Preemptive morphine analgesia attenuates the long-term consequences of neonatal inflammation in male and female rats.
Preemptive morphine analgesia attenuates the long-term consequences of neonatal inflammation in male and female rats.
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DOI：
10.1203/pdr.0b013e31818702d4
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发表时间：
2008-12
影响因子：
3.6
通讯作者：
Murphy, Anne Z.
中科院分区：
文献类型：
--
作者：
Laprairie, Jamie L.;Johns, Malcolm E.;Murphy, Anne Z.
尽管越来越多的证据表明疼痛管理对早产儿至关重要，但镇痛药在这一人群中的临床应用却十分有限。我们之前的研究表明，新生儿炎症会导致成年后躯体感觉阈值发生长期改变，表现为基线伤害感受敏感性降低，以及在后续炎症刺激后痛觉过敏增强。本研究旨在确定预防性使用吗啡是否能减轻这些不良后果。在出生后第0天（P0），幼鼠在足底注射1%角叉菜胶（CGN）前先接受硫酸吗啡（MS）注射。对照组幼鼠分别接受生理盐水（SAL）后再足底注射CGN、MS后再足底注射SAL，或SAL后再足底注射SAL。预防性使用吗啡显著减轻了幼鼠在青春期和成年期由新生儿期损伤诱导的痛觉减退。同样，与对照组相比，经吗啡预处理的动物在后续炎症刺激下痛觉过敏程度明显减轻，恢复也更快。新生儿期使用吗啡对成年期的吗啡镇痛效果没有显著影响。有趣的是，未接受吗啡治疗的新生儿期受伤动物，在无外周炎症的情况下，吗啡剂量 - 反应曲线出现明显右移。综上所述，这些结果表明，预防性使用吗啡能显著减轻新生儿期炎症损伤对行为的长期影响。
Despite mounting evidence on the importance of pain management in preterm infants, clinical use of analgesics in this population is limited. Our previous studies have shown that neonatal inflammation results in long-term alterations in adult somatosensory thresholds, characterized by decreased baseline nociceptive sensitivity, and enhanced hyperalgesia following a subsequent inflammatory insult. The present studies were conducted to determine if pre-emptive morphine attenuates these negative consequences. At P0, pups received an injection of morphine sulfate (MS) before an intraplantar injection of 1% carrageenan (CGN). Control pups received either saline (SAL) followed by intraplantar CGN, MS followed by intraplantar SAL, or SAL followed by intraplantar SAL. Pre-emptive morphine significantly attenuated neonatal injury-induced hypoalgesia in adolescence and adulthood. Similarly, morphine pre-treated animals displayed significantly less hyperalgesia and recovered faster from a subsequent inflammatory insult compared to controls. Neonatal morphine had no significant effect on morphine analgesia in adulthood. Interestingly, neonatally injured animals that did not receive morphine displayed a significant rightward shift in the morphine dose response curve in the absence of peripheral inflammation. Together, these results demonstrate that pre-emptive morphine significantly attenuates the long-term behavioral impact of neonatal inflammatory injury.