Brandão Arthur Freitas, Bonet Ivan José Magayewski, Pagliusi Marco, Zanetti Gabriel Gerardini, Pho Nam, Tambeli Cláudia Herrera, Parada Carlos Amilcar, Vieira André Schwambach, Sartori Cesar Renato
Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil.
eScience Institute, University of Washington, Seattle, WA, United States.
Front Neurosci. 2020 Jan 22;13:1453. doi: 10.3389/fnins.2019.01453. eCollection 2019.
Recent findings from rodent studies suggest that high-fat diet (HFD) increases hyperalgesia independent of obesity status. Furthermore, weight loss interventions such as voluntary physical activity (PA) for adults with obesity or overweight was reported to promote pain reduction in humans with chronic pain. However, regardless of obesity status, it is not known whether HFD intake and sedentary (SED) behavior is underlies chronic pain susceptibility. Moreover, differential gene expression in the nucleus accumbens (NAc) plays a crucial role in chronic pain susceptibility. Thus, the present study used an adapted model of the inflammatory prostaglandin E2 (PGE2)-induced persistent hyperalgesia short-term (PH-ST) protocol for mice, an HFD, and a voluntary PA paradigm to test these hypotheses. Therefore, we performed an analysis of differential gene expression using a transcriptome approach of the NAc. We also applied a gene ontology enrichment tools to identify biological processes associated with chronic pain susceptibility and to investigate the interaction between the factors studied: diet (standard diet vs. HFD), physical activity behavior (SED vs. PA) and PH-ST (PGE vs. saline). Our results demonstrated that HFD intake and sedentary behavior promoted chronic pain susceptibility, which in turn was prevented by voluntary physical activity, even when the animals were fed an HFD. The transcriptome of the NAc found 2,204 differential expression genes and gene ontology enrichment analysis revealed 41 biologic processes implicated in chronic pain susceptibility. Taking these biological processes together, our results suggest that genes related to metabolic and mitochondria stress were up-regulated in the chronic pain susceptibility group (SED-HFD-PGE), whereas genes related to neuroplasticity were up-regulated in the non-chronic pain susceptibility group (PA-HFD-PGE). These findings provide pieces of evidence that HFD intake and sedentary behavior provoked gene expression changes in the NAc related to promotion of chronic pain susceptibility, whereas voluntary physical activity provoked gene expression changes in the NAc related to prevention of chronic pain susceptibility. Finally, our findings confirmed previous literature supporting the crucial role of voluntary physical activity to prevent chronic pain and suggest that low levels of voluntary physical activity would be helpful and highly recommended as a complementary treatment for those with chronic pain.
啮齿动物研究的最新发现表明，高脂饮食（HFD）会增加痛觉过敏，且与肥胖状态无关。此外，据报道，针对肥胖或超重成年人的体重减轻干预措施，如自愿体育活动（PA），可促进慢性疼痛患者的疼痛减轻。然而，无论肥胖状态如何，尚不清楚高脂饮食摄入和久坐行为（SED）是否是慢性疼痛易感性的基础。此外，伏隔核（NAc）中的差异基因表达在慢性疼痛易感性中起关键作用。因此，本研究使用了一种适用于小鼠的炎症性前列腺素E2（PGE2）诱导的持续性短期痛觉过敏（PH-ST）模型、高脂饮食和自愿体育活动范式来检验这些假设。因此，我们使用伏隔核的转录组方法对差异基因表达进行了分析。我们还应用了基因本体富集工具来识别与慢性疼痛易感性相关的生物学过程，并研究所研究因素之间的相互作用：饮食（标准饮食与高脂饮食）、体育活动行为（久坐与体育活动）和PH-ST（PGE与生理盐水）。我们的结果表明，高脂饮食摄入和久坐行为会促进慢性疼痛易感性，而自愿体育活动可以预防这种易感性，即使动物喂食高脂饮食也是如此。伏隔核的转录组发现了2204个差异表达基因，基因本体富集分析揭示了41个与慢性疼痛易感性相关的生物学过程。综合这些生物学过程，我们的结果表明，与代谢和线粒体应激相关的基因在慢性疼痛易感性组（SED-HFD-PGE）中上调，而与神经可塑性相关的基因在非慢性疼痛易感性组（PA-HFD-PGE）中上调。这些发现提供了证据，表明高脂饮食摄入和久坐行为会引发伏隔核中与促进慢性疼痛易感性相关的基因表达变化，而自愿体育活动会引发伏隔核中与预防慢性疼痛易感性相关的基因表达变化。最后，我们的研究结果证实了先前文献支持自愿体育活动在预防慢性疼痛中的关键作用，并表明低水平的自愿体育活动作为慢性疼痛患者的辅助治疗将是有益的，并且强烈推荐。
