Skip to main content
SpringerLink
Log in
Book cover

Advanced Procedures for Pain Management pp 93–103Cite as

Neuromodulation: Mechanisms of Action

  • Chapter
  • First Online:

  • 1971 Accesses

Abstract

Neuromodulation may refer to spinal cord stimulation (SCS), peripheral nerve stimulation (PNS), or peripheral nerve field stimulation for the treatment of chronic pain. All neurostimulation treatments share common mechanisms of action that affect the nervous system in order to suppress pain, but each modality seems to have its own unique and particular mechanisms. Multiple clinical and animal studies to date have revealed that neurostimulation therapy involves a complex interaction with multiple structures in the nervous system, with the effect not just attributed to the gate control theory, as initially believed. Improved understanding has led to the development of high-frequency, burst waveform, and dorsal root ganglion (DRG) stimulation.

This is a preview of subscription content, log in via an institution.

References

  1. Kane K, Taub A. A history of local electrical analgesia. Pain. 1975;1:25–138.

    Article  Google Scholar 

  2. Miles J. Electrical stimulation for the relief of pain. Ann R Coll Surg Engl. 1984;66:108–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Shealy CN, Taslitz N, Mortimer JT, Becker DP. Electrical inhibition of pain: experimental evaluation. Anesth Analg. 1967;46:299–305.

    CAS  PubMed  Google Scholar 

  4. Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965;150:971–9.

    Article  CAS  PubMed  Google Scholar 

  5. Arle JE, Carlson KW, Mei L, Iftimia N, Shils JL. Mechanism of dorsal column stimulation to treat neuropathic but not nociceptive pain: analysis with a computational model. Neuromodulation. 2014;17:642–55; discussion 655.

    Article  PubMed  Google Scholar 

  6. Oakley J, Prager J. Spinal cord stimulation—mechanism of action. Spine. 2002;27:2574–83.

    Article  PubMed  Google Scholar 

  7. Roberts MHT, Rees H. Physiological basis of spinal cord stimulation. Pain Rev. 1994;1:184–98.

    Google Scholar 

  8. Handwerker HO, Iggo A, Zimmermann M. Segmental and supraspinal actions on dorsal horn neurons responding to noxious and non-noxious skin stimuli. Pain. 1975;1:147–65.

    Article  CAS  PubMed  Google Scholar 

  9. Meyerson BA, Herregodts P, Linderoth B, Ren B. An experimental animal model of spinal cord stimulation for pain. Stereotact Funct Neurosurg. 1994;62:256–62.

    Article  CAS  PubMed  Google Scholar 

  10. Linderoth B, Meyerson BA. Dorsal column stimulation: modulation of somatosensory and autonomic function. Semin Neurosci. 1995;7:263–77.

    Article  Google Scholar 

  11. Guan Y, Wacnik PW, Yang F, Carteret AF, Chung C-Y, Meyer RA, Raja SN. Spinal cord stimulation-induced analgesia: electrical stimulation of dorsal column and dorsal roots attenuates dorsal horn neuronal excitability in neuropathic rats. Anesthesiology. 2010;113:1392–405.

    Article  PubMed  Google Scholar 

  12. Linderoth B, Foreman RD. Mechanisms of spinal cord stimulation in painful syndromes: role of animal models. Pain Med. 2006;7:S14–26.

    Article  Google Scholar 

  13. Stojanovic MP, Abdi S. Spinal cord stimulation. Pain Physician. 2002;5:156–66.

    PubMed  Google Scholar 

  14. Van Buyten JP, Al-Kaisy A, Smet I, Palmisani S, Smith T. High-frequency spinal cord stimulation for the treatment of chronic back pain patients: results of a prospective multicenter European clinical study. Neuromodulation. 2013;16:59–65; discussion 65–6.

    Article  PubMed  Google Scholar 

  15. Kapural L, Yu C, Doust MW, Gliner BE, Vallejo R, Sitzman BT, 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. 2015;123:851–60.

    Article  PubMed  Google Scholar 

  16. Kapural L, Yu C, Doust MW, Gliner BE, Vallejo R, Sitzman BT, et al. Comparison of 10-kHz high-frequency and traditional low-frequency spinal cord stimulation for the treatment of chronic back and leg pain: 24-month results from a multicenter, randomized, controlled pivotal trial. Neurosurgery. 2016;79(5):667–77.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Miller JP, Eldabe S, Buchser E, Johanek LM, Guan Y, Linderoth B. Parameters of spinal cord stimulation and their role in electrical charge delivery: a review. Neuromodulation. 2016;19:373–84.

    Article  PubMed  Google Scholar 

  18. Lempka SF, McIntyre CC, Kilgore KL, Machado AG. Computational analysis of kilohertz frequency spinal cord stimulation for chronic pain management. Anesthesiology. 2015;122:1362–76.

    Article  CAS  PubMed  Google Scholar 

  19. Shechter R, Yang F, Xu Q, Cheong YK, He SQ, Sdrulla A, 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. 2013;119:422–32.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Song Z, Viisanen H, Meyerson BA, Pertovaara A, Linderoth B. Efficacy of kilohertz-frequency and conventional spinal cord stimulation in rat models of different pain conditions. Neuromodulation. 2014;17:226–34; discussion 234–5.

    Article  PubMed  Google Scholar 

  21. Amir R, Michaelis M, Devor M. Burst discharge in primary sensory neurons: triggered by subthreshold oscillations, maintained by depolarizing after potentials. J Neurosci. 2002;22:1187–98.

    CAS  PubMed  Google Scholar 

  22. Emmers R. Thalamic mechanisms that process a temporal pulse code for pain. Brain Res. 1976;103:425–41.

    Article  CAS  PubMed  Google Scholar 

  23. Radhakrishnan V, Tsoukatos J, Davis KD, Tasker RR, Lozano AM, Dostrovsky JO. A comparison of the burst activity of lateral thalamic neurons in chronic pain and non-pain patients. Pain. 1999;80:567–75.

    Article  CAS  PubMed  Google Scholar 

  24. Lenz FA, Garonzik IM, Zirh TA, Dougherty PM. Neuronal activity in the region of the thalamic principal sensory nucleus (ventralis caudalis) in patients with pain following amputations. Neuroscience. 1998;86:1065–81.

    Article  CAS  PubMed  Google Scholar 

  25. Jahnsen H, Llinás R. Voltage-dependent burst-to-tonic switching of thalamic cell activity: an in vitro study. Arch Ital Biol. 1984;122:73–82.

    CAS  PubMed  Google Scholar 

  26. Swadlow HA, Gusev AG. The impact of ‘bursting’ thalamic impulses at a neocortical synapse. Nat Neurosci. 2001;4:402–8.

    Article  CAS  PubMed  Google Scholar 

  27. Sherman SM. A wake-up call from the thalamus. Nat Neurosci. 2001;4:344–6.

    Article  CAS  PubMed  Google Scholar 

  28. De Ridder D, Vanneste S, Plazier M, van der Loo E, Menovsky T. Burst spinal cord stimulation: toward paresthesia-free pain suppression. Neurosurgery. 2010;66:986–90.

    Article  PubMed  Google Scholar 

  29. De Ridder D, Plazier M, Kamerling N, Menovsky T, Vanneste S. Burst spinal cord stimulation for limb and back pain. World Neurosurg. 2013;80:642–9.

    Article  PubMed  Google Scholar 

  30. Kulkarni B, Bentley DE, Elliott R, Youell P, Watson A, Derbyshire SW, et al. Attention to pain localization and unpleasantness discriminates the functions of the medial and lateral pain systems. Eur J Neurosci. 2005;21:3133–42.

    Article  CAS  PubMed  Google Scholar 

  31. de Vos CC, Bom MJ, Vanneste S, Lenders MW, De Ridder D. Burst spinal cord stimulation evaluated in patients with failed back surgery syndrome and painful diabetic neuropathy. Neuromodulation. 2014;17:152–9.

    Article  PubMed  Google Scholar 

  32. De Ridder D, Vanneste S. Burst and tonic spinal cord stimulation: different and common brain mechanisms. Neuromodulation. 2016;19:47–59.

    Article  PubMed  Google Scholar 

  33. Schu S, Slotty PJ, Bara G, von Knop M, Edgar D, Vesper J. A prospective, randomized, double-blind, placebo-controlled study to examine the effectiveness of burst spinal cord stimulation patterns for the treatment of failed back surgery syndrome. Neuromodulation. 2014;17:443–50.

    Article  PubMed  Google Scholar 

  34. De Ridder D, Vanneste S, Plazier M, Vancamp T. Mimicking the brain: evaluation of St Jude Medical’s Prodigy Chronic Pain System with Burst Technology. Expert Rev Med Devices. 2015;12:143–50.

    Article  PubMed  Google Scholar 

  35. De Ridder D, Lenders MW, De Vos CC, Dijkstra-Scholten C, Wolters R, Vancamp T, et al. A 2-center comparative study on tonic versus burst spinal cord stimulation: amount of responders and amount of pain suppression. Clin J Pain. 2015;31:433–7.

    Article  PubMed  Google Scholar 

  36. Hou S, Kemp K, Grabois M. A systematic evaluation of burst spinal cord stimulation for chronic back and limb pain. Neuromodulation. 2016;19:398–405.

    Article  PubMed  Google Scholar 

  37. Hogan Q. Labat lecture: the primary sensory neuron: where it is, what it does and why it matters. Reg Anesth Pain Med. 2010;35:306–11.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Sapunar D, Kostic S, Banozic A, Puljak L. Dorsal root ganglion—a potential new therapeutic target for neuropathic pain. J Pain Res. 2012;5:31–8.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Van Zundert J, Patijn J, Kessels A, Lame I, van Suijlekom H, van Kleef M. Pulsed radiofrequency adjacent to the cervical dorsal root ganglion in chronic cervical radicular pain: a double blind sham controlled randomized clinical trial. Pain. 2007;127:173–82.

    Article  PubMed  Google Scholar 

  40. McCallum JB, Kwok WM, Sapunar D, Fuchs A, Hogan QH. Painful peripheral nerve injury decreases calcium current in axotomized sensory neurons. Anesthesiology. 2006;105:160–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Rush AM, Dib-Hajj SD, Liu S, Cummins TR, Black JA, Waxman SG. A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons. Proc Natl Acad Sci U S A. 2006;103:8245–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Fields RD. New culprits in chronic pain. Sci Am. 2009;301:50–7.

    Article  CAS  PubMed  Google Scholar 

  43. Gemes G, Koopmeiners A, Rigaud M, Lirk P, Sapunar D, Bangaru ML, et al. Failure of action potential propagation in sensory neurons: mechanisms and loss of afferent filtering in C-type units after painful injury. J Physiol. 2013;591:1111–31.

    Article  CAS  PubMed  Google Scholar 

  44. Krames ES. The dorsal root ganglion in chronic pain and as a target for neuromodulation: a review. Neuromodulation. 2015;18:24–32.

    Article  PubMed  Google Scholar 

  45. St. Jude Medical. A safety and effectiveness trial of spinal cord stimulation of the dorsal root ganglion for chronic lower limb pain (ACCURATE). https://clinicaltrials.gov/ct2/show/NCT01923285

  46. Chung JM, Fang ZR, Hori Y, Lee KH, Willis WD. Prolonged inhibitor of primate spinothalamic tract cells by peripheral nerve stimulation. Pain. 1984;19:259–75.

    Article  CAS  PubMed  Google Scholar 

  47. Ignelzi RJ, Nyquist JK. Excitability changes in peripheral nerve fibers after repetitive electrical stimulation. Implications in pain modulation. J Neurosurg. 1979;51:824–33.

    Article  CAS  PubMed  Google Scholar 

  48. Campbell JN, Taub A. Local analgesia from percutaneous electrical stimulation. A peripheral mechanism. Arch Neurol. 1973;28:347–50.

    Article  CAS  PubMed  Google Scholar 

  49. Abejon D, Deer T, Verrills P. Subcutaneous stimulation: how to assess optimal implantation depth. Neuromodulation. 2011;14:343–8.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, University of South Florida, Tampa, FL, USA

    Nomen Azeem

  2. Tampa Pain Relief Center, Palm Harbor, FL, USA

    Miguel D. Attias

Authors
  1. Nomen Azeem
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Miguel D. Attias
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nomen Azeem .

Editor information

Editors and Affiliations

  1. Lenox Hill Hospital, New York, New York, USA

    Sudhir Diwan

  2. The Center for Pain Relief, Charleston, West Virginia, USA

    Timothy R Deer

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Azeem, N., Attias, M.D. (2018). Neuromodulation: Mechanisms of Action. In: Diwan, S., Deer, T. (eds) Advanced Procedures for Pain Management. Springer, Cham. https://doi.org/10.1007/978-3-319-68841-1_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-68841-1_8

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-68839-8

  • Online ISBN: 978-3-319-68841-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation