Intrathecal lidocaine causes posterior root axonal degeneration near entry into the spinal cord in rats.

ABSTRACT

BACKGROUND AND OBJECTIVES: The neurotoxicity of lidocaine is not fully understood, and the primary lesion of lidocaine-induced spinal neurotoxicity has not been defined. Here we examine the effects of various concentrations of intrathecally administered lidocaine. METHODS: Forty-seven Wistar rats received 20%, 10%, 7.5%, 5%, 3%, or 0% lidocaine dissolved in distilled water, or 25% glucose solution via a chronically implanted intrathecal catheter. The spinal cord at L1, posterior and anterior roots, and cauda equina were dissected out 5 days later, sectioned, and prepared for light and electron microscopy. The effect of the agent on function was evaluated by movement of the hind limb (behavior test) and by sensory threshold (paw stimulation test). Another 7 rats were used to establish the precise locus of lesion within the posterior root after intrathecal 20% lidocaine injection. RESULTS: Rats treated with 10% or 20% lidocaine developed lesions both in the posterior roots and posterior columns, characterized by axonal degeneration. Rats injected with 7.5% lidocaine developed degenerative lesions limited to the posterior roots. Lesions in the posterior roots were localized to the proximal portion of the roots. Injections of 5% or less lidocaine did not cause any pathological changes. One of 5 rats receiving 20% lidocaine showed hind-limb paralysis for 4 days, but the remaining 4 rats recovered within 4 days after drug injection. Rats injected with < or = 10% lidocaine were completely recovered within 4 hours. The threshold for paw stimulation was significantly decreased in rats injected with 20% lidocaine. CONCLUSION: Our results suggest that spinal lidocaine neurotoxicity after supra-clinical concentrations of lidocaine is limited initially to the posterior roots at their entry to the spinal cord, and the extent and severity of the lesions are closely associated with lidocaine concentration. Unlike severe lesions in rats injected with 20% lidocaine, mild lesions caused by lower concentrations may not manifest neurofunctional deficits.