In vivo mechanical loading and tissue adaptation in vertebrae: Inflammation, pain and opioid effects

椎骨的体内机械负荷和组织适应：炎症、疼痛和阿片类药物的作用

• 批准号: 464432349
• 负责人: Dr. Melih Özgür Celik, since 5/2023
• 金额: --
• 依托单位: Julius Wolff Institut für Biomechanik und Muskuloskeletale Regeneration (CVK)
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/464432349?language=en
• 关键词: vivo; mechanical; loading; tissue; adaptation

To allow for mechanistic analyses of the interplay of lumbar spine morphology, mechanical loading and movement on the one side and resulting inflammation and pain on the other, we will use an in vivo mouse model. We will employ an established vertebral loading protocol that allows axial compression of the spine exposed to different shapes, identify the local tissue and inflammatory reaction and – for the first time – modulate pain by opioid receptor activation. Using longitudinal in vivo imaging (µCT) and histomorphometric analysis, we will investigate how spine loading (for 2 weeks, 5 days/week) impacts tissue morphology across spinal segments (cortical, trabecular and disc structures) and whether it influences inflammatory mediators (protons, radicals) and neuropeptides (opioids, substance P) in these and corresponding tissues (spinal cord, dorsal root ganglia) as well as the resulting local immune compartments in the bone marrow. By enforcing the elementary shapes (I-IV) defined by Roussouly et al., we aim to determine how shapes influence tissue adaptation under compression and to what degree such adaptation could be “rescued” after releasing the constrained shapes and by pain modulation. With this approach, we aim to achieve a mechanistic understanding of how musculoskeletal spine tissues adapt to mechanical loading and how this load-induced pain can be modulated. We hypothesize that mechanical loading induces tissue and immune compartment modulations that can be compensated by a local activation of opioid receptors.

为了能够对腰椎形态、一侧的机械负荷和运动以及另一侧导致的炎症和疼痛的相互作用进行力学分析，我们将使用活体小鼠模型。我们将采用一种既定的脊椎加载方案，允许对暴露在不同形状下的脊柱进行轴向压缩，识别局部组织和炎症反应，并首次通过阿片受体激活来调节疼痛。使用体内纵向成像(µCT)和组织形态计量学分析，我们将研究脊柱负荷(2周、5天/周)如何影响脊柱节段(皮质、小梁和椎间盘结构)的组织形态，以及它是否影响这些组织和相应组织(脊髓、背根神经节)中的炎症介质(质子、自由基)和神经肽(阿片类物质，P物质)以及由此产生的骨髓局部免疫间隔。通过实施RousSouly等人定义的基本形状(I-IV)，我们的目标是确定形状如何影响压缩下的组织适应，以及在释放受限制的形状和疼痛调制后，这种适应可以在多大程度上被“拯救”。通过这种方法，我们的目标是实现对肌肉骨骼脊柱组织如何适应机械负荷以及如何调节这种负荷引起的疼痛的机械理解。我们假设，机械负荷诱导组织和免疫间隔调节，这种调节可以通过阿片受体的局部激活来补偿。