Neuromodulation for Spine Pain Care

  • Alexandra R. Adler
  • Mark C. Bicket
  • Shihab U. AhmedEmail author


Electricity has been used as a modality for pain relief since antiquity. Despite early recognition of this analgesic potential, almost two centuries passed before Melzack and Wall published their seminal gate control theory in 1965. The theory, which held that electrical stimulation of the dorsal column of the spinal cord could modulate the transmission of nociceptive signals from the peripheral nervous system, represented a paradigm shift for the treatment of pain. Coupled closely with the first use of an implanted lead that provided electrical stimulation adjacent to the thoracic dorsal column and relieved pain in the chest wall of a cancer patient, these two events ushered in a new era of pain relief from the targeted application of electrical devices. Incremental progress in the field has led to various improvements in hardware design and implantation techniques, which set the stage for spinal cord stimulation (SCS) to serve as an evidence-based treatment for a variety of chronic pain conditions.

Initially, the main indications for SCS were difficult-to-treat pain conditions such as back and leg pain persisting after spine surgery, formerly referred to as failed back surgery syndrome (FBSS) and complex regional pain syndrome (CRPS). Studies have demonstrated superior outcomes with SCS versus reoperation in patients with persistent leg pain with FBSS. More recently, with the advent of newer SCS technologies, the list of indications with evidence favoring SCS has grown to include axial lower back pain, which did not respond well to the earlier SCS technology.

This chapter will review the mechanisms of action of SCS, the modes of SCS, indications specific to different types of spinal pain, efficacy data, and the implantation process. While clinical trials support the use of SCS for analgesia, the basic science foundation for neurostimulation remains incomplete and an area of active inquiry. Research continues to investigate the ability of SCS to modulate pain through understanding its molecular mechanisms, the role of pain pathways including descending inhibition, and the involvement of spinal cord dorsal horn stimulation to alter pain processing in the cortex. Indeed, clinical and preclinical studies using functional MRI (fMRI) have confirmed that SCS acts at both the spinal and supraspinal level and hint at future breakthroughs that may advance the ability to relieve pain and suffering in the years to come.


Spinal cord stimulation Chronic pain Limb pain Back pain Burst stimulation High-frequency stimulation Dorsal root ganglion stimulation 


  1. 1.
    Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965;150(3699):971–9.PubMedGoogle Scholar
  2. 2.
    Wesley J. The desideratum: or, electricity made plain and useful. In: By a lover of mankind, and of common sense [i.e. John Wesley]. 4th ed. London: Bailliere, Tindall and Cox; 1778.Google Scholar
  3. 3.
    Moore DM, McCrory C. Spinal cord stimulation. BJA Education. 2016;16(8):258–63.Google Scholar
  4. 4.
    Shealy CN, Mortimer JT, Reswick JB. Electrical inhibition of pain by stimulation of the dorsal columns: preliminary clinical report. Anesth Analg. 1967;46(4):489–91.PubMedGoogle Scholar
  5. 5.
    Shealy CN, Mortimer JT, Hagfors NR. Dorsal column electroanalgesia. J Neurosurg. 1970;32(5):560–4.PubMedGoogle Scholar
  6. 6.
    Krames E, Peckham PH. Rezai AR. Neuromodulation: Academic Press; 2018. 1 p.Google Scholar
  7. 7.
  8. 8.
    Zhang TC, Janik JJ, Grill WM. Mechanisms and models of spinal cord stimulation for the treatment of neuropathic pain. Brain Res. 2014;1569:19–31.PubMedGoogle Scholar
  9. 9.
    Buonocore M, Bonezzi C, Barolat G. Neurophysiological evidence of antidromic activation of large myelinated fibres in lower limbs during spinal cord stimulation. Spine. 2008;33(4):E90–3.PubMedGoogle Scholar
  10. 10.
    Linderoth B, Foreman RD. Conventional and novel spinal stimulation algorithms: hypothetical mechanisms of action and comments on outcomes. Neuromodulation. 2017;20(6):525–33.PubMedGoogle Scholar
  11. 11.
    Cui JG, O’Connor WT, Ungerstedt U, Linderoth B, Meyerson BA. Spinal cord stimulation attenuates augmented dorsal horn release of excitatory amino acids in mononeuropathy via a GABAergic mechanism. Pain. 1997;73(1):87–95.PubMedGoogle Scholar
  12. 12.
    Meyerson BA, Linderoth B. Mechanisms of spinal cord stimulation in neuropathic and vasculopathic pain: present status of knowledge – and views for the future. Philadelphia: Elsevier; 2003. p. 161–82.Google Scholar
  13. 13.
    Guan Y, Raja SN. Wide-dynamic-range neurons are heterogeneous in windup responsiveness to changes in stimulus intensity and isoflurane anesthesia level in mice. J Neurosci Res. 2010;88(10):2272–83.PubMedGoogle Scholar
  14. 14.
    Cui JG, Linderoth B, Meyerson BA. Effects of spinal cord stimulation on touch-evoked allodynia involve GABAergic mechanisms. An experimental study in the mononeuropathic rat. Pain. 1996;66(2–3):287–95.PubMedGoogle Scholar
  15. 15.
    Cui JG, Meyerson BA, Sollevi A, Linderoth B. Effect of spinal cord stimulation on tactile hypersensitivity in mononeuropathic rats is potentiated by simultaneous GABA(B) and adenosine receptor activation. Neurosci Lett. 1998;247(2–3):183–6.PubMedGoogle Scholar
  16. 16.
    Schechtmann G, Song Z, Ultenius C, Meyerson BA, Linderoth B. Cholinergic mechanisms involved in the pain relieving effect of spinal cord stimulation in a model of neuropathy. Pain. 2008;139(1):136–45.PubMedGoogle Scholar
  17. 17.
    Linderoth B, Foreman RD. Physiology of spinal cord stimulation: review and update. Neuromodulation. 2nd ed. 1999;2(3):150–64.PubMedGoogle Scholar
  18. 18.
    Linderoth B, Meyerson BA. Spinal cord stimulation: exploration of the physiological basis of a widely used therapy. Anesthesiology. 2010;113(6):1265–7.PubMedGoogle Scholar
  19. 19.
    Sato KL, King EW, Johanek LM, Sluka KA. Spinal cord stimulation reduces hypersensitivity through activation of opioid receptors in a frequency-dependent manner. Eur J Pain. 2013;17(4):551–61.PubMedGoogle Scholar
  20. 20.
    Kriek N, Schreurs MWJ, Groeneweg JG, Dik WA, Tjiang GCH, Gültuna I, et al. Spinal cord stimulation in patients with complex regional pain syndrome: a possible target for immunomodulation? Neuromodulation: Technol Neural Interface. 2017;21(1):77–86.Google Scholar
  21. 21.
    Kiriakopoulos ET, Tasker RR, Nicosia S, Wood ML, Mikulis DJ. Functional magnetic resonance imaging: a potential tool for the evaluation of spinal cord stimulation: technical case report. Neurosurgery. 1997;41(2):501–4.PubMedGoogle Scholar
  22. 22.
    Rasche D, Siebert S, Stippich C, Kress B, Nennig E, Sartor K, et al. Spinal cord stimulation in Failed-Back-Surgery-Syndrome. Preliminary study for the evaluation of therapy by functional magnetic resonance imaging (fMRI). Schmerz. 2005;19(6):497–500–502–5.Google Scholar
  23. 23.
    Deogaonkar M, Sharma M, Oluigbo C, Nielson DM, Yang X, Vera-Portocarrero L, et al. Spinal cord stimulation (SCS) and functional magnetic resonance imaging (fMRI): modulation of cortical connectivity with therapeutic SCS. Neuromodulation. 2016;19(2):142–53.PubMedGoogle Scholar
  24. 24.
    El-Khoury C, Hawwa N, Baliki M, Atweh SF, Jabbur SJ, Saadé NE. Attenuation of neuropathic pain by segmental and supraspinal activation of the dorsal column system in awake rats. Neuroscience. 2002;112(3):541–53.PubMedGoogle Scholar
  25. 25.
    Saadé NE, Tabet MS, Atweh SF, Jabbur SJ. Modulation of segmental mechanisms by activation of a dorsal column brainstem spinal loop. Brain Res. 1984;310(1):180–4.PubMedGoogle Scholar
  26. 26.
    Naoum JJ, Arbid EJ. Spinal cord stimulation for chronic limb ischemia. Methodist Debakey Cardiovasc J. 2013 Apr;9(2):99–102.PubMedPubMedCentralGoogle Scholar
  27. 27.
    De Caridi G, Massara M, David A, Giardina M, La Spada M, Stilo F, et al. Spinal cord stimulation to achieve wound healing in a primary lower limb critical ischaemia referral centre. Int Wound J. 2014;13(2):220–5.PubMedGoogle Scholar
  28. 28.
    Lanza GA, Grimaldi R, Greco S, Ghio S, Sarullo F, Zuin G, et al. Spinal cord stimulation for the treatment of refractory angina pectoris: a multicenter randomized single-blind study (the SCS-ITA trial). Pain. International Association for the Study of Pain;. 2011;152(1):45–52.PubMedGoogle Scholar
  29. 29.
    Courtney P, Espinet A, Mitchell B, Russo M, Muir A, Verrills P, 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. 2015;18(5):361–6.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Kreis PG, Fishman S. Spinal cord stimulation. New York: Oxford University Press; 2009.Google Scholar
  31. 31.
    Veizi E, Hayek SM, North J, Brent Chafin T, Yearwood TL, Raso L, et al. Spinal Cord Stimulation (SCS) with anatomically guided (3D) neural targeting shows superior chronic axial low back pain relief compared to traditional SCS—LUMINA Study. Pain Med. 2017;18(8):1534–48.Google Scholar
  32. 32.
    Liem L, Russo M, Huygen FJPM, Van Buyten J-P, Smet I, Verrills P, et al. One-year outcomes of spinal cord stimulation of the dorsal root ganglion in the treatment of chronic neuropathic pain. Neuromodulation. 2015;18(1):41–8; discussion 48–9.PubMedGoogle Scholar
  33. 33.
    Verrills P, Sinclair C, Barnard A. A review of spinal cord stimulation systems for chronic pain. J Pain Res. 2016;9:481–92.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Russo M, Van Buyten J-P. 10-kHz high-frequency SCS therapy: a clinical summary. Pain Med. 2015;16(5):934–42.PubMedGoogle Scholar
  35. 35.
    Deer TR, Mekhail N, Provenzano D, Pope J, Krames E, Thomson S, et al. The appropriate use of neurostimulation: avoidance and treatment of complications of neurostimulation therapies for the treatment of chronic pain. Neuromodulation: Technol Neural Interface. 2nd ed. 2014;17(6):571–98.Google Scholar
  36. 36.
    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(4):851–60.PubMedGoogle Scholar
  37. 37.
    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: Technol Neural Interface. 6 ed. 2014;17(3):226–35.Google Scholar
  38. 38.
    De Ridder D, Plazier M, Kamerling N, Menovsky T, Vanneste S. Burst spinal cord stimulation for limb and back pain. WNEU. Elsevier Inc;. 2013;80(5):642–649.e1.Google Scholar
  39. 39.
    Gong W-Y, Johanek LM, Sluka KA. A comparison of the effects of burst and tonic spinal cord stimulation on hyperalgesia and physical activity in an animal model of neuropathic pain. Anesth Analg. 2016;122(4):1178–85.PubMedGoogle Scholar
  40. 40.
    North RB, Kidd DH, Farrokhi F, Piantadosi SA. Spinal cord stimulation versus repeated lumbosacral spine surgery for chronic pain: a randomized, controlled trial. Neurosurgery. 2005;56(1):98–107.PubMedGoogle Scholar
  41. 41.
    Grider JS, Manchikanti L, Carayannopoulos A, Sharma ML, Balog CC, Harned ME, et al. Effectiveness of spinal cord stimulation in chronic spinal pain: a systematic review. Pain Physician. 2016;19(1):E33–54.PubMedGoogle Scholar
  42. 42.
    Taylor RS, Desai MJ, Rigoard P, Taylor RJ. Predictors of pain relief following spinal cord stimulation in chronic back and leg pain and failed back surgery syndrome: a systematic review and meta-regression analysis. Pain Pract. 2014;14(6):489–505.PubMedGoogle Scholar
  43. 43.
    Song JJ, Popescu A, Bell RL. Present and potential use of spinal cord stimulation to control chronic pain. Pain Physician. 2014;17(3):235–46.PubMedGoogle Scholar
  44. 44.
    Kumar K, Taylor RS, Jacques L, Eldabe S, Meglio M, Molet J, et al. Spinal cord stimulation versus conventional medical management for neuropathic pain: a multicentre randomised controlled trial in patients with failed back surgery syndrome. Pain. 2007;132(1):179–88.PubMedGoogle Scholar
  45. 45.
    Kumar K, Taylor RS, Jacques L, Eldabe S, Meglio M, Molet J, et al. The effects of spinal cord stimulation in neuropathic pain are sustained: a 24-month follow-up of the prospective randomized controlled multicenter trial of the effectiveness of spinal cord stimulation. Neurosurgery. 2008;63(4):762–70.. –discussion 770.PubMedGoogle Scholar
  46. 46.
    Deer T, Slavin KV, Amirdelfan K, North RB, Burton AW, Yearwood TL, et al. Success using neuromodulation with BURST (SUNBURST) study: results from a prospective, randomized controlled trial using a novel burst waveform. Neuromodulation. 2018;21(1):56–66.PubMedGoogle Scholar
  47. 47.
    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. Neurosurgery. 2016;79(5):667–77.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Van Buyten J-P, 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: Technol Neural Interface. 2012;16(1):59–66.Google Scholar
  49. 49.
    Al-Kaisy A, Palmisani S, Smith TE, Carganillo R, Houghton R, Pang D, Burgoyne W, et al. Long-term improvements in chronic axial low back pain patients without previous spinal surgery: a cohort analysis of 10-kHz high-frequency spinal cord stimulation over 36 months. Pain Med. 2017;44(2):119–8.Google Scholar
  50. 50.
    Al-Kaisy A, Van Buyten J-P, Smet I, Palmisani S, Pang D, Smith T. Sustained effectiveness of 10 kHz high-frequency spinal cord stimulation for patients with chronic, low back pain: 24-month results of a prospective multicenter study. Pain Med. 2014;15(3):347–54.PubMedGoogle Scholar
  51. 51.
    Al-Kaisy A, Palmisani S, Smith TE, Pang D, Lam K, Burgoyne W, et al. 10 kHz high-frequency spinal cord stimulation for chronic axial low back pain in patients with no history of spinal surgery: a preliminary, prospective, open label and proof-of-concept study. Neuromodulation. 2017;20(1):63–70.PubMedGoogle Scholar
  52. 52.
    Perruchoud C, Eldabe S, Batterham AM, Madzinga G, Brookes M, Durrer A, et al. Analgesic efficacy of high-frequency spinal cord stimulation: a randomized double-blind placebo-controlled study. Neuromodulation: Technol Neural Interface. 2013;16(4):363–9.Google Scholar
  53. 53.
    De Andres J, Monsalve-Dolz V, Fabregat-Cid G, Villanueva-Perez V, Harutyunyan A, Asensio-Samper JM, et al. Prospective, randomized blind effect-on-outcome study of conventional vs high-frequency spinal cord stimulation in patients with pain and disability due to failed back surgery syndrome. Pain Med. 2017;18(12):2401–21.PubMedGoogle Scholar
  54. 54.
    Nizard J, Raoul S, Nguyen J-P, Lefaucheur J-P. Invasive stimulation therapies for the treatment of refractory pain. Discov Med. 2012;14(77):237–46.PubMedGoogle Scholar
  55. 55.
    Goebel A. Complex regional pain syndrome in adults. Rheumatology (Oxford). 2011;50(10):1739–50.Google Scholar
  56. 56.
    Kemler MA, Barendse GA, van Kleef M, de Vet HC, Rijks CP, Furnée CA, et al. Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy. N Engl J Med. 2000;343(9):618–24.PubMedGoogle Scholar
  57. 57.
    Kemler MA, De Vet HCW, Barendse GAM, Van Den Wildenberg FAJM, Van Kleef M. The effect of spinal cord stimulation in patients with chronic reflex sympathetic dystrophy: two years’ follow-up of the randomized controlled trial. Ann Neurol. 2004;55(1):13–8.PubMedGoogle Scholar
  58. 58.
    Tronnier V, Birklein F. Spinal cord stimulation, from diagnosis-oriented to mechanism-based treatment. Eur J Pain. European Federation of International Association for the Study of Pain Chapters;. 2010;14(2):111–2.PubMedGoogle Scholar
  59. 59.
    Deer TR, Levy RM, Kramer J, Poree L, Amirdelfan K, Grigsby E, et al. Dorsal root ganglion stimulation yielded higher treatment success rate for complex regional pain syndrome and causalgia at 3 and 12 months. Pain. 2017;158(4):669–81.PubMedGoogle Scholar
  60. 60.
    Crapanzano JT, Harrison-Bernard LM, Jones MR, Kaye AD, Richter EO, Potash MN. High frequency spinal cord stimulation for complex regional pain syndrome: a case report. Pain Physician. 2017;20(1):E177–82.PubMedGoogle Scholar
  61. 61.
    Levine AB, Parrent AG, MacDougall KW. Stimulation of the spinal cord and dorsal nerve roots for chronic groin, pelvic, and abdominal pain. Pain Physician. 2016;19(6):405–12.PubMedGoogle Scholar
  62. 62.
    Lepski G, Vahedi P, Tatagiba MS, Morgalla M. Combined spinal cord and peripheral nerve field stimulation for persistent post-herniorrhaphy pain. Neuromodulation. 2013;16(1):84–8; discussion 88–9.PubMedGoogle Scholar
  63. 63.
    Abd-Elsayed A, Lee S, King C. Retrograde placement of spinal cord stimulator leads for treating resistant pelvic pain. Saudi J Anaesth. 2017;11(3):366–7.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Abd-Elsayed A, Schiavoni N, Sachdeva H. Efficacy of spinal cord stimulators in treating peripheral neuropathy: a case series. J Clin Anesth. 2016;28:74–7.PubMedGoogle Scholar
  65. 65.
    Blackburn DR, Romers CC, Copeland LA, Lynch W, Nguyen DD, Zeber JE, et al. Presurgical psychological assessments as correlates of effectiveness of spinal cord stimulation for chronic pain reduction. Neuromodulation: Technol Neural Interface. 4 ed. 2016;19(4):422–8.Google Scholar
  66. 66.
    Beltrutti D, Lamberto A, Barolat G, Bruehl SP, Doleys D, Krames E, et al. The psychological assessment of candidates for spinal cord stimulation for chronic pain management. Pain Pract. 2004;4(3):204–21.PubMedGoogle Scholar
  67. 67.
    Narouze S, Benzon HT, Provenzano D, Buvanendran A, De Andres J, Deer T, et al. Interventional spine and pain procedures in patients on antiplatelet and anticoagulant medications (second edition). Reg Anesth Pain Med. 2017;42:1–38.Google Scholar
  68. 68.
    Campbell CM, Jamison RN, Edwards RR. Psychological screening/phenotyping as predictors for spinal cord stimulation. Curr Pain Headache Rep. 2013;17(1):307.PubMedPubMedCentralGoogle Scholar
  69. 69.
    Stojanovic MP, Higgins DM, Popescu A, Bogduk N. COMBI: a convenient tool for clinical outcome assessment in conventional practice. Pain Med. 2015;16(3):513–9.PubMedGoogle Scholar
  70. 70.
    Stojanovic MP, Abdi S. Spinal cord stimulation. Pain Physician. 2002;5(2):156–66.PubMedGoogle Scholar
  71. 71.
    Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013;70:195–283.PubMedGoogle Scholar
  72. 72.
    Bendersky D, Yampolsky C. Is spinal cord stimulation safe? A review of its complications. WNEU. 2014;82(6):1359–68.Google Scholar
  73. 73.
    Mekhail NA, Mathews M, Nageeb F, Guirguis M, Mekhail MN, Cheng J. Retrospective review of 707 cases of spinal cord stimulation: indications and complications. Pain Pract. 2011;11(2):148–53.PubMedGoogle Scholar
  74. 74.
    Eldabe S, Buchser E, Duarte RV. Complications of spinal cord stimulation and peripheral nerve stimulation techniques: a review of the literature. Pain Med. 2015;46:pnv025–12.Google Scholar
  75. 75.
    Babu R, Hazzard MA, Huang KT, Ugiliweneza B, Patil CG, Boakye M, Lad SP. Outcomes of percutaneous and paddle lead implantation for spinal cord stimulation: a comparative analysis of complications, reoperation rates, and health-care costs. Neuromodulation: Technol Neural Interface. 2013;16(5):418–27.Google Scholar
  76. 76.
    Henderson JM, Schade CM, Sasaki J, Caraway DL, Oakley JC. Prevention of mechanical failures in implanted spinal cord stimulation systems. Neuromodulation. 2006;9(3):183–91.PubMedGoogle Scholar
  77. 77.
    Buvanendran A, Young AC. Spinal epidural hematoma after spinal cord stimulator trial lead placement in a patient taking aspirin. Reg Anesth Pain Med. 2014;39(1):70–2.PubMedGoogle Scholar
  78. 78.
    Cameron T. Safety and efficacy of spinal cord stimulation for the treatment of chronic pain: a 20-year literature review. J Neurosurg. 2004;100(3 Suppl Spine):254–67.PubMedGoogle Scholar
  79. 79.
    Provenzano DA, Deer T, Luginbuhl Phelps A, Drennen ZC, Thomson S, Hayek SM, et al. An international survey to understand infection control practices for spinal cord stimulation. Neuromodulation. 2016;19(1):71–84.PubMedGoogle Scholar
  80. 80.
    Hoelzer BC, Bendel MA, Deer TR, Eldrige JS, Walega DR, Wang Z, et al. Spinal cord stimulator implant infection rates and risk factors: a multicenter retrospective study. Neuromodulation: Technol Neural Interface. 2017;20(6):558–62.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Alexandra R. Adler
    • 1
  • Mark C. Bicket
    • 2
  • Shihab U. Ahmed
    • 3
    Email author
  1. 1.Department of Anesthesia, Critical Care and Pain MedicineMassachusetts General HospitalBostonUSA
  2. 2.Department of Anesthesiology and Critical Care MedicineJohns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Department of Anesthesia, Critical Care and Pain MedicineMassachusetts General Hospital, Harvard Medical SchoolBostonUSA

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