Sex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neurons.
Sex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neurons.
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DOI：
10.1038/s41598-023-31603-x
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发表时间：
2023-03-22
影响因子：
4.6
通讯作者：
Tavares-Ferreira, Diana
中科院分区：
文献类型：
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作者：
Shen, Breanna Q. Q.;Sankaranarayanan, Ishwarya;Price, Theodore J.;Tavares-Ferreira, Diana
越来越多的证据表明，在临床前模型和临床人群中，导致疼痛的潜在机制存在性别差异。临床疼痛人群和临床前疼痛研究的进行方式之间也存在重要的脱节。例如，骨关节炎疼痛更多地影响女性，但大多数临床前研究都是在动物模型中使用男性进行的。最广泛使用的止痛药，非类固醇抗炎药(NSAIDs)，通过抑制环氧合酶(COX)酶来作用于前列腺素途径。本研究的目的是分析前列腺素和环氧合酶在炎症和疼痛中的作用的临床前和临床文献。我们的目标是明确使用两种性别的研究，并调查是否在临床或临床前研究中前列腺素和环氧合酶抑制的作用存在性别差异。我们进行了PubMed搜索，确定了369项临床前研究和100项临床研究，这些研究符合我们的纳入/排除标准。我们的分析表明，只有17%的前列腺素临床前研究使用了两性，其中只有19%按性别分析或报告了数据。相比之下，79%的临床研究同时使用了两种性别。然而，在这些报告的数据中，只有6%按性别分类。有趣的是，15项临床前研究中的14项和6项临床研究中的5项分析了按性别分开的数据，发现了性别差异。这是建立在越来越多的证据表明前列腺素信号的性别差异以及性别作为生物变量在数据分析中的重要性的基础上的。临床前文献证实，在神经系统中，雌性啮齿动物的前列腺素D2合成酶(PTGDS)的表达高于雄性啮齿动物。我们从实验上证实，PTGDS在从器官捐赠者那里恢复的女性人背根神经节(DRG)神经元中的表达更高。我们的半系统文献回顾显示，在前列腺素研究和临床前和临床研究中按性别分开的数据分析中，需要继续包括雄性和雌性动物。我们在人类神经元PTGDS表达上的性别差异表明，需要更全面地了解前列腺素系统如何在啮齿动物和人类的DRG中发挥作用。
There is increasing evidence of sex differences in underlying mechanisms causing pain in preclinical models, and in clinical populations. There are also important disconnects between clinical pain populations and the way preclinical pain studies are conducted. For instance, osteoarthritis pain more frequently affects women, but most preclinical studies have been conducted using males in animal models. The most widely used painkillers, nonsteroidal anti-inflammatory drugs (NSAIDs), act on the prostaglandin pathway by inhibiting cyclooxygenase (COX) enzymes. The purpose of this study was to analyze the preclinical and clinical literature on the role of prostaglandins and COX in inflammation and pain. We aimed to specifically identify studies that used both sexes and investigate whether any sex-differences in the action of prostaglandins and COX inhibition had been reported, either in clinical or preclinical studies. We conducted a PubMed search and identified 369 preclinical studies and 100 clinical studies that matched our inclusion/exclusion criteria. Our analysis shows that only 17% of preclinical studies on prostaglandins used both sexes and, out of those, only 19% analyzed or reported data separated by sex. In contrast, 79% of the clinical studies analyzed used both sexes. However, only 6% of those reported data separated by sex. Interestingly, 14 out of 15 preclinical studies and 5 out of 6 clinical studies that analyzed data separated by sex have identified sex-differences. This builds on the increasing evidence of sex-differences in prostaglandin signaling and the importance of sex as a biological variable in data analysis. The preclinical literature identifies a sex difference in prostaglandin D2 synthase (PTGDS) expression where it is higher in female than in male rodents in the nervous system. We experimentally validated that PTGDS expression is higher in female human dorsal root ganglia (DRG) neurons recovered from organ donors. Our semi-systematic literature review reveals a need for continued inclusivity of both male and female animals in prostaglandins studies and data analysis separated by sex in preclinical and clinical studies. Our finding of sex-differences in neuronal PTGDS expression in humans exemplifies the need for a more comprehensive understanding of how the prostaglandin system functions in the DRG in rodents and humans.
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DOI：
10.1016/j.jchromb.2013.11.041
发表时间：
2014-01-15
影响因子：
3
作者：
Shaik, Jafar Sadik B.;Miller, Tricia M.;Graham, Steven H.;Manole, Mioara D.;Poloyac, Samuel M.
通讯作者：
Poloyac, Samuel M.
影响因子：
3
作者：
Burke, JG;Watson, RWG;Fitzpatrick, JM
通讯作者：
Fitzpatrick, JM
影响因子：
6.9
作者：
Mogil, Jeffrey S.
通讯作者：
Mogil, Jeffrey S.
影响因子：
3.2
作者：
Gottesdiener, K;Mehlisch, DR;Mills, S
通讯作者：
Mills, S
影响因子：
7.4
作者：
通讯作者：
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