Fentanyl effects on respiratory neuron activity in the dorsolateral pons.
Fentanyl effects on respiratory neuron activity in the dorsolateral pons.
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DOI：
10.1152/jn.00113.2022
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发表时间：
2022-11-01
影响因子：
2.5
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中科院分区：
文献类型：
--
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阿片类药物通过脑干中的作用抑制呼吸，包括背外侧脑桥的与呼吸相关的区域，该区域包含多种呼吸模式神经元的表型。受阿片类药物影响的背外侧脑桥神经元的放电特性尚不清楚。为了解决这一问题，记录单个神经元单位的背外侧脑桥动脉灌注原位大鼠制剂，灌注与阿片类药物激动剂芬太尼的窒息浓度，其次是阿片类药物拮抗剂纳洛酮（NLX）。背外侧脑桥神经元进行分类的基础上，麻醉相关的放电模式，这是不同的影响芬太尼。在芬太尼诱导的呼吸暂停过程中，吸气神经元和吸气/呼气跨相神经元的子集被沉默或放电频率降低，这在纳洛酮给药后被逆转。相比之下，大多数呼气神经元继续发射紧张性在芬太尼诱导的呼吸暂停，虽然与减少发射频率。此外，在芬太尼诱导的呼吸暂停和纳洛酮介导的恢复过渡期间，脑桥吸气后期和吸气后神经元活动不存在于呼吸暂停样呼吸中。因此，阿片类药物诱导的呼吸模式缺陷可能是由于脑桥吸气神经元的活动减少而发生的，而呼吸暂停则是由于所有阶段性脑桥活动和持续的紧张性呼气神经元活动的丧失而发生的。新&值得注意的阿片类药物可以抑制呼吸通过整个脑干的行动，包括背外侧脑桥。阿片类药物抑制脑桥背外侧神经元的呼吸表型尚不清楚。在这里，我们描述了高效阿片类芬太尼对这些背外侧脑桥神经元放电活动的影响。吸入神经元在很大程度上沉默芬太尼，而呼气神经元没有。我们提供了一个框架，这种差异敏感性芬太尼可以有助于呼吸模式的缺陷和呼吸暂停。
Opioids suppress breathing through actions in the brainstem, including respiratory-related areas of the dorsolateral pons, which contain multiple phenotypes of respiratory patterned neurons. The discharge identity of dorsolateral pontine neurons that are impacted by opioids is unknown. To address this, single neuronal units were recorded in the dorsolateral pons of arterially perfused in situ rat preparations that were perfused with an apneic concentration of the opioid agonist fentanyl, followed by the opioid antagonist naloxone (NLX). Dorsolateral pontine neurons were categorized based on respiratory-associated discharge patterns, which were differentially affected by fentanyl. Inspiratory neurons and a subset of inspiratory/expiratory phase-spanning neurons were either silenced or had reduced firing frequency during fentanyl-induced apnea, which was reversed upon administration of naloxone. In contrast, the majority of expiratory neurons continued to fire tonically during fentanyl-induced apnea, albeit with reduced firing frequency. In addition, pontine late-inspiratory and postinspiratory neuronal activity were absent from apneustic-like breaths during the transition to fentanyl-induced apnea and the naloxone-mediated transition to recovery. Thus, opioid-induced deficits in respiratory patterning may occur due to reduced activity of pontine inspiratory neurons, whereas apnea occurs with loss of all phasic pontine activity and sustained tonic expiratory neuron activity. NEW & NOTEWORTHY Opioids can suppress breathing via actions throughout the brainstem, including the dorsolateral pons. The respiratory phenotype of dorsolateral pontine neurons inhibited by opioids is unknown. Here, we describe the effect of the highly potent opioid fentanyl on the firing activity of these dorsolateral pontine neurons. Inspiratory neurons were largely silenced by fentanyl, whereas expiratory neurons were not. We provide a framework whereby this differential sensitivity to fentanyl can contribute to respiratory pattern deficits and apnea.
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影响因子：
2.3
作者：
Bonis, J. M.;Neumueller, S. E.;Krause, K. L.;Pan, L. G.;Hodges, M. R.;Forster, H. V.
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Forster, H. V.
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