Immune Mechanisms and Pain in Intervertebral Disc Degeneration

Intervertebral disc degeneration (IVDD) is a major cause of low back pain and radicular pain, posing significant socio-economic challenges. The intervertebral disc is traditionally viewed as immune-privileged. This privilege is maintained by physical barriers and molecular factors such as Fas ligand. However, when these barriers are compromised, the nucleus pulposus (NP) can be exposed to the immune system. Recent evidence underscores a critical role for immune cells, particularly macrophages, in IVDD progression. This exposure can trigger an autoimmune response, leading to inflammation that aggravates dorsal root ganglion injury and results in hyperalgesia and pain. This review aims to autoimmunity, adaptive immunity, and the origins of pain in IVDD. We conclude that understanding these immune mechanisms is crucial, as they reveal promising avenues for future targeted immunotherapies.