Indomethacin and dexamethasone treatment in experimental neoplastic spinal cord compression: Part 2. Effect on edema and prostaglandin synthesis

Edema formation and prostanoid production (prostaglandin E₂ (PGE₂), thromboxane B₂ (TXB₂), and 6-keto-prostaglandin F(1α) (6-keto-PGF(1α)) were studied in a model of neoplastic epidural cord compression (NSCC) in rats harboring a thoracolumbar tumor. Tumor-free and tumor-bearing animals were randomized for three treatments at 12-hour intervals with saline, dexamethasone (10 mg/kg i.p.), or indomethacin (10 mg/kg i.p.). Increase in water content was observed only in the compressed lumbar cord segments of paralyzed rats; the cervical and thoracic segments did not differ from controls. The rate of release of prostaglandins was evenly distributed along the spinal segments in tumor-free rats. in tumor-bearing rats, a consistent significant increase in PGE₂ production was found in the compressed lumbar segment in the presence of neurological dysfunction: early (limp tail), P<0.05; paraplegia, P<0.001. A significantly elevated PGE₂ synthesis preceded the increase in water content by 2 to 3 days. A 2-fold increase in TXB₂ was detected in only one of three experiments, and synthesis of 6-keto-PGF(1α) was elevated to 4 times the normal value (P<0.005) in two of three experiments. Dexamethasone failed to inhibit prostaglandin synthesis in the spinal cord of normal controls or paralyzed rats, whereas in non neural tissues (liver, uterus) it reduced synthesis of the three metabolites by at least 50%, thus demonstrating a differential effect on central nervous system (CNS) vs. non-CNS tissues. Dexamethasone also failed to reduce the increased water content of the compressed segments. Indomethacin, on the other hand, reversed the increased water content back to normal values and caused a marked decrease of the three prostanoids in normal as well as in paralyzed rats. Thus, only indomethacin, which significantly inhibited prostanoid production, was also effective in rapidly reducing spinal cord edema. Indomethacin should be further investigated for its usefulness in the early treatment of NSCC in humans.