We evaluated the role of
serotonin (5-HT) in neoplastic cord compression in paraplegic rats harboring a thoracolumbar
epidural tumor. We measured
serotonin and its major metabolite, 5-hydroxyindole-3-acetic
acid (5-HIAA), in the C-1 to C-7, T-1 to T-6, T-7 to T-12, and T-13 to
L-3 spinal segments of
tumor-free and
tumor-bearing rats. In normal controls, a consistent rostral-to-caudal gradient for
5-HT and
5-HIAA was evident, but the 5-HIAA/5-HT ratio remained constant. In paralyzed rats,
5-HT levels were unchanged, but the 5-HIAA/5-HT ratio was elevated, especially in the compressed segments. Treatment with either
dexamethasone or
indomethacin delayed onset of
paraplegia but had no effect on
5-HT metabolism. Blocking
5-HT receptors by
cyproheptadine, evaluated 30 hours after onset of
paralysis and treatment, resulted in a reduction in the high water content, vascular permeability, and
prostaglandin E2 synthesis in the compressed cord. Early administration of
cyproheptadine effectively delayed the onset of
paraplegia. These data indicate that receptor-activated serotonergic mechanisms participate in the disruption of the blood-spinal cord barrier and that these effects can be manipulated pharmacologically.