In Zucker Diabetic Fatty Rats, Subclinical Diabetic Neuropathy Increases In Vivo Lidocaine Block Duration But Not In Vitro Neurotoxicity

Background and Objectives: Application of local anesthetics may lead to nerve damage. Increasing evidence suggests that risk of neurotoxicity is higher in patients with diabetic peripheral neuropathy. In addition, block duration may be prolonged in neuropathy. We sought to investigate neurotoxicity in vitro and block duration in vivo in a genetic animal model of diabetes mellitus type 2. Methods: In the first experiments, neurons harvested from control Zucker diabetic fatty (ZDF) rats were exposed to acute (24 hours) or chronic (72 hours) hyperglycemia, followed by incubation with lidocaine 40 mM (approximately 1%). In a second experiment, neurons harvested from control ZDF rats, or diabetic ZDF rats, were incubated with lidocaine, with or without SB203580, an inhibitor of the p38 mitogen-activated protein kinase. Finally, we performed sciatic nerve block (lidocaine 2%, 0.2 mL) in control or diabetic ZDF rats and measured motor and nociceptive block duration. Results: In vitro, neither acute nor chronic hyperglycemia altered neurotoxic properties of lidocaine. In vitro, incubation of neurons with lidocaine resulted in a slightly decreased survival ratio when neurons were harvested from diabetic (57% +/- 19%) as compared with control (64% +/- 9%) rats. The addition of SB203580 partly reversed this enhanced neurotoxic effect and raised survival to 71% +/- 12% in diabetic neurons and 66% +/- 9% in control rats, respectively. In vivo, even though no difference was detected at baseline testing, motor block was significantly prolonged in diabetic as compared with control rats (137 +/- 16 vs 86 +/- 17 min). Conclusions: In vitro, local anesthetic neurotoxicity was more pronounced on neurons from diabetic animals, but the survival difference was small. In vivo, subclinical neuropathy leads to substantial prolongation of block duration. We conclude that early diabetic neuropathy increases block duration, whereas the observed increase in toxicity was small