口服吗啡通过使用阿片类受体独立的机制诱导脊柱5-二三胺 (5-HT) 释放
Shingo Nakamura1, Shuji Komatsu1, Toshihiko Yamada1
1Department of Anesthesiology, Kumamoto University Hospital, Kumamoto, Japan.
Pharmacology research & perspectives
|July 24, 2023
概括
口服吗啡显著增加了大鼠的脊髓5-二三胺 (5-HT) 释放,独立于阿片类受体. 持续的疼痛增强了这种吗啡诱导的5-HT释放,尽管它不会显著影响吗啡的止痛作用.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 疼痛研究 疼痛研究
背景情况:
- 众所周知,吗啡会触发脊髓中的5-基三胺 (5-HT) 释放.
- 吗啡诱导的脊柱5-HT释放的确切机制和功能意义尚不清楚.
- 持续疼痛对这个过程的影响还不太清楚.
研究的目的:
- 阐明由口服吗啡诱导的脊柱5-HT释放的作用和机制.
- 为了研究持续的疼痛是否调节由口服吗啡引起的脊柱5-HT释放.
主要方法:
- 在清醒的老鼠中,使用腰椎大脑脊髓液 (CSF) 的微透析量化脊椎5-HT释放.
- 进行了吗啡和 oxycodone 的口服,并测量了 5-HT 释放.
- 使用纳洛和β-funaltrexamine (β-FNA) 评估了阿片类受体的参与.
- 通过甲胺测试诱导持续性疼痛,以检查其对吗啡诱导的5-HT释放的影响.
主要成果:
- 口服吗啡,与氧化不同,脊柱5-HT水平增加了大约4000%的基线.
- 这种吗啡诱导的5-HT释放并未被纳洛或β-FNA阻断,即使在剂量有效地对抗吗啡的抗受体作用.
- 持续的疼痛没有改变基底脊柱的5-HT释放,但显著放大了口服吗啡诱导的5-HT释放.
- 口服吗啡引发的脊柱5-HT释放并没有通过阿片类受体激活来调节.
- 在热板测试中,脊柱5-HT似乎不是吗啡抗受体作用的主要调解者.
结论:
- 口服吗啡通过非阿片类受体介导的途径诱导显著的脊柱5-HT释放.
- 持续的疼痛增强了口服吗啡诱导的脊柱5-HT释放.
- 口服吗啡释放的脊柱5-HT可能不会在它的止痛作用中发挥关键作用,这表明了其他机制.
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