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.