中大量表达，且已发现其具有功能。这些发现对人类新生儿具有重要意义，因为它们为年龄最小的患者中观察到的吗啡需求量差异提供了一种可能的解释。对发育过程中疼痛和镇痛潜在机制的研究已促使临床实践发生了重要变化。然而，新生儿疼痛仍未得到充分理解，在这一领域持续开展研究和深入探讨对于进一步进行有效的镇痛干预以及发现新的治疗靶点至关重要。
