Potential Role of Mast Cells in Intervertebral Disc Ageing, Herniation Resolution, and Degeneration: Evidence and Lessons Learned from Studies of Mast Cells in Other Connective Tissues

In the body, mast cells are found in the circulation and located in tissues. These immune cells arise in the bone marrow and are often associated with conditions such as allergies and asthma. However, these cells also play roles in other inflammatory reactions, dysregulated wound healing and chronic conditions. Regarding their presence in tissues of the intervertebral disc (IVD), mast cells have been located in the normal nucleus pulposus, and reports indicate mast cell numbers are elevated in IVD degenerative conditions. As the integrity of the IVD is reported to decline with ageing as well as in sciatica and clinically defined degenerative conditions, targeting mast cell function may be a viable conservative treatment option for the ageing IVD in health and disease. This review discusses the possible involvement of mast cells in IVD health and disease, and the rationale for the use of mast cell stabilizers such as ketotifen as potential treatment options for conditions affecting IVD integrity. Such mast cell targeting treatments may be considered alone or in combination with other molecules such as specific proteinase inhibitors impacting proteinases known to be present in the affected tissues, such as MMP-3 and HTRA1. Thus, a multicomponent approach in such treatments may provide effectiveness in inhibiting progressive loss of IVD integrity and function in chronic degenerative conditions or adverse outcomes due to non-resorption of extruded nucleus pulposus in sciatica.