INTRODUCTION: Low back pain is a clinical problem that results in physical disability and decreased productivity. One of the possible mechanisms of low back pain has been considered that peripheral nerve fibers invade into the degenerated intervertebral disk (IVD) in nerve growth factor (NGF) dependent manner. Although selective COX‐2 inhibitor has been used for treating those patients trying to inhibit PGE2 production to decrease the risk of the acute pain, its effect on NGF regulation in IVD has been unclear. The role of PGE2 on the regulation of NGF in IVD cells was investigated.
METHODS: Confluent IVD cells were pre‐incubated with selective COX‐2 inhibitor (NS‐398), prostaglandin E2 (PGE2) or steroid (dexamethasone (Dex)) for 30 min and then stimulated with interleukin‐1 (IL‐1) (10 ng/ml) for a further 24 hours. The expression of NGF and COX‐2 mRNA was quantified by real time‐PCR.
RESULTS: IL‐1 stimulated the expression of NGF and COX‐2 in IVD cells. The induction of both NGF and COX‐2 was strongly inhibited by Dex. Treating the cells with NS‐398 did not affect the expression of COX‐2 whereas it augmented the IL‐1 induction of NGF expression. Conversely, exogenous PGE2 treatment resulted in the suppression of IL‐1‐induced NGF expression.
DISCUSSION: Selective COX‐2 inhibitors have been widely used in clinical treatment for patients with low back pain and have been beneficial for acute pain. Hence, our data revealed that selective COX‐2 inhibitor augmented the expression of NGF in response to inflammatory stimuli such as IL‐1, suggesting that this treatment may lead chronic low back pain. In addition, suppression of NGF expression by exogenous PGE2 may indicate that PGE2 play a negative feedback for NGF expression in IVD cells.