Analgesic and neurotoxic effects of intrathecal corticosteroids in rats

Abstract

Background: Despite the widespread use of epidurally administered corticosteroids in the treatment of sciatica and the failure of animal studies to demonstrate neurotoxicity from epidermally administered corticosteroids, controversy remains regarding the mechanism of action as well as the safety of this treatment. The goal of this study was to determine whether spinally administered corticosteroids have any analgesic effects, and whether repeated intrathecal administration causes any neuronal damage to the spinal cord. Methods: Chronic lumbar intrathecal catheters were implanted in rats. Formalin testing was carried out 1 h after the intrathecal administration of 400 μg methylprednisolone sodium succinate, 48 h after intrathecal administration of triamcinolone diacetate 250 μg, or 24 h after the last of a series of four injections of triamcinolone diacetate 250 μg given at 5-day intervals. Histologic sections of multiple levels of spinal cord from the animals receiving repeat intrathecal steroid injections were compared to those from animals that received intrathecal saline at the same intervals. Results: The animals receiving repeated intrathecal triamcinolone diacetate demonstrated mild, statistically significant reduction of pain behavior (hindlimb flinching) during the second but not the first phase of the formalin test when compared to controls. No analgesic effects were demonstrated after methylprednisolone sodium succinate or a single injection of triamcinolone diacetate. Animals that received methylprednisolone sodium succinate demonstrated transient segmental allodynia. No behavioral or neurologic abnormalities were seen in any other group. Some histologic evidence neuronal damage (the presence of argyrophilic neurons was seen in the chronically implanted animals in areas of the cord adjacent to the spinal catheters, but there was no difference in incidence of these changes between the steroid and control groups. Conclusions: Intrathecal steroid injections have no analgesic effect and do not suppress spinal sensitization when administered acutely. After chronic administration, there is a mild effect on nociceptor-driven spinal sensitization (phase 2 of the formalin test), but no analgesic effect on an acute noxious stimulus (phase 1 of the formalin test). Repeated intrathecal administration of triamcinolone diacetate (0.8 mg/kg) is not associated with spinal neurotoxic effects during the time period studied.