Laboratory of Neuroimmunology and Behavior, Department of Neuroscience, School of Behavioral and Brain Sciences, Center for Advanced Pain Studies (CAPS), University of Texas at Dallas, 800 W. Campbell Road, Richardson, TX, 75080, USA.
Sci Rep. 2022 Sep 1;12(1):14840. doi: 10.1038/s41598-022-18281-x.
Understanding the interactions between diet, obesity, and diabetes is important to tease out mechanisms in painful pathology. Western diet is rich in fats, producing high amounts of circulating bioactive metabolites. However, no research has assessed how a high-fat diet (HFD) alone may sensitize an individual to non-painful stimuli in the absence of obesity or diabetic pathology. To investigate this, we tested the ability of a HFD to stimulate diet-induced hyperalgesic priming, or diet sensitization in male and female mice. Our results revealed that 8 weeks of HFD did not alter baseline pain sensitivity, but both male and female HFD-fed animals exhibited robust mechanical allodynia when exposed to a subthreshold dose of intraplantar Prostaglandin E (PGE) compared to mice on chow diet. Furthermore, calcium imaging in isolated primary sensory neurons of both sexes revealed HFD induced an increased percentage of capsaicin-responsive neurons compared to their chow counterparts. Immunohistochemistry (IHC) showed a HFD-induced upregulation of ATF3, a neuronal marker of injury, in lumbar dorsal root ganglia (DRG). This suggests that a HFD induces allodynia in the absence of a pre-existing condition or injury via dietary components. With this new understanding of how a HFD can contribute to the onset of pain, we can understand the dissociation behind the comorbidities associated with obesity and diabetes to develop pharmacological interventions to treat them more efficiently.
了解饮食、肥胖和糖尿病之间的相互作用对于揭示疼痛病理中的机制非常重要。西方饮食富含脂肪，会产生大量循环生物活性代谢物。然而，目前还没有研究评估高脂肪饮食（HFD）单独在没有肥胖或糖尿病病理的情况下如何使个体对非疼痛刺激敏感。为了研究这一点，我们测试了 HFD 刺激饮食诱导性痛觉过敏预激或饮食敏化的能力，在雄性和雌性小鼠中进行了测试。我们的结果表明，8 周的 HFD 不会改变基线疼痛敏感性，但与喂食标准饮食的小鼠相比，雄性和雌性 HFD 喂养的动物在暴露于亚阈值剂量的足底前列腺素 E（PGE）时均表现出明显的机械性痛觉过敏。此外，对两性分离的初级感觉神经元进行钙成像显示，与标准饮食相比，HFD 诱导了更多的辣椒素反应神经元。免疫组织化学（IHC）显示 HFD 诱导了背根神经节（DRG）中损伤的神经元标志物 ATF3 的上调。这表明，HFD 通过饮食成分在没有预先存在的疾病或损伤的情况下引起痛觉过敏。通过对 HFD 如何引发疼痛的新理解，我们可以了解肥胖和糖尿病相关并发症背后的分离，从而开发出更有效的药物干预措施来治疗它们。
