Programa de Pós-Graduação em Medicina, Ciências Médicas, Universidade Federal do Rio Grande do Sul, CEP 90035-003, Porto Alegre, Brazil.
Brain Res. 2011 Jan 7;1367:122-9. doi: 10.1016/j.brainres.2010.10.041. Epub 2010 Oct 23.
Considering the importance of a deeper understanding of the effect throughout life of opioid analgesia at birth, our objective was to determine whether morphine administration in early life, once a day for 7 days in 8-day-old rats, alters the nociceptive response over the short (P16), medium (P30), and long term (P60) and to evaluate which system is involved in the altered nociceptive response. The nociceptive responses were assessed by the formalin test, and the behavior analyzed was the total time spent in biting and flicking of the formalin-injected hindpaw, recorded during the first 5 min (phase I) and from 15-30 min (phase II). The morphine group showed no change in nociceptive response at P16, but at P30 and P60, the nociceptive response was increased in phase I, and in both phases, respectively. At P30 and P60, the animals received a non-steroidal anti-inflammatory drug (indomethacin) or NMDA receptor antagonist (ketamine) 30 min before the formalin test. The increase in the nociceptive response was completely reversed by ketamine, and partially by indomethacin. These results indicate that early morphine exposure causes an increase in the nociceptive response in adult life. It is possible that this lower nociception threshold is due to neuroadaptations in nociceptive circuits, such as the glutamatergic system. Thus, this work demonstrates the importance of evaluating clinical consequences related to early opioid administration and suggests a need for a novel design of agents that may counteract opiate-induced neuroplastic changes.
考虑到深入了解出生时阿片类药物镇痛对生命全程的影响的重要性，我们的目的是确定在 8 天大的大鼠中，每天一次连续 7 天给予吗啡是否会改变短期（P16）、中期（P30）和长期（P60）的痛觉反应，并评估哪种系统参与了改变的痛觉反应。通过福尔马林测试评估痛觉反应，分析的行为是在福尔马林注射后后爪的咬噬和弹动的总时间，在第 1 至 5 分钟（第 I 期）和 15-30 分钟（第 II 期）记录。吗啡组在 P16 时痛觉反应没有变化，但在 P30 和 P60 时，第 I 期痛觉反应增加，两个阶段均如此。在 P30 和 P60 时，动物在福尔马林测试前 30 分钟接受非甾体抗炎药（吲哚美辛）或 NMDA 受体拮抗剂（氯胺酮）。氯胺酮完全逆转了痛觉反应的增加，而吲哚美辛部分逆转了痛觉反应的增加。这些结果表明，早期吗啡暴露会导致成年后痛觉反应增加。这种较低的痛觉阈值可能是由于痛觉回路的神经适应，如谷氨酸能系统。因此，这项工作表明了评估与早期阿片类药物给药相关的临床后果的重要性，并表明需要设计新的药物来对抗阿片类药物引起的神经可塑性变化。
