The Neurotoxicity of Drugs Given Intrathecally (Spinal)

Abstract

A growing understanding of the neuropharmacology of spinal cord processing of nociceptive input has led to intense interest in the use of spinal drugs in anesthesia and pain management. The direct application of receptor-specific therapeutics at the spinal cord can potentially interrupt specific pain pathways and limit systemic side effects, but this practice also carries the inherent risk of injury to the central nervous system. Thus, the neurotoxicity of spinal drugs is a central safety issue. Spinal cord or nerve root toxicity may manifest itself as histologic, physiologic, or behavioral/clinical derangements after exposure to a spinal drug. Neurohistopathology is broadly classified as neural injury, gliosis, or damage to the myelin sheath, and it also describes inflammatory changes and involvement of the arachnoid cell layers. Physiologic neurotoxicity of spinal drugs includes changes in spinal cord blood flow, disruption of the blood-brain barrier, and changes in the electrophysiology of impulse conduction. Behavioral and clinical signs of neurotoxicity include pain, motor and sensory deficits, and bowel and bladder dysfunction. Ideally, a complete roster of histological, physiologic, and behavioral testing would be performed on spinal drugs in several animal species, followed by safety trials in humans before widespread use. In practice, drugs have taken a variety of roads from conception to application, and often without safety data. In this article, we review available neurotoxicity data on drugs that have a clinical application, classified as spinal local anesthetics, spinal analgesics, or spinal adjuvants.