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What is good for the goose is not always good for the gander 对母鹅有好处的并不总是对公鹅有好处
Pub Date : 1999-03-01 DOI: 10.1016/S1082-3174(99)70046-2
William Maixner
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引用次数: 0
Sex differences in opioid analgesia 阿片类镇痛的性别差异
Pub Date : 1999-03-01 DOI: 10.1016/S1082-3174(99)70045-0
Jeffrey S. Mogil , Benjamin Kest
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引用次数: 80
APS Annual Scientific Meeting: Highlights and previews 美国科学学会年度科学会议:重点和展望
Pub Date : 1999-03-01 DOI: 10.1016/S1082-3174(99)70048-6
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引用次数: 0
Opioid tolerance and dependence 阿片类药物耐受性和依赖性
Pub Date : 1999-03-01 DOI: 10.1016/S1082-3174(99)70013-9
Marian E. Fundytus , Terence J. Coderre

Although opioids are the most commonly used analgesics, their therapeutic efficacy is limited by the development of tolerance and dependence with chronic use. Many studies have examined the possible mechanisms underlying the development of opioid tolerance and dependence. Recently, several groups of investigators have focused on excitatory amino acid receptors, specifically N-methyl-D-aspartate (NMDA) receptors, and related intracellular second messenger systems as possible mediators of opioid tolerance and dependence. The hypothesis proposed in this Focus article is an extension of these models of opioid tolerance and dependence, which suggests that metabotropic glutamate receptors (mGluRs) play a key role in the development of opioid tolerance and dependence. We propose that activity at group I mGluRs (and possibly also δ-opioid receptors), which are positively coupled to phosphatidylinositol (PI) hydrolysis, increases during chronic morphine administration. This ultimately leads to increased activation of protein kinase C, with concomitant phosphorylation of μ-opioid receptors (desensitizing them), and the ion channel associated with the NMDA receptor (allowing increased influx of Ca2+). We also suggest that there is a heterologous desensitization of group II and III mGluRs, which are negatively coupled to cyclic adenosine monophosphate (cAMP) production, contributing to the increased cAMP production seen during opioid dependence and withdrawal. Thus, although we agree with previous investigators about the importance of NMDA receptors, we hypothesize that mGluRs also play a critical role in the contribution of excitatory amino acids to opioid tolerance and dependence.

虽然阿片类药物是最常用的镇痛药,但其治疗效果受到长期使用的耐受性和依赖性的限制。许多研究已经检查了阿片类药物耐受性和依赖性发展的可能机制。最近,一些研究小组关注兴奋性氨基酸受体,特别是n -甲基- d -天冬氨酸(NMDA)受体,以及相关的细胞内第二信使系统作为阿片耐受性和依赖性的可能介质。本文提出的假设是这些阿片耐受性和依赖性模型的延伸,表明代谢性谷氨酸受体(mGluRs)在阿片耐受性和依赖性的发展中起关键作用。我们提出,与磷脂酰肌醇(PI)水解正偶联的I组mGluRs(也可能是δ-阿片受体)的活性在慢性吗啡给药期间增加。这最终导致蛋白激酶C的激活增加,伴随着μ-阿片受体的磷酸化(使其脱敏),以及与NMDA受体相关的离子通道(允许增加Ca2+的流入)。我们还认为,II组和III组mGluRs存在异源脱敏,它们与环磷酸腺苷(cAMP)的产生负偶联,导致阿片类药物依赖和戒断期间cAMP的产生增加。因此,尽管我们同意先前研究者关于NMDA受体重要性的观点,但我们假设mGluRs在兴奋性氨基酸对阿片耐受性和依赖性的贡献中也起着关键作用。
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引用次数: 48
Release of glutamate during opioid exposure 阿片类药物暴露期间谷氨酸的释放
Pub Date : 1999-03-01 DOI: 10.1016/S1082-3174(99)70043-7
Tony L. Yaksh , Martin Marsala , Takae Ibuki
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引用次数: 0
The multi-issue nature of sex differences in opioid analgesia 阿片类镇痛中性别差异的多因素性质
Pub Date : 1999-03-01 DOI: 10.1016/S1082-3174(99)70018-8
Gayle Giboney Page

Just as the nature of the pain experience can be affected by many factors, both physiologic and psychological, so can the effectiveness of opioid analgesia. Of the many possibilities, three factors are presented in this commentary in response to the preceding Focus article of Miaskowski and Levine. First, two previous studies reporting male-female differences in opioid consumption found such differences to occur only prior to age 60 to 65, at female menopause, suggesting that sex hormonal status should be considered in studies assessing the efficacy of opioid treatment. Second, given that sex and sex hormonal status have been shown to relate to both human and animal physiologic responses to stress and the likelihood that these responses affect nociceptive mechanisms, it is important to further explore these differences in order to optimize pain intervention strategies. Finally, it is encouraged that researchers strive to incorporate chronobiologic and sex hormonal considerations in future animal studies in an effort to more closely model clinical phenomena in exploring biobehavioral responses to stress, pain, and pain-relieving treatment modalities.

正如疼痛体验的性质可以受到许多因素的影响,包括生理和心理因素,阿片类镇痛的有效性也可以受到影响。在许多可能性中,这篇评论中提出了三个因素,以回应Miaskowski和Levine之前的焦点文章。首先,先前的两项研究报告了阿片类药物消费的男女差异,发现这种差异只发生在60至65岁之前,即女性更年期,这表明在评估阿片类药物治疗效果的研究中应考虑性激素状况。其次,考虑到性别和性激素状态已被证明与人类和动物对应激的生理反应以及这些反应影响伤害感知机制的可能性有关,进一步探索这些差异以优化疼痛干预策略是很重要的。最后,鼓励研究人员在未来的动物研究中结合时间生物学和性激素因素,以更紧密地模拟临床现象,探索生物行为对压力,疼痛和缓解疼痛的治疗方式的反应。
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引用次数: 6
Cellular and molecular mechanisms of opioid tolerance and dependence 阿片类药物耐受和依赖的细胞和分子机制
Pub Date : 1999-03-01 DOI: 10.1016/S1082-3174(99)70017-6
Keith A. Trujillo

Recent cellular models of opioid tolerance and dependence have incorporated the idea that excitatory amino acid systems may have an important role in these phenomena. Fundytus and Coderre have developed a model that suggests a prominent role for metabotropic glutamate receptors in the initiation and the development of opioid tolerance and dependence. This Commentary briefly reviews Fundytus and Coderre's model of tolerance and dependence, offering comparisons and contrasts with the model of Mao, Price, and Mayer, which suggests a central role for N-methyl-D-aspartate receptors. Strengths and weaknesses of these models are discussed, as well as potential revisions that may lead to a more complete model of these phenomena.

最近的阿片类药物耐受和依赖的细胞模型已经纳入了兴奋性氨基酸系统可能在这些现象中起重要作用的想法。Fundytus和Coderre建立了一个模型,表明代谢性谷氨酸受体在阿片耐受性和依赖性的开始和发展中起着重要作用。讨论了这些模型的优点和缺点,以及可能导致这些现象的更完整模型的潜在修订。
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引用次数: 21
Does opioid analgesia show a gender preference for females? 阿片类镇痛是否对女性有性别偏好?
Pub Date : 1999-03-01 DOI: 10.1016/S1082-3174(99)70044-9
Christine Miaskowski , Jon D. Levine

Recent evidence suggests that one of the factors that may influence the assessment and management of pain is a person's gender. However, only a limited amount of information exists on gender differences in responses to analgesic medications. Based on a review of the available literature published between 1966 and 1998, we suggest that opioids are better analgesics for women. The information in this paper comes predominantly from several studies on the use of patient-controlled analgesia for the management of postoperative pain. Additional information comes from our recent work that demonstrated a sexual dimorphism in oral surgery patients' responses to three different opioid analgesics that share the property of acting as agonists at the kappa-opioid receptor. The paper concludes with a discussion of the major recommendations for future research regarding the gender biology of pain.

最近的证据表明,可能影响疼痛评估和管理的因素之一是一个人的性别。然而,只有有限的信息存在于镇痛药物反应的性别差异。基于对1966年至1998年间发表的现有文献的回顾,我们认为阿片类药物对女性来说是更好的镇痛药。在这篇论文的信息主要来自几个研究使用病人控制镇痛的管理术后疼痛。我们最近的研究表明,口腔手术患者对三种不同的阿片镇痛药的反应存在性别二态性,这三种阿片镇痛药在kappa-阿片受体中具有激动剂的作用。本文最后讨论了关于疼痛的性别生物学未来研究的主要建议。
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引用次数: 89
Mechanisms of opioid tolerance 阿片耐受性的机制
Pub Date : 1999-03-01 DOI: 10.1016/S1082-3174(99)70014-0
David J. Mayer, Jianren Mao

This Commentary evaluates several observations and hypotheses made by Fundytus and Coderre: (1) Initial treatment with high doses of μ-opioid agonists decrease phosphatidlylinositol (PI) hydrolysis, while (2) chronic treatment increases PI hydrolysis to near control levels via increased activity of type I metabotropic glutamate receptors (mGluRs) and/or δ-opioid receptors. (3) The resulting inositol 1,4,5-trisphosphate-mediated increase in protein kinase C then phosphorylates a μ-opioid coupled G-protein, leading to a desensitization of μ-opioid receptors; phosphorylates N-methyl-D-aspartate (NMDA) receptor-associated Ca2+ channels, resulting in a release of these channels from an Mg2+ block; and increases Ca2+/calmodulin-dependent protein kinase, which produces additional phosphorylation of μ-opioid coupled G-protein, leading to further desensitization of μ-opioid receptors. (4) A role for type II/III mGluRs in opioid dependence occurs from desensitization of these receptors, which allows 3′,5′-cyclic adenosine monophosphate to remain at levels high enough to produce withdrawal symptoms. (5) Second messenger systems interact. We then review some of the observations with which a model of opioid tolerance should be consistent. Finally, we review a model for opioid tolerance that we recently proposed.

这篇评论对Fundytus和Coderre提出的几个观察和假设进行了评估:(1)高剂量μ-阿片受体激动剂的初始治疗减少了磷脂酰肌醇(PI)的水解,而(2)慢性治疗通过增加I型代谢型谷氨酸受体(mGluRs)和/或δ-阿片受体的活性,使PI水解接近控制水平。(3)肌醇1,4,5-三磷酸介导的蛋白激酶C的增加使μ-阿片偶联g蛋白磷酸化,导致μ-阿片受体脱敏;磷酸化n -甲基- d -天冬氨酸(NMDA)受体相关的Ca2+通道,导致这些通道从Mg2+阻滞中释放;增加Ca2+/钙调素依赖性蛋白激酶,使μ-阿片样物质偶联g蛋白磷酸化,导致μ-阿片样物质受体进一步脱敏。(4) II/III型mGluRs在阿片类药物依赖中的作用源于这些受体的脱敏,这使得3 ',5 ' -环腺苷单磷酸保持在足以产生戒断症状的高水平。(5)第二信使系统相互作用。然后,我们回顾了一些与阿片类药物耐受性模型应该一致的观察结果。最后,我们回顾了我们最近提出的阿片类药物耐受性模型。
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引用次数: 20
Pathophysiology of acute herpes zoster and postherpetic neuralgia 急性带状疱疹和带状疱疹后神经痛的病理生理学研究
Pub Date : 1998-12-01 DOI: 10.1016/S1082-3174(98)80010-X
Turo Nurmikko
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引用次数: 3
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