gms | German Medical Science

Objectives: A better understanding on the underlying causes of lower back pain represents a broad medical need with increasing numbers not only in elderly but also young patients [1]. While our consortium (FOR 5177) focuses on unraveling the causal links between spine morphology, mechanics and motion in lower back patients and how these are linked to pain, a more mechanistic insight may be challenging to gain in human patient cohort analyses. We could show earlier that bone structures remodel towards mechanical stimuli and that such adaptation can be spatially resolved and linked to an increase in osteoblastic activities and a reduction of osteoclasts [2]. Further, we could show that the bone marrow compartment can be reprogrammed towards a more naïve phenotype by mechanical stimulation [3]. Here, we want to test the hypothesis if such adaptations in long bone are also valid in the mouse tail as a model of the human spine. We aim to link such adaptations of mesenchymal tissues to the ones of the marrow and specifically pain cell surface receptors.

Methods: Female C57BL/6 mice (10 weeks) were divided into two groups with a straight loaded tail and a sham-loaded group. Vertebrae 5 and 7 of the mouse tail were pinned with titan pins through which loading was applied by cyclic axial pressure at 10 Hz for 5 minutes per day 3 times a week over a period of four weeks. Changes in mineral structure were longitudinally monitored using a µCT (MILabs, U-CT xuhr). The bone marrow compartment was analyzed by flow cytometry for characterization of the immune cell composition [3].

Results and conclusion: We expect an increase in bone mass resulting from higher osteoblast activity as well as a shift in the immune cell composition in the bone marrow to a more naïve phenotype. Biggest changes are expected in the myeloid cells, especially monocytes, macrophages and granulocytes. Proofing that the results from mechanical loaded long bones are also applicable for irregular vertebral bodies is one major goal of the project. To narrow down the approach of the immunce cells we have a parallel study ongoing in patients with chronic lower back pain. Detecting expressed opioid receptors on immune cells in those samples will support former in vitro studies from Celik et. al. and the detected subpopulations of the immune cells will be used as a reference for our analyses in the mice model.

The results from the patients on how the immune cell composition changes during lower back pain serves for future translational implementation of our animal experiments and makes the approach of a drug target more feasible. Analyzing the changes in bone mass and immune cells after load was applied will guide a targeted approach for pain diagnosis and treatment in lower back pain. The ultimate goal of peripheral analgesia without systemic side effects is of great necessity.