Bingham S, Davey P T, Babbs A J, Irving E A, Sammons M J, Wyles M, Jeffrey P, Cutler L, Riba I, Johns A, Porter R A, Upton N, Hunter A J, Parsons A A
Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park North, 3rd Avenue, Essex CM19 5AW, Harlow, UK.
Pain. 2001 May;92(1-2):81-90. doi: 10.1016/s0304-3959(00)00470-x.
The hypothalamic peptide orexin-A and the orexin-1 receptor are localized in areas of the brain and spinal cord associated with nociceptive processing. In the present study, localization was confirmed in the spinal cord and demonstrated in the dorsal root ganglion for both orexin-A and the orexin-1 receptor. The link with nociception was extended when orexin-A was shown to be analgesic when given i.v. but not s.c. in mouse and rat models of nociception and hyperalgesia. The efficacy of orexin-A was similar to that of morphine in the 50 degrees C hotplate test and the carrageenan-induced thermal hyperalgesia test. However, involvement of the opiate system in these effects was ruled out as they were blocked by the orexin-1 receptor antagonist SB-334867 but not naloxone. Orexin-1 receptor antagonists had no effect in acute nociceptive tests but under particular inflammatory conditions were pro-hyperalgesic, suggesting a tonic inhibitory orexin drive in these circumstances. These data demonstrate that the orexinergic system has a potential role in the modulation of nociceptive transmission.
下丘脑肽食欲素A和食欲素-1受体定位于大脑和脊髓中与伤害性刺激处理相关的区域。在本研究中，食欲素A和食欲素-1受体在脊髓中的定位得到了证实，并在背根神经节中得到了显示。当在小鼠和大鼠的伤害性感受和痛觉过敏模型中静脉注射而非皮下注射食欲素A显示出镇痛作用时，其与伤害性感受的联系得到了扩展。在50摄氏度热板试验和角叉菜胶诱导的热痛觉过敏试验中，食欲素A的效果与吗啡相似。然而，阿片系统参与这些效应被排除，因为它们被食欲素-1受体拮抗剂SB-334867阻断，而不是被纳洛酮阻断。食欲素-1受体拮抗剂在急性伤害性感受试验中没有作用，但在特定的炎症条件下会促进痛觉过敏，表明在这些情况下存在一种紧张性抑制性食欲素驱动。这些数据表明，食欲素能系统在伤害性感受传递的调节中具有潜在作用。
