de Araujo Lucas G, Alster P, Brodin E, Wiesenfeld-Hallin Z
Karolinska Institute, Department of Medical Laboratory Sciences and Technology, Huddinge University Hospital, Sweden.
Neurosci Lett. 1998 Mar 27;245(1):13-6. doi: 10.1016/s0304-3940(98)00163-3.
The analgesic efficacy of opioids is reduced in neuropathic pain states and increased in inflammation. Since the neuropeptide cholecystokinin (CCK) plays a role in the modulation of opiate-induced analgesia, the morphine-mediated release of CCK in the spinal cord of rats was compared with in vivo microdialysis in normals and different pain models. The effect of systemic and intrathecal (i.t.) morphine on the extracellular level of CCK was analyzed in the spinal cord dorsal horn of halothane-anaesthetized normal rats as well as during peripheral neuropathy and inflammation. No difference was found in basal CCK level among groups. However, morphine significantly increased extracellular CCK concentration after both systemic and spinal application in intact as well as axotomized rats and this effect was naloxone-reversible in non-lesioned animals. Similar results were seen in axotomized rats. In contrast, morphine did not induce CCK release during carrageenan-induced inflammation. These data provide evidence that the ability of opiates to release CCK under different pain states may play a key role in their analgesic efficacy.
阿片类药物在神经性疼痛状态下的镇痛效果会降低，而在炎症状态下会增强。由于神经肽胆囊收缩素（CCK）在阿片类药物诱导的镇痛调节中发挥作用，因此将大鼠脊髓中吗啡介导的CCK释放与正常和不同疼痛模型中的体内微透析进行了比较。在氟烷麻醉的正常大鼠以及周围神经病变和炎症期间，分析了全身和鞘内注射吗啡对脊髓背角CCK细胞外水平的影响。各组之间的基础CCK水平未发现差异。然而，在完整大鼠和轴突切断大鼠中，全身和脊髓应用吗啡后均显著增加了细胞外CCK浓度，且在未损伤动物中这种作用可被纳洛酮逆转。在轴突切断大鼠中也观察到了类似结果。相比之下，在角叉菜胶诱导的炎症期间，吗啡并未诱导CCK释放。这些数据表明，阿片类药物在不同疼痛状态下释放CCK的能力可能在其镇痛效果中起关键作用。
