title: Combined KHFAC + DC nerve block without onset or reduced nerve conductivity after block.
abstract: OBJECTIVE
  Kilohertz frequency alternating current (KHFAC) waveforms have been shown to provide peripheral nerve conductivity block in many acute and chronic animal models. KHFAC nerve block could be used to address multiple disorders caused by neural over-activity, including blocking pain and spasticity. However, one drawback of KHFAC block is a transient activation of nerve fibers during the initiation of the nerve block, called the onset response. The objective of this study is to evaluate the feasibility of using charge balanced direct current (CBDC) waveforms to temporarily block motor nerve conductivity distally to the KHFAC electrodes to mitigate the block onset-response.
  
  
  METHODS
  A total of eight animals were used in this study. A set of four animals were used to assess feasibility and reproducibility of a combined KHFAC + CBDC block. A following randomized study, conducted on a second set of four animals, compared the onset response resulting from KHFAC alone and combined KHFAC + CBDC waveforms. To quantify the onset, peak forces and the force-time integral were measured during KHFAC block initiation. Nerve conductivity was monitored throughout the study by comparing muscle twitch forces evoked by supra-maximal stimulation proximal and distal to the block electrodes. Each animal of the randomized study received at least 300 s (range: 318-1563 s) of cumulative dc to investigate the impact of combined KHFAC + CBDC on nerve viability.
  
  
  RESULTS
  The peak onset force was reduced significantly from 20.73 N (range: 18.6-26.5 N) with KHFAC alone to 0.45 N (range: 0.2-0.7 N) with the combined CBDC and KHFAC block waveform (p < 0.001). The area under the force curve was reduced from 6.8 Ns (range: 3.5-21.9 Ns) to 0.54 Ns (range: 0.18-0.86 Ns) (p < 0.01). No change in nerve conductivity was observed after application of the combined KHFAC + CBDC block relative to KHFAC waveforms.
  
  
  CONCLUSIONS
  The distal application of CBDC can significantly reduce or even completely prevent the KHFAC onset response without a change in nerve conductivity.
authors.affiliation: Case Western Reserve University, Cleveland, OH, USA. Oculeve, Inc., South San Francisco, CA, USA.
authors.forename: Manfred
authors.initials: M
authors.lastname: Franke
authors.forename: Tina
authors.initials: T
authors.lastname: Vrabec
authors.forename: Jesse
authors.initials: J
authors.lastname: Wainright
authors.forename: Niloy
authors.initials: N
authors.lastname: Bhadra
authors.forename: Narendra
authors.initials: N
authors.lastname: Bhadra
authors.forename: Kevin
authors.initials: K
authors.lastname: Kilgore
mesh_terms: D000818:Animals; D004558:Electric Stimulation / Q000379:methods*; D005240:Feasibility Studies; D009119:Muscle Contraction / Q000502:physiology*; D053580:Muscle Strength / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation* / Q000502:physiology*; D009407:Nerve Block / Q000379:methods*; D009431:Neural Conduction / Q000502:physiology*; D010525:Peripheral Nerves / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley