Clinical Applications of Neuromodulation: Section on Angina and Peripheral Vascular Disease



Clinical neuromodulation refers to the use of electrical stimulation of a peripheral nerve, the spinal cord, or the brain for relief of pain. For centuries, physicians have been interested in deriving therapeutic benefit from the use of electrical impulses to treat a variety of diseases. In fact, the first medical use of electricity is credited to a Roman physician named Scribonius Largus who described the use of the electric torpedo fish in the treatment of headaches and gouty arthritis. In his work titled Compositiones Medicae [1], Scribonius described the placement of a fish across the forehead or affected area to deliver a shock that alleviated pain much like a modern transcutaneous electrical nerve stimulators (TENS). As human understanding and utilization of electricity evolved, so did its use in the treatment of various disease states.


Neuropathic Pain Spinal Cord Stimulation Transcutaneous Electrical Nerve Stimulator Peripheral Arterial Occlusive Disease Nociceptive Pain 
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  1. 1.
    Largus S. Compositiones. In: Helmreick G, editor. Leipzig: Teubner; 1887.Google Scholar
  2. 2.
    Head H, Thompson T. The grouping of afferent impulses within the spinal cord. Brain. 1906;29:537–741.CrossRefGoogle Scholar
  3. 3.
    Head H, Holmes G. Sensory disturbances from cerebral lesions. Brain. 1911;34:103–254.CrossRefGoogle Scholar
  4. 4.
    Mazars G, Roge R, et al. Results of the stimulation of the spinothalamic fasciculus and their bearing on the physiopathology of pain. Rev Prat. 1960;103:136–8.PubMedGoogle Scholar
  5. 5.
    Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965;150(699):971–9.CrossRefPubMedGoogle Scholar
  6. 6.
    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.CrossRefPubMedGoogle Scholar
  7. 7.
    Lindblom U, Meyerson BA. Influence on touch, vibration and cutaneous pain of dorsal column stimulation in man. Pain. 1975;1:257–70.CrossRefPubMedGoogle Scholar
  8. 8.
    Linderoth B, Meyerson BA. Dorsal column stimulation: modulation of somatosensory and autonomic function. In: Mcmahon SB, Wall PD, editors. The neurobiology of pain, Seminars in the neurosciences. London: Academic; 1995. p. 263–77.Google Scholar
  9. 9.
    Campbell JN, Davis KD, Meyer RA, et al. The mechanism by which spinal cord stimulation affects pain: evidence for a new hypothesis. Pain. 1990;5:S223.Google Scholar
  10. 10.
    Dickenson AH. Gate control theory of pain stands the test of time. Br J Anaesth. 2002;88(6):755–7.CrossRefPubMedGoogle Scholar
  11. 11.
    Simpson B. Electrical stimulation and the relief of pain. Pain Res Clin Manag. 2003;15:131–42.Google Scholar
  12. 12.
    Eddicks S, Maier-Hauff K, Schenk M, Müller A, Baumann G, Theres H. Thoracic spinal cord stimulation improves functional status and relieves symptoms in patients with refractory angina pectoris: the first placebo-controlled randomised study. Heart. 2007;93:585–90.CrossRefPubMedGoogle Scholar
  13. 13.
    Hautvast RW, DeJongste MJ, Staal MJ, van Gilst WH, Lie KL. Spinal cord stimulation in chronic intractable angina pectoris: a randomized, controlled efficacy study. Am Heart J. 1988;136:1114–20.CrossRefGoogle Scholar
  14. 14.
    Myerson B, Linderoth B. Spinal cord stimulation: mechanisms of action in neuropathic and ischemic pain. In: Simpson B, editor. Electrical stimulation and relief of pain. New York: Elsevier; 2003. p. 161–82.Google Scholar
  15. 15.
    Linderoth B, Foreman R. Mechanisms of spinal cord stimulation in painful syndromes. Role of animal models. Pain Med. 2006;7 Suppl 1:14–26.CrossRefGoogle Scholar
  16. 16.
    Andréll P, Ekre O, Eliasson T, et al. Cost-effectiveness of spinal cord stimulation versus coronary artery bypass grafting in patients with severe angina pectoris – long-term results from the ESBY study. Cardiology. 2003;99:20–4.CrossRefPubMedGoogle Scholar
  17. 17.
    Levy RM. Spinal cord stimulation for medically refractory angina pectoris: can the therapy be resuscitated? Neuromodulation. 2011;14:1–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Garcia LA. Epidemiology and pathophysiology of lower extremity peripheral arterial disease. J Endovasc Ther. 2006;13:II3–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Golomb BA, Dang TT, Criqui MH. Peripheral arterial disease: morbidity and mortality implications. Circulation. 2006;114:688–99.CrossRefPubMedGoogle Scholar
  20. 20.
    Chochola M, Linhart A. Epidemiology of ischemic diseases of the lower extremities. Cas Lek Cesk. 2006;145:368–70.PubMedGoogle Scholar
  21. 21.
    Cook AW, Oygar A, Baggenstos P, et al. Vascular disease of extremities: electrical stimulation of spinal cord and posterior roots. N Y State J Med. 1976;76:366–8.PubMedGoogle Scholar
  22. 22.
    Klomp HM, Spincemaille GH, et al. Spinal-cord stimulation in critical limb ischaemia: a randomized trial ESES study group. Lancet. 1999;353(9158):1040–4.CrossRefPubMedGoogle Scholar
  23. 23.
    Ubbink DT, Spincemaille GH, et al. Microcirculatory investigations to determine the effect of spinal cord stimulation for critical leg ischemia: the Dutch multicenter randomized controlled trial. J Vasc Surg. 1999;30(2):236–44.CrossRefPubMedGoogle Scholar
  24. 24.
    Ubbink DT, Gersbach PA, et al. The best TcpO(2) parameters to predict the efficacy of spinal cord stimulation to improve limb salvage in patients with inoperable critical leg ischemia. Int Angiol. 2003;22(4):356–63.PubMedGoogle Scholar
  25. 25.
    Linderoth B, Meyerson BA. Spinal cord stimulation; techniques, indications and outcome. In: Lozano AM, Gildenberg PL, Tasker RR, editors. Textbook of stereotactic and functional neurosurgery. 2nd ed. Berlin/Heidelberg: McGraw Hill/Springer; 2009. p. 3288.Google Scholar
  26. 26.
    Linderoth B, Simpson BA, Myerson BA. Spinal cord and brain stimulation, Chap. 37. In: McMahon S, Kolzenburg M, editors. Wall and Melzack’s textbook of pain. 5th ed. Amsterdam: Elsevier; 2005. p. 1–20.Google Scholar
  27. 27.
    Linderoth B. Spinal cord stimulation in ischemia and ischemic pain. In: Horsch S, Clayes L, editors. Spinal cord stimulation III: an innovative method in the treatment of PVD and angina. Darmstadt: Steinkopff Verlag; 1995. p. 19–35.CrossRefGoogle Scholar
  28. 28.
    Foreman RD. The neurological basis for cardiac pain. In: Zucker IH, Gilmore JP, editors. Reflex control of the circulation. Boca Raton: CRC Press; 1991. p. 907.Google Scholar
  29. 29.
    Wu M, Linderoth B, Foreman RD. Putative mechanisms behind effects of spinal cord stimulation on vascular diseases: a review of experimental studies. Auton Neurosci. 2008;1381(1–20):9–23.CrossRefGoogle Scholar
  30. 30.
    Mannheimer C, Camici P, Chester MR, et al. The problem of chronic refractory angina report from the ESC Joint Study Group on the treatment of refractory angina. Eur Heart J. 2002;23:355–70.CrossRefPubMedGoogle Scholar
  31. 31.
    DeJongste MJL, Haaksma J, Hautvast RW, et al. Effects of spinal cord stimulation on daily life myocardial ischemia in patients with severe coronary artery disease. A prospective ambulatory ECG study. Eur Heart J. 1994;71:413–8.CrossRefGoogle Scholar
  32. 32.
    Mukherjee D, Bhatt DL, Roe MT, Patel V, Ellis SG. Direct myocardial revascularization and angiogenesis – how many patients might be eligible? Am J Cardiol. 1999;84(5):598–600.CrossRefPubMedGoogle Scholar
  33. 33.
    Mannheimer C, Augustinsson LE, Carlsson CA, et al. Epidural spinal electrical stimulation in severe angina pectoris. Br Heart J. 1988;59:56–61.CrossRefPubMedGoogle Scholar
  34. 34.
    Murphy DF, Giles KE. Dorsal column stimulation for pain relief from intractable angina. Pain. 1987;28:365–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Foreman RD. Mechanisms of cardiac pain. Annu Rev Physiol. 1999;61:143–67.CrossRefPubMedGoogle Scholar
  36. 36.
    de Vries J, Anthonio RL, Dejongste MJ, Jessurun GA, Tan ES, de Smet BJ, van den Heuvel AF, Staal MJ, Zijlstra F. The effect of electrical neurostimulation on collateral perfusion during acute coronary occlusion. BMC Cardiovasc Disord. 2007;7:18.CrossRefPubMedGoogle Scholar
  37. 37.
    Mannheimer C, Eliasson T, Andersson B, et al. Effects of spinal cord stimulation in angina pectoris induced by pacing and possible mechanisms of action. BMJ. 1993;307:477–80.CrossRefPubMedGoogle Scholar
  38. 38.
    Hautwast RW, Blanksma PK, DeJongste MJ, et al. Effect of spinal cord stimulation on myocardial blood flow assessed by positron emission tomography in patients with refractory angina pectoris. Am J Cardiol. 1996;77:462–7.CrossRefGoogle Scholar
  39. 39.
    Foreman RD, Linderoth B, Ardell JL, et al. Modulation of intrinsic cardiac neuronal activity by spinal cord stimulation: Implications for its therapeutic in angina pectoris. Cardiovasc Res. 2000;47(2):367–75.CrossRefPubMedGoogle Scholar
  40. 40.
    Eliasson T, Augustinsson LE, Mannheimer C. Spinal cord stimulation in severe angina pectoris: presentation of current studies, indications and practical experience. Pain. 1996;65:169–79.CrossRefPubMedGoogle Scholar
  41. 41.
    Hautvast RW, Ter Horst GJ, DeJong BM, et al. Relative changes in regional blood flow during spinal cord stimulation in patients with refractory angina pectoris. Eur J Neurosci. 1997;9:1178–83.CrossRefPubMedGoogle Scholar
  42. 42.
    Cardinal R, Page P, Vermeulen M, Bouchard C, Ardell JL, Foreman RD, Armour JA. Spinal cord stimulation suppresses bradycardias and atrial tachyarrhythmias induced by mediastinal nerve stimulation in dogs. Am J Physiol Regul Integr Comp Physiol. 2006;291:R1369–75.CrossRefPubMedGoogle Scholar
  43. 43.
    Foreman RD, DeJongste MJL, Linderoth B. Integrative control of cardiac function by cervical and thoracic spinal neurons. In: Armour JA, Ardell JL, editors. Basic and clinical neurocardiology. London: Oxford University Press; 2004. p. 153–86.Google Scholar
  44. 44.
    North RB, Kidd DH, et al. Spinal cord stimulation electrode design: a prospective, randomized, controlled trial comparing percutaneous with laminectomy electrodes: part II-clinical outcomes. Neurosurgery. 2005;57(5):990–6; discussion 990–6.CrossRefPubMedGoogle Scholar
  45. 45.
    Richard BN, Linderoth B. Spinal cord stimulation: chapter 96. In: Rathmell J, Ballantyne J, Fishman S, editors. Bonica’s management of pain. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2009. p. 16–48: chapter 95.Google Scholar
  46. 46.
    North RB. The glass is half full (commentary on the fallacy of 50% pain relief). Pain Forum. 1999;8:195–7.CrossRefGoogle Scholar

Copyright information

© American Academy of Pain Medicine 2013

Authors and Affiliations

  1. 1.Department of AnesthesiologyUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  2. 2.Department of PhysiologyUniversity of Oklahoma College of MedicineOklahoma CityUSA

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