Dorsal root ganglion response to intervertebral disc degenerative environment (NEURODISC2)

ARI Exploratory Research

J Ma, S Grad, M Peroglio, M Alini

Background

Low back and neck pain have been repeatedly reported as leading causes of disability worldwide. Back pain can have many different origins and is therefore difficult to treat, especially in the case of chronic back pain. Intervertebral disc (IVD) degeneration is one of the major causes, with a correlation between degeneration and pain. It has been demonstrated that disc degeneration impacts the adjacent nervous system structures, such as the nerve roots or the dorsal root ganglion (DRG). Consequently, DRG may become more sensitive to nociceptive stimuli and spontaneous activation resulting in a nonfunctional response. Moreover, IVD degeneration can also lead to neural plasticity and an ingrowth of nerve fibers into deeper layers of the anulus fibrosus. A better understanding the link between IVD degeneration and pathological change in the sensory nervous system may help to develop novel therapies against back pain. 

 

 

Goal

The project aimed to study how the degenerative IVD influences dorsal root ganglion (DRG) and spinal cord glia using in vitro and ex vivo models in order to better understand the link between IVD degeneration and pain.

 

Results

DRG primary cell and DRG organ cultures were established from various species. We found that stress factors commonly observed in degenerative IVD, like hypoxia and low glucose, contribute to aberrant neurite sprouting. This was consistently observed in the DRG cell line ND7/23, DRG primary cells and explant culture models. Moreover, hypoxia and acidosis induced a higher spontaneous and bradykinin-stimulated calcium response compared to normoxia and neutral pH cultures, suggesting that these factors could be implicated in the development of spontaneous and inflammatory pain. 


  • Presentation

    Ma J, Stefanoska D, Grad S, Alini M, Peroglio M. Hypoxia and low pH stressed disc conditioned medium promotes hypersensitivity of peripheral sensory neurons. ORS PSRS 5th Symposium, Skytop PA (US), Nov 3-7, 2019 (poster).

    Stefanoska D, Ma J, Grad S, Alini M, Peroglio M. Effects of glucose concentration and pH on dorsal root ganglion neurite outgrowth. Pain in EU XI EFIC, Valencia (Spain), Sep 4-7, 2019 (e-poster).

    Ma J, Stefanoska D, Grad S, Alini M, Peroglio M. Effect of pH and oxygen tension on dorsal root ganglion calcium response to bradykinin and neurite sprouting. Pain in EU XI EFIC, Valencia (Spain), Sept 4-7, 2019 (poster).

    Ma J, Stefanoska D, Hildebrand M, Zeiter S, Alini M, Peroglio M. Validation of cell line models to study intervertebral disc neo-innervation associated with discogenic pain. Swiss 3R Day, Bern (CH), Sept 2, 2019 (poster).

    Ma J, Stefanoska D, Grad S, Alini M, Peroglio M. Low pH culture of dorsal root ganglion cells as an in vitro model to study pathological changes involved in the development of neuropathic pain. 7th International Congress on Neuropathic Pain, London (UK), May 9-11, 2019 (poster).

    Ma J, Stefanoska D, Grad S, Alini M, Peroglio M. Hypoxic stress enhances extension and branching of sensory neuronal outgrowth: a comparison between in vitro and ex vivo model. 7th International Congress on Neuropathic Pain, London (UK), May 9-11, 2019 (poster).

  • Partner

    Häckel S (MD), Orthopaedics Department, Inselspital, University of Bern, Switzerland

    Pandit A (Prof), Centre for Research in Medical Devices (CÚRAM), National University of Ireland, Galway

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