Pharmacodynamics and pharmacokinetics of lidocaine in a rodent model of diabetic neuropathy
| Autor: | Hein J. Verberne, Susanne Picardi, Markus W. Hollmann, Hanno L. Tan, Werner ten Hoope, Kora de Bruin, Janneke Horn, Camiel Verhamme, Arie O. Verkerk, Marcel Rigaud, Philipp Lirk |
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| Přispěvatelé: | Graduate School, Anesthesiology, Amsterdam Neuroscience - Neuroinfection & -inflammation, AII - Inflammatory diseases, ACS - Heart failure & arrhythmias, Nuclear Medicine, Radiology and Nuclear Medicine, Amsterdam Cardiovascular Sciences, Medical Biology, Cardiology, AII - Infectious diseases, Neurology, Intensive Care Medicine, APH - Quality of Care, ACS - Diabetes & metabolism, ACS - Microcirculation |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
Diabetic neuropathy Lidocaine medicine.drug_class medicine.medical_treatment 03 medical and health sciences 0302 clinical medicine Diabetic Neuropathies 030202 anesthesiology Diabetes mellitus Medicine Animals Anesthetics Local Sodium channel activity business.industry Local anesthetic Nerve Block medicine.disease Sciatic Nerve Rats Disease Models Animal Anesthesiology and Pain Medicine Pharmacodynamics Anesthesia Nerve block Sciatic nerve business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Anesthesiology, 128(3), 609-619. Lippincott Williams and Wilkins |
| ISSN: | 0003-3022 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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