Departments of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas.
Departments of Neurosurgery, University of Kansas Medical Center, Kansas City, Kansas.
J Pain. 2018 Nov;19(11):1285-1295. doi: 10.1016/j.jpain.2018.05.005. Epub 2018 May 25.
Pain is significantly impacted by the increasing epidemic of obesity and the metabolic syndrome. Our understanding of how these features impact pain is only beginning to be developed. Herein, we have investigated how small genetic differences among C57BL/6 mice from 2 different commercial vendors lead to important differences in the development of high-fat diet-induced mechanical sensitivity. Two substrains of C57BL/6 mice from Jackson Laboratories (Bar Harbor, ME; C57BL/6J and C57BL/6NIH), as well as C57BL/6 from Charles Rivers Laboratories (Wilmington, MA; C57BL/6CR) were placed on high-fat diets and analyzed for changes in metabolic features influenced by high-fat diet and obesity, as well as measures of pain-related behaviors. All 3 substrains responded to the high-fat diet; however, C57BL/6CR mice had the highest weights, fat mass, and impaired glucose tolerance of the 3 substrains. In addition, the C57BL/6CR mice were the only strain to develop significant mechanical sensitivity over the course of 8 weeks. Importantly, the C57BL/6J mice were protected from mechanical sensitivity, which may be based on increased physical activity compared with the other 2 substrains. These findings suggest that activity may play a powerful role in protecting metabolic changes associated with a high-fat diet and that these may also be protective in pain-associated changes as a result of a high-fat diet. These findings also emphasize the importance of selection and transparency in choosing C57BL/6 substrains in pain-related research. PERSPECTIVE: Obesity and the metabolic syndrome play an important role in pain. This study identifies key differences in the response to a high-fat diet among substrains of C57BL/6 mice and differences in intrinsic physical activity that may influence pain sensitivity. The results emphasize physical activity as a powerful modulator of obesity-related pain sensitivity.
疼痛受肥胖症和代谢综合征流行的影响显著。我们对这些特征如何影响疼痛的理解才刚刚开始。在此，我们研究了来自 2 个不同商业供应商的 C57BL/6 小鼠之间的微小遗传差异如何导致高脂肪饮食诱导的机械敏感性发展中的重要差异。来自杰克逊实验室（缅因州巴港；C57BL/6J 和 C57BL/6NIH）的 2 个 C57BL/6 亚系以及来自查尔斯河实验室（马萨诸塞州威尔明顿；C57BL/6CR）的 C57BL/6 被置于高脂肪饮食中，并分析了受高脂肪饮食和肥胖影响的代谢特征变化，以及与疼痛相关的行为测量。所有 3 个亚系均对高脂肪饮食有反应；然而，C57BL/6CR 小鼠的体重、脂肪量和葡萄糖耐量受损程度在 3 个亚系中最高。此外，C57BL/6CR 小鼠是唯一在 8 周内发展出显著机械敏感性的品系。重要的是，C57BL/6J 小鼠对机械敏感性具有保护作用，这可能是由于与其他 2 个亚系相比，其活动量增加所致。这些发现表明，活动可能在保护与高脂肪饮食相关的代谢变化方面发挥强大作用，并且由于高脂肪饮食，这些变化也可能对与疼痛相关的变化具有保护作用。这些发现还强调了在与疼痛相关的研究中选择和透明性在选择 C57BL/6 亚系方面的重要性。观点：肥胖症和代谢综合征在疼痛中起着重要作用。本研究确定了 C57BL/6 小鼠亚系对高脂肪饮食的反应以及内在体力活动的差异，这些差异可能影响疼痛敏感性。结果强调了体力活动作为肥胖相关疼痛敏感性的强大调节剂。
