Wang J Y, Zhao M, Yuan Y K, Fan G X, Jia H, Tang J-S
Department of Immunology and Pathogenic Biology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, PR China.
Neuroscience. 2006;138(4):1319-27. doi: 10.1016/j.neuroscience.2005.11.071. Epub 2006 Feb 10.
Previous studies have indicated that thalamic nucleus submedius is involved in opioid-mediated antinociception in tail flick test and formalin test. The current study examined the effects of opioids microinjected into the thalamic nucleus submedius on the allodynia developed in neuropathic pain model rats, and determined the roles of different subtypes of opioid receptors in the thalamic nucleus submedius opioid-evoked antiallodynia. The allodynic behaviors induced by L5/L6 spinal nerve ligation were assessed by mechanical (von Frey filaments) and cold (4 degrees C plate) stimuli. Morphine (1.0, 2.5, and 5.0 microg) microinjected into the thalamic nucleus submedius contralateral to the nerve injury paw produced a dose-dependent inhibition of the mechanical and cold allodynia, and these effects were reversed by microinjection of the non-selective opioid receptor antagonist naloxone (1.0 microg) into the same site. Microinjection of endomorphin-1 (5.0 microg), a highly selective mu-opioid receptor agonist, and [D-Ala2, D-Leu5]-enkephalin (10 microg), a delta-/mu-opioid receptor agonist, also inhibited the allodynic behaviors, and these effects were blocked by selective mu-opioid receptor antagonist beta-funaltrexamine hydrochloride (3.75 microg). However, the [D-Ala2, D-Leu5]-enkephalin-evoked antiallodynic effects were not influenced by the selective delta-opioid receptor antagonist naltrindole (5.0 microg). Microinjection of the selective kappa-receptor agonist spiradoline mesylate salt (100 microg) into the thalamic nucleus submedius failed to alter the allodynia induced by spinal nerve ligation. These results suggest that the thalamic nucleus submedius is involved in opioid-evoked antiallodynia which is mediated by mu- but not delta- and kappa-opioid receptor in the neuropathic pain model rats.
以往研究表明，丘脑正中核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。本研究检测了向丘脑正中核微量注射阿片类药物对神经病理性疼痛模型大鼠所产生的痛觉过敏的影响，并确定了不同亚型阿片受体在丘脑正中核阿片类药物诱发的抗痛觉过敏中的作用。通过机械性（von Frey细丝）和冷（4℃平板）刺激评估L5/L6脊神经结扎诱导的痛觉过敏行为。向与神经损伤爪对侧的丘脑正中核微量注射吗啡（1.0、2.5和5.0微克）可产生剂量依赖性的对机械性和冷痛觉过敏的抑制作用，且这些作用可被向同一部位微量注射非选择性阿片受体拮抗剂纳洛酮（1.0微克）所逆转。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（10微克）也可抑制痛觉过敏行为，且这些作用可被选择性μ-阿片受体拮抗剂盐酸β-芬太尼（3.75微克）所阻断。然而，[D-Ala2，D-Leu5]-脑啡肽诱发的抗痛觉过敏作用不受选择性δ-阿片受体拮抗剂纳曲吲哚（5.0微克）的影响。向丘脑正中核微量注射选择性κ-受体激动剂甲磺酸螺哌多林（100微克）未能改变脊神经结扎诱导的痛觉过敏。这些结果表明，在神经病理性疼痛模型大鼠中，丘脑正中核参与了由μ-阿片受体而非δ-和κ-阿片受体介导的阿片类药物诱发的抗痛觉过敏。
