Antinociceptive tolerance to NSAIDs microinjected into dorsal hippocampus.

Antinociceptive tolerance to NSAIDs microinjected into dorsal hippocampus.
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DOI:
10.1186/2050-6511-15-10
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发表时间:
2014-02-28
影响因子:
2.9
通讯作者:
Tsagareli MG
Tsagareli MG
中科院分区:
医学4区
文献类型:
--
作者:
Gurtskaia G;Tsiklauri N;Nozadze I;Nebieridze M;Tsagareli MG

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疼痛的特征是一种复杂的体验,不仅依赖于伤害性感觉系统的调节,而且依赖于控制边缘脑区域(如杏仁核和海马体)中情绪过程的机制的激活。一些研究表明,在某些脑区,特别是中脑导水管周围灰质,延髓头端腹内侧,杏仁核中央核和中缝大核,非甾体抗炎药(NSAID)的微量注射诱导抗伤害性感受与耐受性的明显发展。本研究旨在探讨是否NSAIDs,氯地芬,酮咯酸和xefocam微量注射到背海马(DH)导致的抗伤害耐受性的发展在雄性大鼠。实验在实验和对照(盐水)白色雄性大鼠上进行。动物在DH中植入引导套管,并在甩尾(TF)和热板(HP)试验中将NSAID微量注射到DH中后测试抗伤害感受。采用事后Tukey-Kramer多重比较检验的方差分析重复测量进行统计学评价。我们发现,微量注射这些非甾体抗炎药到DH诱导抗伤害性感受所揭示的TF和HP测试的潜伏期增加相比,对照组用盐水到DH。然而,随后在第2天和第3天的试验显示,NSAID的抗伤害作用逐渐降低,表明对NSAID的这种作用产生了耐受性。在两种疼痛模型中,用阿片类拮抗剂纳洛酮治疗前和治疗后均显著降低了NSAID的抗伤害作用。我们的研究结果表明,微量注射非甾体抗炎药到DH诱导的镇痛作用,这是通过阿片系统介导的,并表现出耐受性。
Pain is characterized as a complex experience, dependent not only on the regulation of nociceptive sensory systems, but also on the activation of mechanisms that control emotional processes in limbic brain areas such as the amygdala and the hippocampus. Several lines of investigations have shown that in some brain areas, particularly the midbrain periaqueductal gray matter, rostral ventro-medial medulla, central nucleus of amygdala and nucleus raphe magnus, microinjections of non-steroidal anti-inflammatory drugs (NSAIDs) induce antinociception with distinct development of tolerance. The present study was designed to examine whether microinjection of NSAIDs, clodifen, ketorolac and xefocam into the dorsal hippocampus (DH) leads to the development of antinociceptive tolerance in male rats. The experiments were carried out on experimental and control (with saline) white male rats. Animals were implanted with a guide cannula in the DH and tested for antinociception following microinjection of NSAIDs into the DH in the tail-flick (TF) and hot plate (HP) tests. Repeated measures of analysis of variance with post-hoc Tukey-Kramer multiple comparison tests were used for statistical evaluations. We found that microinjection of these NSAIDs into the DH induces antinociception as revealed by a latency increase in the TF and HP tests compared to controls treated with saline into the DH. Subsequent tests on days 2 and 3, however, showed that the antinociceptive effect of NSAIDs progressively decreased, suggesting tolerance developed to this effect of NSAIDs. Both pretreatment and post-treatment with the opioid antagonist naloxone into the DH significantly reduced the antinociceptive effect of NSAIDs in both pain models. Our results indicate that microinjection of NSAIDs into the DH induces antinociception which is mediated via the opioid system and exhibits tolerance.
周围灰色神经元的围绕灰色神经元在延端腹侧髓质中投射GABA能神经元。
DOI: 10.1016/j.pain.2008.09.009
发表时间: 2008-11-30
期刊: Pain
影响因子: 7.4
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Morgan MM;Whittier KL;Hegarty DM;Aicher SA
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发表时间: 2012-04-25
期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
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DOI: 10.1124/jpet.106.109470
发表时间: 2006-12-01
影响因子: 3.5
作者:
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通讯作者: McCarson, Kenneth E.
DOI: 10.1016/j.ejphar.2006.07.027
发表时间: 2006-09-28
影响因子: 5
作者:
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DOI: 10.1097/00001756-199710200-00035
发表时间: 1997-10-20
期刊: NEUROREPORT
影响因子: 1.7
作者:
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通讯作者: Wessendorf, MW