The Role of Cytokines in the Degenerative Spine

Abstract

The intervertebral disc has traditionally been regarded as a biomechanically important structure in the spine, with characteristic biomechanical properties related to both the annulus fibrosus and the nucleus pulposus. However, research performed mainly during the last 15 years has revealed that the intervertebral disc is also biologically active and that, for example, the pathophysiology of disc degeneration and herniation is related to the production by disc cells of substances such as pro-inflammatory cytokines, for example, TNF and various interleukins. It has been shown that herniated cervical and lumbar disc specimens spontaneously produce increased amounts of various substances, such as nitrix oxide, interleukin-6, prostaglandin E2 and certain matrix metalloproteinases. Furthermore, the cells of intervertebral discs are biologically responsive and increase their production in vitro of these substances even more when stimulated by interleukin-1 beta. Increased levels of interleukin-6 and interleukin-8 have been found in disc specimens from patients with discogenic low back pain, indicating a possible role of such substances in the pathogenesis of low back pain. Increased levels of pro-inflammatory cytokines such as interleukin-1 beta have been found in facet joint tissues in patients undergoing surgery for lumbar spinal stenosis and disc herniation. These observations suggest the involvement of pro-inflammatory cytokines as a factor in the genesis of pain production in degenerated lumbar facet joints. The pathophysiology of sciatic pain, in association with disc herniation, has been shown to be related to a combination of biochemical nerve root irritation via pro-inflammatory cytokines such as TNF, produced by nucleus pulposus cells and mechanical nerve root compression. The cytokine mediated nerve root inflammation induces a sensitization of the nerve root so that the mechanical nerve root compression leads to radiating sciatic pain. Animal experimental studies have shown that anti-TNF substances, e.g. infliximab and etanercept, can reduce or prevent TNF induced nerve root changes, as well as pain behavioural reactions. Initial clinical studies have indicated a possible role of anti-TNF treatment in patients with sciatica and lumbar disc herniation, but recent studies have provided contradictory results. Further clinical studies in this field are in progress. In conclusion, there is a large body of evidence indicating that pro-inflammatory cytokines and other related substances play important roles in the pathophysiology of various spinal pain conditions.