Chen T, Cai Q, Hong Y
Department of Anatomy and Physiology, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian 350000, People's Republic of China.
Department of Anatomy and Physiology, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian 350000, People's Republic of China.
Neuroscience. 2006 Aug 25;141(2):965-975. doi: 10.1016/j.neuroscience.2006.04.011. Epub 2006 May 18.
The finding that sensory neuron-specific G-protein-coupled receptor mRNA is solely expressed in small primary sensory neurons suggests involvement of the receptor in nociceptive modulation. The present study was designed to assess effects of intrathecal administration of bovine adrenal medulla 8-22 and (Tyr6)-gamma2-MSH-6-12, selective sensory neuron-specific receptor agonists, on nocifensive behaviors and expression of spinal c-Fos-like immunoreactivity evoked by intraplantar injection of 2.5% formalin in rats. The agonists were administered 10 min before (pretreatment) and/or after (post-treatment) injection of formalin. Pretreatment with bovine adrenal medulla 8-22 dose-dependently (3, 10 and 30 nmol) decreased time lifting and licking the paw mainly in the second phase. Intrathecal bovine adrenal medulla 8-22 (30 nmol) remarkably suppressed nocifensive behaviors in the first and second phases and the expression of formalin-evoked c-Fos-like immunoreactivity in laminae I-II and V-VI of the spinal dorsal horn at L4-5. Moreover, naloxone (20 microg, intrathecal) failed to antagonize the inhibitory effects of bovine adrenal medulla 8-22. Post-treatment with bovine adrenal medulla 8-22 also exerted inhibition on the second phase behaviors in a dose-dependent manner with a similar efficacy observed in pretreatment groups. Furthermore, post-treatment with (Tyr6)-gamma2-MSH-6-12 (0.5, 1.5 and 5 nmol) also suppressed formalin-evoked nocifensive behaviors in the second phase and c-Fos-like immunoreactivity in the spinal dorsal horn similar with bovine adrenal medulla 8-22. Our results suggest that sensory neuron-specific receptor may play an important role in modulation of spinal nociceptive transmission. This is the first to demonstrate that activation of sensory neuron-specific receptor produces analgesia in the persistent pain model.
感觉神经元特异性G蛋白偶联受体mRNA仅在小型初级感觉神经元中表达，这一发现提示该受体参与伤害性调制。本研究旨在评估鞘内注射牛肾上腺髓质8 - 22和（酪氨酸6）-γ2 - 促黑素-6 - 12（选择性感觉神经元特异性受体激动剂）对大鼠足底注射2.5%福尔马林诱发的伤害性防御行为及脊髓c - Fos样免疫反应性表达的影响。激动剂在注射福尔马林前10分钟（预处理）和/或后（后处理）给药。牛肾上腺髓质8 - 22预处理呈剂量依赖性（3、10和30 nmol）减少主要在第二阶段抬爪和舔爪的时间。鞘内注射牛肾上腺髓质8 - 22（30 nmol）显著抑制第一和第二阶段的伤害性防御行为以及L4 - 5脊髓背角I - II层和V - VI层福尔马林诱发的c - Fos样免疫反应性表达。此外，鞘内注射纳洛酮（20μg）未能拮抗牛肾上腺髓质8 - 22的抑制作用。牛肾上腺髓质8 - 22后处理也以剂量依赖性方式对第二阶段行为产生抑制作用，并在预处理组中观察到相似的效果。此外，（酪氨酸6）-γ2 - 促黑素-6 - 12（0.5、1.5和5 nmol）后处理也抑制福尔马林诱发的第二阶段伤害性防御行为以及脊髓背角的c - Fos样免疫反应性，与牛肾上腺髓质8 - 22相似。我们的结果提示感觉神经元特异性受体可能在脊髓伤害性信息传递的调制中起重要作用。这是首次证明在持续性疼痛模型中感觉神经元特异性受体的激活产生镇痛作用。
