Micro-opioid receptor agonist injections into the presumed pre-Botzinger complex and the surrounding region of awake goats do not alter eupneic breathing.
Micro-opioid receptor agonist injections into the presumed pre-Botzinger complex and the surrounding region of awake goats do not alter eupneic breathing.
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将微阿片受体激动剂注射到假定的前博辛格复合体和清醒山羊的周围区域不会改变平静呼吸。
DOI：
10.1152/japplphysiol.90548.2008
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Forster,HV
中科院分区：
文献类型：
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作者：
Krause,KL;Neumueller,SE;Marshall,BD;Kiner,T;Bonis,JM;Pan,LG;Qian,B;Forster,HV
阿片类药物在缓解疼痛方面具有重要的临床意义。阿片类药物的不良副作用是呼吸抑制。来自分离制剂的数据表明，这种效应是由于前Bötzinger复合体(PreböTzc)中神经元的放电活动减弱所致，PreböTzC是一个具有呼吸节律特性的髓质区。本研究的目的是观察μ阿片受体激动剂[d-丙氨酸(2)，N-Me-苯丙氨酸(4)，甘氨酸(5)-醇]-脑啡肽(DAMGO)对成年清醒山羊的呼吸的影响。我们假设，当DAMGO注射到假定的PreböTzC和清醒动物的周围区域时，会导致呼吸减少和变得不规律。我们进一步假设，注射DAMGO后，对二氧化碳和缺氧的通气性敏感性将被钝化。将微管植入10只成年雌性山羊的双侧PreböTzC内。术后恢复后，在清醒状态下向假定的PrebötzC内注射达美尔(0.5-10μL，1 NM-10μM)。DAMGO对肺通气量[吸气分钟通气量(V̇I)]、呼吸节律和模式、吸气肌和呼气肌的激活模式以及正常呼吸状态下的动脉血气均无影响(P&gT；0.10)。然而，DAMGO可减弱吸入CO2时引起的呼吸频率增加(P<；0.05)，并可使吸入O2减少时的V-̇反应减弱至10.8%(P<；0.05)。我们的结论是，我们的数据不支持这样的概念，即在清醒的哺乳动物中，阿片类药物对呼吸的抑制是由于阿片类药物对PreböTzC神经元的直接作用。
Opioids are clinically important in the alleviation of pain. An undesirable side effect of opioids is depression of breathing. Data from isolated preparations suggest this effect is due to attenuation of discharge activity of neurons in the pre-Bötzinger complex (preBötzC), a medullary area with respiratory rhythmogenic properties. The purpose of this study was to examine how [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO), a μ-opioid receptor agonist, affected breathing after injection into the presumed preBötzC of the adult awake goat. We hypothesized that DAMGO would cause breathing to decrease and become irregular when injected into the presumed preBötzC and the surrounding region of the conscious animal. We further hypothesized that ventilatory sensitivity to CO2and hypoxia would be blunted after the injection of DAMGO. Microtubules were bilaterally implanted into the presumed preBötzC of 10 adult female goats. After recovery from the surgery, DAMGO (0.5–10 μl, 1 nM–10 μM) was injected into the presumed preBötzC during the awake state. DAMGO had no effect on pulmonary ventilation [inspiratory minute ventilation (V̇i)], respiratory rhythm and pattern, the activation pattern of inspiratory and expiratory muscles, or arterial blood gases during eupneic breathing conditions (P> 0.10). However, DAMGO attenuated (P< 0.05) the evoked increase in breathing frequency when inspired CO2was increased, and DAMGO attenuated the V̇iresponse to reduction of inspired O2to 10.8% (P< 0.05). We conclude that our data do not provide support for the concept that in awake mammals opioid depression of breathing is due to a directed action of opioids on preBötzC neurons.