Pain Medicine  |   March 2018
Pharmacodynamics and Pharmacokinetics of Lidocaine in a Rodent Model of Diabetic Neuropathy
Author Notes
  • From the Department of Anesthesiology and Laboratory of Experimental Anesthesiology and Intensive Care (LEICA) (W.t.H., M.W.H., J.H., S.P., P.L.); Department of Nuclear Medicine (K.d.B., H.J.V.), Cardiology (A.O.V., H.L.T.), Anatomy, Embryology and Physiology (A.O.V.), and Neurology (C.V.), Academic Medical Center University of Amsterdam, Amsterdam, The Netherlands; Department of Anesthesiology and Intensive Care Medicine, Trauma Hospital, Graz, Austria (M.R.); Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany (S.P.) and Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts (P.L.).
  • Submitted for publication December 15, 2015. Accepted for publication October 27, 2017.
    Submitted for publication December 15, 2015. Accepted for publication October 27, 2017.×
  • Address correspondence to Dr. Hollmann: Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. m.w.hollmann@amc.uva.nl. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Pain Medicine / Basic Science / Pain Medicine / Pharmacology
Pain Medicine   |   March 2018
Pharmacodynamics and Pharmacokinetics of Lidocaine in a Rodent Model of Diabetic Neuropathy
Anesthesiology 3 2018, Vol.128, 609-619. doi:10.1097/ALN.0000000000002035
Anesthesiology 3 2018, Vol.128, 609-619. doi:10.1097/ALN.0000000000002035
Abstract

Background: Clinical and experimental data show that peripheral nerve blocks last longer in the presence of diabetic neuropathy. This may occur because diabetic nerve fibers are more sensitive to local anesthetics or because the local anesthetic concentration decreases more slowly in the diabetic nerve. The aim of this study was to investigate both hypotheses in a rodent model of neuropathy secondary to type 2 diabetes.

Methods: We performed a series of sciatic nerve block experiments in 25 Zucker Diabetic Fatty rats aged 20 weeks with a neuropathy component confirmed by neurophysiology and control rats. We determined in vivo the minimum local anesthetic dose of lidocaine for sciatic nerve block. To investigate the pharmacokinetic hypothesis, we determined concentrations of radiolabeled (14C) lidocaine up to 90 min after administration. Last, dorsal root ganglia were excised for patch clamp measurements of sodium channel activity.

Results: First, in vivo minimum local anesthetic dose of lidocaine for sciatic nerve motor block was significantly lower in diabetic (0.9%) as compared to control rats (1.4%). Second, at 60 min after nerve block, intraneural lidocaine was higher in the diabetic animals. Third, single cell measurements showed a lower inhibitory concentration of lidocaine for blocking sodium currents in neuropathic as compared to control neurons.

Conclusions: We demonstrate increased sensitivity of the diabetic neuropathic nerve toward local anesthetics, and prolonged residence time of local anesthetics in the diabetic neuropathic nerve. In this rodent model of neuropathy, both pharmacodynamic and pharmacokinetic mechanisms contribute to prolonged nerve block duration.