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

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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.