Paradoxical hyperalgesia induced by mu-opioid receptor agonist endomorphin-2, but not endomorphin-1, microinjected into the centromedial amygdala of the rat.
Paradoxical hyperalgesia induced by mu-opioid receptor agonist endomorphin-2, but not endomorphin-1, microinjected into the centromedial amygdala of the rat.
复制标题
将 mu-阿片受体激动剂内吗啡肽 2（而非内吗啡肽 1）显微注射到大鼠杏仁核中心内侧诱导的反常痛觉过敏。
DOI：
10.1016/j.ejphar.2006.10.014
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发表时间：
2007
影响因子：
5
通讯作者：
Tseng,LeonF
中科院分区：
文献类型：
--
作者：
Terashvili,Maia;Wu,Hsiang-En;Schwasinger,Emma;Tseng,LeonF
在雄性 CD 大鼠中研究了内吗啡肽 2 或内吗啡肽 1 显微注射到中央杏仁核对热诱导的甩尾反应的影响。将内啡肽-2（8.7–35.0 nmol）显微注射到杏仁核中心内侧，时间和剂量依赖性地降低了甩尾潜伏期。另一方面，将内啡肽-1 (8–32.6 nmol) 注入同一位点不会引起甩尾潜伏期的任何变化。然而，给予杏仁核基底外侧部位的内吗啡肽 1 (32.6 nmol) 或内吗啡肽 2 (35.0 nmol) 并不影响甩尾潜伏期。用强啡肽 A(1–17) 抗血清（200 μg）进行预处理可显着逆转内吗啡肽-2 引起的甩尾潜伏期的减少。内吗啡肽 2 诱导的甩尾潜伏期的减少也被内吗啡肽 2 选择性 μ-阿片受体拮抗剂 3-甲氧基纳曲酮 (6.4 pmol) 和 N-甲基-d-天冬氨酸 (NMDA) 受体拮抗剂 MK-801 (30 nmol) 阻断，但不能被 κ-阿片受体拮抗剂去甲二托菲明 (nor-binaltorphimine) (6.6 nmol) 阻断。结论是，内吗啡肽 2（而非内吗啡肽 1）注入中央杏仁核会刺激 3-甲氧基纳曲酮敏感的 μ-阿片受体亚型，诱导强啡肽 A(1-17) 的释放，然后作用于 NMDA 受体，但不作用于 κ-阿片受体，产生痛觉过敏。这一结论得到了其他研究结果的进一步支持，即给予中央杏仁核的强啡肽 A(1–17) (2.3 nmol) 也导致甩尾潜伏期的缩短，这种现象同样被 NMDA 受体拮抗剂 MK-801 (30 nmol) 所阻断，但 κ-阿片受体拮抗剂去甲二醛托菲明 (nor-binaltorphimine) (6.6 nmol) 则不能阻断这一现象。
The effects of endomorphin-2 or endomorphin-1 microinjected into the centromedial amygdala on the thermally-induced tail-flick response were studied in male CD rats. Microinjection of endomorphin-2 (8.7–35.0 nmol) given into the centromedial amygdala time- and dose-dependently decreased the tail-flick latencies. On the other hand, endomorphin-1 (8–32.6 nmol) given into the same site did not cause any change of the tail-flick latency. However, endomorphin-1 (32.6 nmol) or endomorphin-2 (35.0 nmol) given into the basolateral site of amygdala did not affect the tail-flick latency. Pretreatment with the antiserum against dynorphin A(1–17) (200 μg) significantly reversed the decrease of the tail-flick latency induced by endomorphin-2. The decrease of the tail-flick latency induced by endomorphin-2 was also blocked by the endomorphin-2 selective μ-opioid receptor antagonist 3-methoxynaltrexone (6.4 pmol) and by the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 (30 nmol), but not by the κ-opioid receptor antagonist nor-binaltorphimine (6.6 nmol). It is concluded that endomorphin-2, but not endomorphin-1, given into the centromedial amygdala stimulates a 3-methoxynaltrexone-sensitive μ-opioid receptor subtype to induce the release of dynorphin A(1–17), which then acts on the NMDA receptor, but not κ-opioid receptor for producing hyperalgesia. This conclusion is further supported by the additional findings that dynorphin A(1–17) (2.3 nmol) given into the centromedial amygdala also caused the decrease of the tail-flick latency, which was similarly blocked by the NMDA receptor antagonist MK-801 (30 nmol), but not κ-opioid receptor antagonist nor-binaltorphimine (6.6 nmol).