Zhao Mei, Wang Jun-Yang, Jia Hong, Tang Jing-Shi
Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, People's Republic of China.
Brain Res. 2006 Mar 3;1076(1):68-77. doi: 10.1016/j.brainres.2006.01.018. Epub 2006 Feb 13.
Previous studies have indicated that the ventrolateral orbital cortex (VLO) is involved in opioid-mediated antinociception in the tail flick test and formalin test. The aim of the current study was to examine the effect of opioids microinjected into the VLO on allodynia in the rat L5/L6 spinal nerve ligation (SNL) model of neuropathic pain and determine the roles of different subtypes of opioid receptors in this effect. The allodynia was assessed by both mechanical (von Frey filaments) and cold plate (4 degrees C) stimuli. Morphine (1.0, 2.5, and 5.0 microg) microinjected into the VLO contralateral to the nerve ligation dose-dependently depressed the mechanical and cold allodynia and these effects were reversed by nonselective opioid receptor antagonist naloxone (1.0 microg) administrated into the same site. Microinjection of endomorphin-1 (5.0 microg), a highly selective mu-opioid receptor agonist, and [D-Ala2, D-Leu5]-enkephalin (DADLE, 10 microg), a delta-/mu-opioid receptor agonist, also depressed the allodynia, and the effects of both drugs were blocked by selective mu-receptor antagonist beta-funaltrexamine (beta-FNA, 3.75 microg), but the effects of DADLE were not influenced by the selective delta-receptor antagonist naltrindole (5.0 microg). Microinjection of U-62066 (100 microg), a kappa-opioid receptor agonist, into the VLO had no effect on the allodynia. These results suggest that the VLO is involved in opioid-induced antiallodynia and mu- but not delta- and kappa-opioid receptor mediates these effects in the rat with neuropathic pain.
先前的研究表明,腹外侧眶皮质(VLO)参与了甩尾试验和福尔马林试验中阿片类药物介导的抗伤害感受。本研究的目的是检测向VLO微量注射阿片类药物对大鼠L5/L6脊髓神经结扎(SNL)神经性疼痛模型中异常性疼痛的影响,并确定不同亚型阿片受体在该效应中的作用。通过机械刺激(von Frey细丝)和冷板刺激(4℃)评估异常性疼痛。向神经结扎对侧的VLO微量注射吗啡(1.0、2.5和5.0微克)可剂量依赖性地减轻机械性和冷刺激诱发的异常性疼痛,且这些效应可被注射到同一部位的非选择性阿片受体拮抗剂纳洛酮(1.0微克)逆转。微量注射高选择性μ阿片受体激动剂内吗啡肽-1(5.0微克)和δ/μ阿片受体激动剂[D-Ala2,D-Leu5]-脑啡肽(DADLE,10微克)也可减轻异常性疼痛,两种药物的效应均被选择性μ受体拮抗剂β-芬太尼丁(β-FNA,3.75微克)阻断,但DADLE的效应不受选择性δ受体拮抗剂纳曲吲哚(5.0微克)的影响。向VLO微量注射κ阿片受体激动剂U-62066(100微克)对异常性疼痛无影响。这些结果表明,VLO参与了阿片类药物诱导的抗异常性疼痛,且μ阿片受体而非δ和κ阿片受体介导了这些效应,在患有神经性疼痛的大鼠中。