Burst & High-Frequency Spinal Cord Stimulation Differentially Effect Spinal Neuronal Activity After Radiculopathy

  • Alexander R. Kent
  • Christine L. Weisshaar
  • Lalit Venkatesan
  • Beth A. WinkelsteinEmail author
Original Article


Although burst and high-frequency (HF) spinal cord stimulation (SCS) relieve neuropathic pain, their effects on neuronal hyperexcitability have not been compared. Specifically, it is unknown how the recharge components of burst SCS—either actively balanced or allowed to passively return—and/or different frequencies of HF SCS compare in altering neuronal activity. Neuronal firing rates were measured in the spinal dorsal horn on day 7 after painful cervical nerve root compression in the rat. Motor thresholds (MTs) and evoked neuronal recordings were collected during noxious stimuli before (baseline) and after delivery of SCS using different SCS modes: 10 kHz HF, 1.2 kHz HF, burst with active recharge, or burst with passive recharge. Spontaneous firing rates were also evaluated at baseline and after SCS. The average MT for 10 kHz SCS was significantly higher (p < 0.033) than any other mode. Burst with passive recharge was the only SCS mode to significantly reduce evoked (p = 0.019) and spontaneous (p = 0.0076) firing rates after noxious pinch. This study demonstrates that HF and burst SCS have different MTs and effects on both evoked and spontaneous firing rates, indicating they have different mechanisms of providing pain relief. Since burst with passive recharge was the only waveform to reduce firing, that waveform may be important in the neurophysiological response to stimulation.


SCS Neuropathic pain Electrical stimulation Electrophysiology Spinal cord 



This work was supported by a sponsored research contract from St. Jude Medical/Abbott. We would like to thank Martha Zeeman for her technical support with data analysis. Drs. Kent and Venkatesan were employees of Abbott; although they both contributed to the study design and provided editorial input and review of the manuscript, they were not involved in performing the study or analyzing the data. Dr. Winkelstein has received research funding from St. Jude Medical/Abbott.


  1. 1.
    Campbell, C. M., L. F. Buenaver, S. N. Raja, et al. Dynamic pain phenotypes are associated with spinal cord stimulation-induced reduction in pain: a repeated measures observational Pilot study. Pain Med. 16(7):1349–1360, 2015. Scholar
  2. 2.
    Chang, Y.-W., and B. A. Winkelstein. Schwann cell proliferation and macrophage infiltration are evident at day 14 after painful cervical nerve root compression in the rat. J. Neurotrauma 28(12):2429–2438, 2011. Scholar
  3. 3.
    Compton, A. K., B. Shah, and S. M. Hayek. Spinal cord stimulation: a review. Curr. Pain Headache Rep. 16(1):35–42, 2012. Scholar
  4. 4.
    Courtney, P., A. Espinet, B. Mitchell, et al. Improved pain relief with burst spinal cord stimulation for two weeks in patients using tonic stimulation: results from a small clinical study. Neuromodulation 18(5):361–366, 2015. Scholar
  5. 5.
    Crosby, N. D., M. D. Goodman Keiser, J. R. Smith, M. E. Zeeman, and B. A. Winkelstein. Stimulation parameters define the effectiveness of burst spinal cord stimulation in a rat model of neuropathic pain. Neuromodulation 18:1–8, 2015. Scholar
  6. 6.
    Crosby, N. D., C. L. Weisshaar, J. R. Smith, M. E. Zeeman, M. D. Goodman-Keiser, and B. A. Winkelstein. Burst and tonic spinal cord stimulation differentially activate GABAergic mechanisms to attenuate pain in a rat model of cervical radiculopathy. IEEE Trans. Biomed. Eng. 62(6):1604–1613, 2015. Scholar
  7. 7.
    Crosby, N. D., C. L. Weisshaar, and B. A. Winkelstein. Spinal neuronal plasticity is evident within 1 day after a painful cervical facet joint injury. Neurosci. Lett. 542:102–106, 2013. Scholar
  8. 8.
    Cuellar, J. M., K. Alataris, A. Walker, D. C. Yeomans, and J. F. Antognini. Effect of high-frequency alternating current on spinal afferent nociceptive transmission. Neuromodulation 16(4):318–327, 2013. Scholar
  9. 9.
    De Ridder, D., S. Vanneste, M. Plazier, E. van der Loo, and T. Menovsky. Burst spinal cord stimulation: toward paresthesia-free pain suppression. Neurosurgery 66(5):986–990, 2010. Scholar
  10. 10.
    de Vos, C. C., M. J. Bom, S. Vanneste, M. W. P. M. Lenders, and D. de Ridder. Burst spinal cord stimulation evaluated in patients with failed back surgery syndrome and painful diabetic neuropathy. Neuromodulation 17(2):152–159, 2014. Scholar
  11. 11.
    Deer, T., K. V. Slavin, K. Amirdelfan, et al. Success using neuromodulation with BURST (SUNBURST) study: results from a prospective, randomized controlled trial using a novel burst waveform. Neuromodulation 21(1):56–66, 2018. Scholar
  12. 12.
    Demartini, L., G. Terranova, M. A. Innamorato, et al. Comparison of tonic vs. burst spinal cord stimulation during trial period. Neuromodulation 22(3):327–332, 2019. Scholar
  13. 13.
    Hubbard, R. D., Z. Chen, and B. A. Winkelstein. Transient cervical nerve root compression modulates pain: load thresholds for allodynia and sustained changes in spinal neuropeptide expression. J. Biomech. 41:677–685, 2008. Scholar
  14. 14.
    Hubbard, R. D., and B. A. Winkelstein. Transient cervical nerve root compression in the rat induces bilateral forepaw allodynia and spinal glial activation: mechanical factors in painful neck injuries. Spine 30(17):1924–1932, 2005. Scholar
  15. 15.
    Kapural, L., C. Yu, M. W. Doust, et al. Novel 10-kHz High-frequency therapy (HF10 Therapy) is superior to traditional low-frequency spinal cord stimulation for the treatment of chronic back and leg pain: the SENZA-RCT randomized controlled trial. Anesthesiology 123(4):851–860, 2015. Scholar
  16. 16.
    Kinfe, T. M., S. Muhammad, C. Link, S. Roeske, S. R. Chaudhry, and T. L. Yearwood. Burst spinal cord stimulation increases peripheral antineuroinflammatory interleukin 10 levels in failed back surgery syndrome patients with predominant back pain. Neuromodulation 20(4):322–330, 2017. Scholar
  17. 17.
    Kinfe, T. M., B. Pintea, C. Link, et al. High frequency (10 kHz) or Burst spinal cord stimulation in failed back surgery syndrome patients with predominant back pain: preliminary data from a prospective observational study. Neuromodulation 19(3):268–275, 2016. Scholar
  18. 18.
    Latremoliere, A., and C. J. Woolf. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J. Pain 10(9):895–926, 2009. Scholar
  19. 19.
    Lempka, S. F., C. C. McIntyre, and K. L. Kilgore. Computational analysis of kilohertz frequency spinal cord stimulation for chronic pain management. Anesthesiology 122(6):1362–1376, 2015. Scholar
  20. 20.
    Linderoth, B., and R. D. Foreman. Physiology of spinal cord stimulation: review and update. Neuromodulation 2(3):150–164, 1999. Scholar
  21. 21.
    North, J. M., K.-S. J. Hong, and P. Y. Cho. Clinical outcomes of 1 kHz subperception spinal cord stimulation in implanted patients with failed paresthesia-based stimulation: results of a prospective randomized controlled trial. Neuromodulation 19(7):731–737, 2016. Scholar
  22. 22.
    Quinn, K. P., L. Dong, F. J. Golder, and B. A. Winkelstein. Neuronal hyperexcitability in the dorsal horn after painful facet joint injury. Pain 151(2):414–421, 2010. Scholar
  23. 23.
    Rothman, S. M., K. J. Nicholson, and B. A. Winkelstein. Time-dependent mechanics and measures of glial activation and behavioral sensitivity in a rodent model of radiculopathy. J. Neurotrauma 27(5):803–814, 2010. Scholar
  24. 24.
    Shechter, R., F. Yang, Q. Xu, et al. Conventional and kilohertz-frequency spinal cord stimulation produces intensity- and frequency-dependent inhibition of mechanical hypersensitivity in a rat model of neuropathic pain. Anesthesiology 119(2):422–432, 2013. Scholar
  25. 25.
    Smith, J. R., P. A. Galie, D. R. Slochower, C. L. Weisshaar, P. A. Janmey, and B. A. Winkelstein. Salmon-derived thrombin inhibits development of chronic pain through an endothelial barrier protective mechanism dependent on APC. Biomaterials 80:96–105, 2016. Scholar
  26. 26.
    Song, Z., B. A. Meyerson, and B. Linderoth. High-frequency (1 kHz) spinal cord stimulation—Is pulse shape crucial for the efficacy? A pilot study. Neuromodulation. 18(8):714–720, 2015. Scholar
  27. 27.
    Syré, P. P., C. L. Weisshaar, and B. A. Winkelstein. Sustained neuronal hyperexcitability is evident in the thalamus after a transient cervical radicular injury. Spine. 39(15):E870–E877, 2014. Scholar
  28. 28.
    Tang, R., M. Martinez, M. Goodman-Keiser, J. P. Farber, C. Qin, and R. D. Foreman. Comparison of burst and tonic spinal cord stimulation on spinal neural processing in an animal model. Neuromodulation 17(2):143–151, 2014. Scholar
  29. 29.
    Thomson, S. J., M. Tavakkolizadeh, and S. Love-Jones. Effects of rate on analgesia in kilohertz frequency spinal cord stimulation: results of PROCO randomized controlled trial. Neuromodulation 21(1):67–76, 2018. Scholar
  30. 30.
    Weisshaar, C. L., J. P. Winer, B. B. Guarino, P. A. Janmey, and B. A. Winkelstein. The potential for salmon fibrin and thrombin to mitigate pain subsequent to cervical nerve root injury. Biomaterials 32(36):9738–9746, 2011. Scholar
  31. 31.
    Yakhnitsa, V., B. Linderoth, and B. A. Meyerson. Spinal cord stimulation attenuates dorsal horn neuronal hyperexcitability in a rat model of mononeuropathy. Pain 79(2–3):223–233, 1999.Google Scholar
  32. 32.
    Zimmermann, M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16(2):109–110, 1983. Scholar

Copyright information

© Biomedical Engineering Society 2019

Authors and Affiliations

  1. 1.AbbottSunnyvaleUSA
  2. 2.Department of BioengineeringUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.AbbottPlanoUSA
  4. 4.Department of NeurosurgeryUniversity of PennsylvaniaPhiladelphiaUSA

Personalised recommendations