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.