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首页> 外文期刊>The journal of pain: official journal of the American Pain Society >Differential development of antinociceptive tolerance to morphine and fentanyl is not linked to efficacy in the ventrolateral periaqueductal gray of the rat
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Differential development of antinociceptive tolerance to morphine and fentanyl is not linked to efficacy in the ventrolateral periaqueductal gray of the rat

机译：吗啡和芬太尼抗伤害感受耐受的差异发展与大鼠腹外侧导水管周围灰质的功效没有关系

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摘要

Systemic administration of morphine typically produces greater tolerance than higher efficacy mu-opioid receptor (MOPr) agonists such as fentanyl. The objective of the present study was to test this relationship by measuring antinociceptive efficacy and tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray (vlPAG). MOPr agonist efficacy was evaluated by microinjecting the irreversible opioid receptor antagonist β-funaltrexamine hydrochloride (β-FNA) into the vlPAG prior to a dose-response analysis of morphine and fentanyl antinociception. In contrast to systemic administration of morphine and fentanyl, microinjection of these drugs into the vlPAG had similar efficacy as measured by similar reductions in maximal antinociception following β-FNA administration. Analysis of tolerance revealed a rightward shift in the dose-response curve to a single pretreatment with morphine, but not fentanyl. The magnitude of tolerance to morphine was comparable following 1, 4, or 8 pretreatments. Tolerance to fentanyl also was evident following 4 or 8 microinjections. These data are surprising in that antinociceptive efficacy appears to vary depending on the site of administration. Moreover, the similar efficacy following microinjection of morphine and fentanyl into the vlPAG was associated with comparable tolerance, with the 1 exception of no tolerance to acute administration of fentanyl. Perspective: These data reveal that antinociceptive tolerance following vlPAG administration of opioids develops rapidly and is evident with both morphine and fentanyl, and the magnitude is relatively consistent regardless of the number of pretreatments.
机译：与更高功效的μ阿片受体（MOPr）激动剂（如芬太尼）相比，吗啡的全身给药通常产生更大的耐受性。本研究的目的是通过测量对腹侧导水管周围灰质（vlPAG）微注射的吗啡和芬太尼的镇痛效果和耐受性来测试这种关系。在对吗啡和芬太尼抗伤害感受的剂量反应分析之前，通过将不可逆的阿片受体拮抗剂β-氟苯氨胺盐酸盐（β-FNA）微量注射到vlPAG中来评估MOPr激动剂的疗效。与吗啡和芬太尼的全身性给药相反，将这些药物显微注射到vlPAG中具有相似的功效，如通过β-FNA给药后最大抗伤害感受力的相似降低所测。耐受性分析显示，剂量反应曲线向右移动至使用吗啡而非芬太尼进行单次预处理。经过1、4或8次预处理后，对吗啡的耐受程度可比。注射4或8次后，芬太尼的耐受性也很明显。这些数据令人惊讶，因为抗伤害感受的功效似乎根据给药部位而变化。此外，将吗啡和芬太尼微注射到vlPAG中后的相似功效与相当的耐受性相关，其中1个例外是对芬太尼的急性给药没有耐受性。观点：这些数据表明，vlPAG给予阿片类药物后，抗伤害感受的耐受性迅速发展，并且在吗啡和芬太尼中均很明显，并且无论进行何种预处理，其幅度都相对一致。

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