title: High-Frequency Stimulation of Dorsal Column Axons: Potential Underlying Mechanism of Paresthesia-Free Neuropathic Pain Relief.
abstract: OBJECTIVE
  Spinal cord stimulation (SCS) treats neuropathic pain through retrograde stimulation of dorsal column axons and their inhibitory effects on wide dynamic range (WDR) neurons. Typical SCS uses frequencies from 50-100 Hz. Newer stimulation paradigms use high-frequency stimulation (HFS) up to 10 kHz and produce pain relief but without paresthesia. Our hypothesis is that HFS preferentially blocks larger diameter axons (12-15 µm) based on dynamics of ion channel gates and the electric potential gradient seen along the axon, resulting in inhibition of WDR cells without paresthesia.
  
  
  METHODS
  We input field potential values from a finite element model of SCS into an active axon model with ion channel subcomponents for fiber diameters 1-20 µm and simulated dynamics on a 0.001 msec time scale.
  
  
  RESULTS
  Assuming some degree of wave rectification seen at the axon, action potential (AP) blockade occurs as hypothesized, preferentially in larger over smaller diameters with blockade in most medium and large diameters occurring between 4.5 and 10 kHz. Simulations show both ion channel gate and virtual anode dynamics are necessary.
  
  
  CONCLUSIONS
  At clinical HFS frequencies and pulse widths, HFS preferentially blocks larger-diameter fibers and concomitantly recruits medium and smaller fibers. These effects are a result of interaction between ion gate dynamics and the "activating function" (AF) deriving from current distribution over the axon. The larger fibers that cause paresthesia in low-frequency simulation are blocked, while medium and smaller fibers are recruited, leading to paresthesia-free neuropathic pain relief by inhibiting WDR cells.
authors.affiliation: Department of Neurosurgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.|Department of Neurosurgery, Harvard Medical School, Boston, MA, USA.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Arle
authors.affiliation: Department of Neurosurgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Longzhi
authors.initials: L
authors.lastname: Mei
authors.affiliation: Department of Neurosurgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Kristen W
authors.identifier: http://orcid.org/0000-0003-2101-3567
authors.initials: KW
authors.lastname: Carlson
authors.affiliation: Department of Anesthesiology, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Jay L
authors.initials: JL
authors.lastname: Shils
mesh_terms: D000200:Action Potentials / Q000502:physiology; D001369:Axons / Q000502:physiology*; D055592:Biophysical Phenomena; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D009437:Neuralgia / Q000209:etiology / Q000628:therapy*; D010147:Pain Measurement; D010292:Paresthesia / Q000150:complications; D013116:Spinal Cord / Q000502:physiology*; D062187:Spinal Cord Stimulation / Q000379:methods*
keywords: 10 kHz; HF10; High-frequency stimulation; chronic pain; mechanisms; nociceptive pain; paresthesia; spinal cord stimulation