The role of cyclooxygenase-2 and inflammatory cytokines in pain induction of herniated lumbar intervertebral disc.

Lumbar disc herniation (LDH) is the disease which is the major cause of radiculopathy. In terms of the pathogenesis of disease, it is reported that prostaglandinE2 (PGE2) plays an important role to induce radiculopathy. Arachidonate cascade, which is the process of PGE2 synthesis, is mainly regulated by two kinds of enzymes, phospholipaseA2 (PLA2) and cyclooxy genase (COX). Previously, PLA2 was recognized as the rate-limiting enzyme of this cascade, and some authors reported the clinical significance of PLA2 at the site of LDH concerning the radicular pain. Recently, COX was elucidated to consist of 2 types of isoform, a constitutive form of COX-1 and an inducible form of COX-2. COX-2 has been focused as a key enzyme to regulate PGE2 synthesis and plays an important role in inflammation, because COX-2 was induced in many types of cells by the stimulation of inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha). However, it is not fully discussed whether or not, COX-2 is induced in lumbar disc tissue and if it plays a significant role in the pathogenesis of LDH. To clarify the role of COX-2 in the pathomechanism of radiculopathy of LDH, we have investigated the expression of COX-2, IL-1 beta and TNF alpha in herniated lumbar disc tissue. Immunohistologically, they were detected in the cytosol of chondrocytes constituting the disc tissue. RT-PCR showed that herniated lumbar disc-derived cells expressed mRNA of COX-2, IL-1 beta and TNF alpha in the presence of inflammatory cytokines in vitro. The disc-derived cells also produced much PGE2 by stimulating of inflammatory cytokines at the same time and this PGE2 production was distinctly suppressed by a selective inhibitor of COX-2, 6-methoxy-2-naphtyl acetic acids (6MNA). These results suggest that COX-2 and inflammatory cytokines might play a causative role in the radiculopathy of LDH through upregulating PGE2 synthesis.