title: Mexiletine and lidocaine suppress the excitability of dorsal horn neurons.
abstract: BACKGROUND
  Spinal sensitization and facilitatory processes in dorsal horn neurons after nerve injury alter spinal outflow leading to enhanced pain perception and chronic pain syndromes. Clinically used Na+ channel blockers at doses which do not block conduction can relieve such chronic pain. Although much attention has been paid to their effect upon afferents, less work has been done with their effect on the excitability of central sensory neurons. Thus, we investigated the effects of the Na+ channel blockers mexiletine and lidocaine on sensory spinal dorsal horn neurons.
  
  
  METHODS
  Patch-clamp recordings were directly performed in visualized neurons of the substantia gelatinosa in the spinal cord of young rats to investigate the effect of mexiletine and lidocaine in different types of dorsal horn neurons (tonically firing, adapting-firing, and single spike neurons).
  
  
  RESULTS
  All three different types of neurons responded dose-dependently to mexiletine and lidocaine. Both local anesthetics reversibly inhibited Na+ and K+ currents. The half-maximal inhibitory concentration for Na+ conductance block was 89 +/- 2 or 54 +/- 6 microM and for delayed-rectifier K+ conductance block was 582 +/- 36 or 398 +/- 14 microM for lidocaine and mexiletine, respectively. The inhibition of Na+ and K+ currents consecutively altered the properties of single action potentials and reduced the firing rate of tonically firing and adapting-firing neurons.
  
  
  CONCLUSIONS
  In clinically relevant concentrations, lidocaine and mexiletine reduced the excitability of sensory dorsal horn neurons via a blockade of Na+ and K+ channels. Our work confirms that, in addition to the peripheral effects of lidocaine and mexiletine, modulation of voltage-gated ion channels in the central nervous system contributes to the antinociceptive effects of these drugs used in pain therapy.
authors.affiliation: Department of Anesthesiology, Intensive Care Medicine, Pain Therapy, University Clinic Giessen and Marburg GmbH, Giessen, Germany. andrea.olschewski@medunigraz.at
authors.forename: Andrea
authors.initials: A
authors.lastname: Olschewski
authors.forename: Rose
authors.initials: R
authors.lastname: Schnoebel-Ehehalt
authors.forename: Yingji
authors.initials: Y
authors.lastname: Li
authors.forename: Bi
authors.initials: B
authors.lastname: Tang
authors.forename: Michael E
authors.initials: ME
authors.lastname: Bräu
authors.forename: Matthias
authors.initials: M
authors.lastname: Wolff
mesh_terms: D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D008801:Mexiletine / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats
chemical_list: D008801:Mexiletine; D008012:Lidocaine