TOXICOLOGY OF BACLOFEN CONTINUOUSLY INFUSED INTO THE SPINAL INTRATHECAL SPACE OF THE DOG

The continuous spinal administration of baclofen has been shown to hav e therapeutic benefit in the management of spasticity in humans with n euraxial injuries. The present study systematically investigated the p otential spinal neurotoxicity of continuous intrathecally-infused bacl ofen in dogs. Male beagle dogs were prepared with chronic lumbar intra thecal catheters connected to subcutaneously implanted infusion pumps. Three groups of dogs received 28 days of infusion of saline (vehicle: 1 ml/24 hrs; N=10), 200 mu g/ml/24 hrs baclofen (N=10) or 2000 mu g/m l/24 hrs baclofen (N=10). A mild, dose-dependent anti-nociception and muscle weakness was observed. Independent assessment of spinal histopa thology in dogs sacrificed and perfusion fixed at 28 days of treatment revealed a mild fibrotic reaction to the catheter, but there were no changes distinguishable from vehicle infused animals which could be as cribed to any dose of intrathecal baclofen. Cisternal CSF protein and cells in samples taken at sacrifice were also not different for the th ree groups. These findings with chronic intrathecally administered bac lofen in this dog model jointly support the lack of toxicity of chroni c intrathecal baclofen at concentrations up to 2000 mu g/ml. (C) 1993 Intox Press, Inc.