Kobe Journal of Medical Sciences, 2000

THE ROLE OF CYCLOOXYGENASE-2 AND INFLAMMATORY CYTOKINES IN PAIN INDUCTIＯＮOF HERNIATED LUMBAR INTERVERTEBRAL DISC.

Hiroshi MIYAMOTO*, Ryuichi SAURA*, Toshihiko HARADA, Minoru DOITA*, and Kosaku MIZUNO*

* Department of Orthopaedic Surgery, Kobe University School of Medicine 
** Department of Orthopaedic Surgery, Kakogawa Prefectural Hospital 770. Awazu, Kakogawa-cho. Kakogawa-city, Hyogo, 675-8555. Japan 

Kobe J. Med. Sci. 46, 13-28, April 2000

AB: Lumbar disc herniation (LDH) is the disease which is the major cause　of radiculopathy. In terms of the pathogenesis of disease, it is report 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 cyclooxygenase (COX). Previously, PLA2 was recognized as the rate-limiting enzyme of this cascade, and some authors reported the clinical significance of PLA2 at the sit 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 type　of cells by the stimulation of inflammatory cytokines such as interleukin-I b (IL-Ib) and tumor necrosis factor a (TNFa). 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-Ib and TNFa 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-Ib and TNFa in the presence of inflammatory cytokines in vitro. The disc-derived cells also produced much PGE2 by stimulating of inflammatory cytokines at the same timeand 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.