Terashvili Maia, Wu Hsiang-En, Schwasinger Emma, Tseng Leon F
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Eur J Pharmacol. 2007 Jan 12;554(2-3):137-44. doi: 10.1016/j.ejphar.2006.10.014. Epub 2006 Oct 17.
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 microg) 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 micro-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 kappa-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 mu-opioid receptor subtype to induce the release of dynorphin A(1-17), which then acts on the NMDA receptor, but not kappa-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 kappa-opioid receptor antagonist nor-binaltorphimine (6.6 nmol).
在雄性CD大鼠中，研究了向中央杏仁核微量注射内吗啡肽-2或内吗啡肽-1对热诱导甩尾反应的影响。向中央杏仁核微量注射内吗啡肽-2（8.7 - 35.0纳摩尔）可使甩尾潜伏期呈时间和剂量依赖性缩短。另一方面，向同一部位注射内吗啡肽-1（8 - 32.6纳摩尔）并未引起甩尾潜伏期的任何变化。然而，向杏仁核基底外侧部位注射内吗啡肽-1（32.6纳摩尔）或内吗啡肽-2（35.0纳摩尔）并不影响甩尾潜伏期。用抗强啡肽A(1 - 17)抗血清（200微克）预处理可显著逆转内吗啡肽-2诱导的甩尾潜伏期缩短。内吗啡肽-2选择性微阿片受体拮抗剂3 - 甲氧基纳曲酮（6.4皮摩尔）和N - 甲基 - D - 天冬氨酸（NMDA）受体拮抗剂MK - 801（30纳摩尔）也可阻断内吗啡肽-2诱导的甩尾潜伏期缩短，但κ阿片受体拮抗剂去甲二氢吗啡酮（6.6纳摩尔）则不能。得出的结论是，向中央杏仁核注射内吗啡肽-2而非内吗啡肽-1可刺激一种对3 - 甲氧基纳曲酮敏感的μ阿片受体亚型，从而诱导强啡肽A(1 - 17)释放，然后强啡肽A(1 - 17)作用于NMDA受体而非κ阿片受体以产生痛觉过敏。向中央杏仁核注射强啡肽A(1 - 17)（2.3纳摩尔）也会导致甩尾潜伏期缩短，且同样被NMDA受体拮抗剂MK - 801（30纳摩尔）阻断但不被κ阿片受体拮抗剂去甲二氢吗啡酮（6.6纳摩尔）阻断，这一额外发现进一步支持了该结论。
