title: Effect of local and intravenous lidocaine on ongoing activity in injured afferent nerve fibers.
abstract: Lidocaine applied systemically or locally attenuates neuropathic pain in patients. Here we tested the hypothesis that ectopic activity in injured afferent A- or C-fibers is suppressed by lidocaine. In rats the sural nerve (skin nerve) or lateral gastrocnemius-soleus nerve (muscle nerve) was crushed. Four to 11 days after crush lesion afferent fibers were isolated from the lesioned nerves in bundles rostral to the injury site. Ongoing ectopic activity was recorded from 75 A-fibers (muscle N=43, skin N=32) and 69 C-fibers (muscle N=30, skin N=39). Most afferent fibers were functionally characterized by their responses to mechanical and thermal (mostly heat) stimuli applied at or distal to the nerve injury site. Low-threshold cold-sensitive cutaneous C-fibers were excluded from the analysis. Lidocaine was either applied to the nerve at or distal to the injury site in concentrations of 1 to 1000 μg/mL or injected i.v. in doses of 0.09 to 9 mg/kg (skin) or 0.047 to 4.7 mg/kg (muscle). Local application of lidocaine depressed ectopic activity in A- and C-fibers dose-dependently. Depression was weaker in C- than in A-fibers. Intravenous application of lidocaine depressed ongoing ectopic activity in A- and C-fibers dose-dependently. Responses to heat or mechanical stimulation of the injured nerve were not suppressed at the highest concentrations of lidocaine. The results support the hypothesis that decrease of neuropathic pain following local or systemic application of a local anesthetic is related to decrease of ectopic ongoing activity in injured afferent nerve fibers.
authors.affiliation: Physiologisches Institut, Christian-Albrechts-Universität zu Kiel, Kiel, Germany Division of Neurological Pain Research and Therapy, Department of Neurology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Kirillova
authors.forename: Alina
authors.initials: A
authors.lastname: Teliban
authors.forename: Natalia
authors.initials: N
authors.lastname: Gorodetskaya
authors.forename: Lydia
authors.initials: L
authors.lastname: Grossmann
authors.forename: Fabian
authors.initials: F
authors.lastname: Bartsch
authors.forename: Vanessa H
authors.initials: VH
authors.lastname: Rausch
authors.forename: Marek
authors.initials: M
authors.lastname: Struck
authors.forename: Jan
authors.initials: J
authors.lastname: Tode
authors.forename: Ralf
authors.initials: R
authors.lastname: Baron
authors.forename: Wilfrid
authors.initials: W
authors.lastname: Jänig
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D004558:Electric Stimulation; D008012:Lidocaine / Q000008:administration & dosage*; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects*; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012867:Skin / Q000294:innervation; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D008012:Lidocaine