Pathophysiology Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive, SE, Albuquerque, NM 87108, United States.
Brain Res. 2012 Aug 21;1469:73-81. doi: 10.1016/j.brainres.2012.06.028. Epub 2012 Jun 30.
Our previous study has shown that activating peripheral μ-receptors is necessary for switching the bronchopulmonary C-fibers (PCFs)-mediated rapid shallow breathing (RSB) into an apnea by systemic administration of fentanyl. The brainstem nuclei, such as the medial nucleus tractus solitarius (mNTS) and the pre-Botzinger complex (PBC), are required for completing the PCF-mediated respiratory reflexes. Moreover, these areas contain abundant μ-receptors and their activation prolongs expiratory duration (T(E)). Thus, we asked if central μ-receptors, especially those in the mNTS and PBC, are involved in fully expressing this RSB-apnea switch by fentanyl. In anesthetized rats, the cardiorespiratory responses to right atrial injection of phenylbiguanide (PBG, 3-6μg/kg) were repeated after: (1) fentanyl (iv), a μ-receptor agonist, alone (8μg/kg, iv); (2) fentanyl following microinjection of naloxone methiodide (NXM, an opioid receptor antagonist) into the cisterna magna (10μg/4μl); (3) the bilateral mNTS (10mM, 20nl); or (4) PBC (10mM, 20nl). Our results showed that PBG shortened T(E) by 37±6% (RSB, from 0.41±0.05 to 0.26±0.03s, P<0.01), but it markedly prolonged T(E) by 5.8-fold (an apnea, from 0.50±0.04s to 2.9±0.57s, P<0.01) after fentanyl (iv). Pretreatment with NXM injected into the cisterna magna or the PBC, but not the mNTS, prevented the fentanyl-induced switch. This study, along with our previous results mentioned above, suggests that although peripheral μ-receptors are essential for triggering the fentanyl-induced switch, central μ-receptors, especially those in the PBC, are required to fully exhibit such switch.
Our results suggest that the activation of central μ-receptors, especially those in the pre-Botzinger complex, is required for switching the pulmonary C-fiber-mediated rapid shallow breathing into an apnea by systemic administration of fentanyl.
我们之前的研究表明，通过全身给予芬太尼，激活外周 μ 受体对于将肺 C 纤维（PCF）介导的快速浅呼吸切换为呼吸暂停是必要的。脑干核，如孤束核（mNTS）和 Pre-Botzinger 复合体（PBC），对于完成 PCF 介导的呼吸反射是必需的。此外，这些区域含有丰富的 μ 受体，其激活可延长呼气时间（T(E)）。因此，我们想知道中央 μ 受体，特别是 mNTS 和 PBC 中的 μ 受体，是否参与了芬太尼完全表达这种快速浅呼吸-呼吸暂停转换。在麻醉大鼠中，重复右心房注射苯并胍（PBG，3-6μg/kg）后的心肺反应：（1）芬太尼（iv），μ 受体激动剂，单独（8μg/kg，iv）；（2）芬太尼后鞘内注射纳洛酮甲碘化物（NXM，阿片受体拮抗剂）（10μg/4μl）；（3）双侧孤束核（10mM，20nl）；或（4）PBC（10mM，20nl）。我们的结果表明，PBG 将 T(E)缩短了 37±6%（RSB，从 0.41±0.05 到 0.26±0.03s，P<0.01），但芬太尼（iv）后，T(E)显著延长了 5.8 倍（呼吸暂停，从 0.50±0.04 到 2.9±0.57s，P<0.01）。鞘内注射 NXM 或 PBC，但不是孤束核，预处理可防止芬太尼引起的转换。这项研究，以及我们之前提到的结果，表明尽管外周 μ 受体对于触发芬太尼诱导的转换是必需的，但中枢 μ 受体，特别是 PBC 中的 μ 受体，对于完全表现出这种转换是必需的。
我们的结果表明，激活中枢 μ 受体，特别是 Pre-Botzinger 复合体中的 μ 受体，对于通过全身给予芬太尼将肺 C 纤维介导的快速浅呼吸切换为呼吸暂停是必要的。
