Graduate Program in Neuroscience and Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota, 55455, USA.
J Neurosci. 2013 Apr 3;33(14):6093-101. doi: 10.1523/JNEUROSCI.0216-13.2013.
Intrathecal application of morphine is among the most powerful methods used to treat severe chronic pain. However, this approach commonly produces itch sufficiently severe that patients are forced to choose between relief of pain or itch. The neuronal populations responsible for processing and transmitting information underlying itch caused by intrathecal application of morphine have not been identified and characterized. We describe two populations of antidromically identified trigeminothalamic tract (VTT) neurons in anesthetized rats that are differentially affected by morphine and explain several aspects of opioid-induced itch and analgesia. We found that intrathecal application of morphine increased ongoing activity of itch-responsive VTT neurons. In addition, intrathecal application of morphine increased responses to pruritogens injected into the skin and greatly heightened responses to innocuous mechanical stimuli. In contrast, the ongoing activity and responses to noxious pinches in nociceptive VTT neurons were frequently inhibited by the same dose of morphine. These results reveal that i.t. application of morphine affects specific subpopulations of VTT neurons in ways that may produce itch, hyperknesis, alloknesis, and analgesia.
鞘内应用吗啡是治疗严重慢性疼痛的最有效方法之一。然而,这种方法通常会引起严重的瘙痒,迫使患者在缓解疼痛或瘙痒之间做出选择。负责处理和传递鞘内应用吗啡引起瘙痒的信息的神经元群体尚未被识别和表征。我们描述了两种在麻醉大鼠中被逆行识别的三叉丘脑束(VTT)神经元群体,它们受到吗啡的不同影响,并解释了阿片类药物引起的瘙痒和镇痛的几个方面。我们发现鞘内应用吗啡增加了瘙痒反应性 VTT 神经元的持续活动。此外,鞘内应用吗啡增加了皮肤内注射致痒剂的反应,并大大增强了对无害机械刺激的反应。相比之下,同一剂量的吗啡经常抑制伤害性 VTT 神经元的持续活动和对有害刺痛的反应。这些结果表明,鞘内应用吗啡以可能引起瘙痒、超敏反应、异感和镇痛的方式影响 VTT 神经元的特定亚群。