Toxicology of baclofen continuously infused into the spinal intrathecal space of the dog.
The continuous spinal administration of baclofen has been shown to have therapeutic benefit in the management of spasticity in humans with neuraxial injuries. The present study systematically investigated the potential spinal neurotoxicity of continuous intrathecally-infused baclofen in dogs. Male beagle dogs were prepared with chronic lumbar intrathecal 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 micrograms/ml/24 hrs baclofen (N = 10) or 2000 micrograms/ml/24 hrs baclofen (N = 10). A mild, dose-dependent anti-nociception and muscle weakness was observed. Independent assessment of spinal histopathology 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 ascribed to any dose of intrathecal baclofen. Cisternal CSF protein and cells in samples taken at sacrifice were also not different for the three groups. These findings with chronic intrathecally administered baclofen in this dog model jointly support the lack of toxicity of chronic intrathecal baclofen at concentrations up to 2000 micrograms/ml.
Sabbe
M B
MB
Department of Anesthesiology, University of California, San Diego, La Jolla 92093-0818.
Grafe
M R
MR
Pfeifer
B L
BL
Mirzai
T H
TH
Yaksh
T L
TL
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001418:Baclofen / Q000097:blood / Q000134:cerebrospinal fluid / Q000633:toxicity*; D002319:Cardiovascular System / Q000187:drug effects; D003672:Defecation / Q000187:drug effects; D004285:Dogs; D007263:Infusions, Parenteral; D008161:Lumbosacral Region; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000503:physiopathology; D011388:Prolactin / Q000097:blood; D012119:Respiration / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013346:Subarachnoid Space; D014554:Urination / Q000187:drug effects
D011388:Prolactin; D001418:Baclofen