Theory and Mechanisms of Action of Neuroaugmentation

  • Octavio Calvillo
  • Gabor B. Racz
  • Carl Noe


Neuroaugmentation techniques are important complementary treatments for the management of chronic pain. Spinal cord stimulation is used to treat patients with chronic radiculitis, complex regional pain syndrome, and ischemic pain.


Spinal cord stimulation Neuroaugmentation Neuropathic pain Ischemic pain Failed back syndrome 


  1. 1.
    Abram SE, Yi J, Fuchs A, Hogan QH. Permeability of injured and intact peripheral nerves and dorsal root ganglia. Anesthesiology. 2006;105(1):146–53.PubMedCrossRefGoogle Scholar
  2. 2.
    Aprison MH, Shank RP, Davidoff RA. A comparison of the concentration of glycine a transmitter suspect in different areas of the brain and spinal cord in seven different vertebrates. Comp Biochem Physiol. 1969;28:1345–55.PubMedCrossRefGoogle Scholar
  3. 3.
    Atkinson L, Sundaraj SR, Brooker C, et al. Recommendations for patient selection in spinal cord stimulation. J Clin Neurosci. 2011;18:1295–302.PubMedCrossRefGoogle Scholar
  4. 4.
    Bennett GY, Xie Y-Q. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 1988;33:87–107.PubMedCrossRefGoogle Scholar
  5. 5.
    Berger SI, Carter JC, Lowry OH. The distribution of glycine in the spinal neurons in the cat. J Neurophysiol. 1968;31:81–95.Google Scholar
  6. 6.
    Burke RE, Rudomin P, Vyklický L, Zajac III FE. Primary afferent depolarization and flexion reflexes produced by radiant heat stimulation of the skin. J Physiol. 1971;213(1):185–214.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Burnstock G, Sawynok J. Chapter 14 Adenosine Triphosphate and Adenosine Receptors and Pain. In: Beaulieu P, Lussier D, Porreca F, Dickenson AH, editors. Pharmacology of Pain. Seattle: IASP Press; 2010. p. 303–26.Google Scholar
  8. 8.
    Buyten JP, Smet I, Liem L, et al. Stimulation of dorsal root ganglia for the management of complex regional pain syndrome: a prospective case series. Pain Pract. 2014;15:208–16.PubMedCrossRefGoogle Scholar
  9. 9.
    Calvillo O, Esses S, Ponder C, et al. Neuroaugmentation in the management of sacroiliac pain: report of two cases. Spine. 1998;23:1069–72.PubMedCrossRefGoogle Scholar
  10. 10.
    Calvillo O, Racz G, Didie J, et al. Neuroaugmentation in the treatment of complex regional pain syndrome of the upper extremity. Acta Othop Belg. 1998;14:57–63.Google Scholar
  11. 11.
    Calvillo O, Madrid J, Rudomin P. Presynaptic depolarization of unmyelinated primary afferent fibers in the spinal cord of the cat. Neuroscience. 1982;7:1389–400.PubMedCrossRefGoogle Scholar
  12. 12.
    Calvillo O, Racz G, Didie J, Smith K. Neuroaugmentation in the treatment of complex regional pain syndrome of the upper extremity. Acta Orthop Belg. 1998;64(1):57–63.PubMedGoogle Scholar
  13. 13.
    Cavanaugh DJ, Lee H, Lo L, et al. Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli. Proc Natl Acad Sci U S A. 2009;106:9075–80.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Chen R, Pan HR. Spinal GABAB receptors mediate antinociceptive actions of cholinergic agents in normal and diabetic rats. Brain Res. 2003;965:67–74.PubMedCrossRefGoogle Scholar
  15. 15.
    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;73:87–95.PubMedCrossRefGoogle Scholar
  16. 16.
    De Ridder D, Vanneste S, Plazier M, et al. Burst spinal cord stimulation: toward a paresthesia-free pain suppression. Neurosurg. 2010;66:986–90.CrossRefGoogle Scholar
  17. 17.
    De Ridder D, Plazier M, Kamerling N, Menovsky T, Vanneste S. Burst spinal cord stimulation for limb and back pain. World Neurosurg. 2013;80(5):642–9 e1.PubMedCrossRefGoogle Scholar
  18. 18.
    Devor M. Ectopic discharges in Ab afferents as a source of neuropathic pain. Exp Brain Res. 2009;196:115–28.PubMedCrossRefGoogle Scholar
  19. 19.
    Devor M. Unexplained peculiarities of the dorsal root ganglion. Pain. 1999;82:27–35.CrossRefGoogle Scholar
  20. 20.
    Devor M, Obermeyer ML. Membrane differentiation in dorsal root ganglia and possible consequences for back pain. Neurosci Lett. 1984;51:341–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Devor M, Tal M. Nerve resection for the treatment of chronic neuropathic pain. Pain. 2014;155(6):1053–4.PubMedCrossRefGoogle Scholar
  22. 22.
    Daniel CA, MacDermott AB. Low-threshold primary afferent drive onto GABAergic interneurons in the superficial dorsal horn of the mouse. J Neurosci. 2009;29:686–95.CrossRefGoogle Scholar
  23. 23.
    Decosterd I, Woolf CJ. Spared nerve injury: animal model of persistent peripheral neuropathic pain. Pain. 2000;87:149–58.PubMedCrossRefGoogle Scholar
  24. 24.
    Dubuison D. Effect of dorsal-column stimulation on gelatinous and marginal neurons of cat spinal cord. J Neurosurg. 1989;70:257–65.CrossRefGoogle Scholar
  25. 25.
    Eldabe S, Raphael J, Thomson S, Manca A, de Belder M, Aggarwal R, Banks M, Brookes M, Merotra S, Adeniba R, Davies E, Taylor RS. The effectiveness and cost-effectiveness of spinal cord stimulation for refractory angina (RASCAL study): study protocol for a pilot randomized controlled trial. Trials. 2013;14:57.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Ephraim PL, Wegener ST, Mackenzie EJ, et al. Phantom pain, residual limb pain in amputees: results of a national survey. Arch Phys Med Rehabil. 2005;86:1910–9.PubMedCrossRefGoogle Scholar
  27. 27.
    El-Khoury C, Hawwa N, Baliki M, et al. Attenuation of neuropathic pain by segmental and supraspinal activation of the dorsal column nuclei in awake rats. Neuroscience. 2002;112:541–53.PubMedCrossRefGoogle Scholar
  28. 28.
    Feirabend HK, Choufoer S, Ploeger S, et al. Morphometry of human superficial dorsal root and dorsolateral column fibers: significance to cord stimulation. Brain. 2012;23(125):1137–49.Google Scholar
  29. 29.
    Franz DN, Iggo A. Dorsal root potentials and ventral root reflexes evoked by nonmyelinated fibers. Science. 1968;162:1140–2.PubMedCrossRefGoogle Scholar
  30. 30.
    Geurts JW, Smits H, Kemler MA, Brunner F, Kessels AG, van Kleef M. Spinal cord stimulation for complex regional pain syndrome type I: a prospective cohort study with long-term follow-up. Neuromodulation. 2013;16(6):523–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Goeller E, Slavin KV. Cervical spinal cord stimulation may prevent cerebral vasospasm by modulating sympathetic activity of the superior cervical ganglion at the lower cervical spinal level. Med Hypotheses. 2009;73:410–3.CrossRefGoogle Scholar
  32. 32.
    Guan Y. Spinal cord stimulation: neurophysiological and neurochemical mechanisms of action. Curr Pain Headache Rep. 2012;16:217–25.PubMedCrossRefGoogle Scholar
  33. 33.
    Gybels J, Kupers R. Central and peripheral electrical stimulation of the nervous system in the treatment of chronic pain. Acta Neurochir Suppl (Wien). 1987;38:64–75.CrossRefGoogle Scholar
  34. 34.
    Hauvast RW, DeJonste MJL, Staal MJ. Spinal cord stimulation in chronic intractable angina pectoris: a randomized, controlled efficacy study. Am Heart J. 1998;136:1114–20.CrossRefGoogle Scholar
  35. 35.
    Hawkes CH, Fawcet D, Cooke ED. Dorsal column stimulation in multiple sclerosis: effects on bladder, leg blood flow and peptides. Appl Neurophysiol. 1981;41:62–70.Google Scholar
  36. 36.
    Heavner JE, Racz G, Diede JM. Peripheral nerve stimulation: current concepts. In: Waldman SD, Winnie AP, editors. Interventional pain management. Philadelphia: WB Saunders; 1996. p. 423–4.Google Scholar
  37. 37.
    Heavner JE, Racz G, Raj PP. Peripheral nerve stimulation: current concepts. In: Waldman SD, editor. Interventional pain management. 2nd ed. Philadelphia: W.B. Saunders Company; 2001. p. 588–92.Google Scholar
  38. 38.
    Herdege T, Fiallos-Estrade CE, Schmid W, et al. The transcription factors c-Jun, Jun-D and CREB, but not c-Fos and KROX-24 are differentially regulated in axotomized neurons following transection of the sciatic nerve. Brain Res Mol Brain Res. 1992;14:155–65.CrossRefGoogle Scholar
  39. 39.
    Honmou O, Utzchneider DA, Rizzo MA, et al. Delayed depolarization and slow sodium currents in cutaneous afferents. J Neurophysiol. 1994;71:1627–41.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Holsheimer J, Wesselink WA. Computer modeling of spinal cord stimulation and its contribution to therapeutic efficacy. Spinal Cord. 1998;36:531–40.PubMedCrossRefGoogle Scholar
  41. 41.
    Kapural L, Deer T, Yakovlev A, Bensitel T, et al. Technical aspects of spinal cord stimulation for managing chronic visceral abdominal pain: the results from a national survey. Pain Med. 2010;11:685–91.PubMedCrossRefGoogle Scholar
  42. 42.
    Kapural L, Narouze SN, Janicki T, et al. Spinal cord stimulation is an effective treatment for chronic intractable visceral pain. Pain Med. 2006;7:440–3.PubMedCrossRefGoogle Scholar
  43. 43.
    Kapural L, Rakic M. Spinal cord stimulation for chronic visceral pain secondary to chronic non-alcoholic pancreatitis. J Clin Gastroenterol. 2008;42:750–1.PubMedCrossRefGoogle Scholar
  44. 44.
    Khasabov SG, Ghilardin JR, Mantyh PW, et al. Spinal neurons that express NK-1 receptors modulate descending controls that project through the dorsolateral funiculus. J Neurophysiol. 2005;93:998–1006.PubMedCrossRefGoogle Scholar
  45. 45.
    Klein JP, Tendi EA, Dib-Hajj SD, et al. Patterned electrical activity modulates sodium channel expression in sensory neurons. J Neurosci Res. 2003;74:192–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Krames E. The dorsal root in chronic pain and as target for neuromodulation. Neuromodulation. 2015;18:24–32.PubMedCrossRefGoogle Scholar
  47. 47.
    Kumar K, Rizvi S, Bnurs SB. Spinal cord stimulation is effective in management of complex regional pain syndrome I: fact or fiction. Neurosurgery. 2011;69(3):566–78; discussion 5578–80. doi.  10.1227/NEU.0b013e3182181e60.PubMedCrossRefGoogle Scholar
  48. 48.
    Jeon Y, Hub BK. Spinal cord stimulation for chronic pain. Ann Acad Med Singapore. 2009;38:998–1003.PubMedGoogle Scholar
  49. 49.
    Jeon Huh 2009; Yakhnista V, Linderoth B, et al. Spinal cord stimulation attenuates dorsal horn hyperexcitability in a rat model of mononeuropathy. Pain. 1999;79:223–33Google Scholar
  50. 50.
    Kumar K, Taylor RS, Jacques L, 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;132:179–88.PubMedCrossRefGoogle Scholar
  51. 51.
    Kumar K, Taylor RS, Jacques L, 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;63:762–70.PubMedCrossRefGoogle Scholar
  52. 52.
    Liem L, Russo M, Huygen FJ. A multicenter, prospective trial to assess the safety and performance of spinal modulation dorsal root ganglion neurostimulator system in the treatment of chronic pain. Neuromodulation. 2013;16:471–82.PubMedCrossRefGoogle Scholar
  53. 53.
    Lind G, Schechtmann G, Winter J, Meyerson BA, Linderoth B. Baclofen-enhanced spinal cord stimulation and intrathecal baclofen alone for neuropathic pain: Long-term outcome of a pilot study. Eur J Pain. 2008;12(1):132–6. Epub 2007 May 1.PubMedCrossRefGoogle Scholar
  54. 54.
    Lind G, Winter J, Lindroth B, Hellstrom PM. Therapeutic value of spinal cord stimulation in irritable bowel syndrome: a randomized crossover pilot study. Am J Physiol Regul Integr Comp Physiol. 2015;308:R887–94.PubMedCrossRefGoogle Scholar
  55. 55.
    Ling G, Linderoth B. Pharmacological enhanced spinal cord stimulation for pain: an evolving strategy. Pain Manag. 2011;1(5):441–9.CrossRefGoogle Scholar
  56. 56.
    Meyerson B, Brodin E, Linderoth B. Possible neurohumeral mechanisms in CNS stimulation for pain suppression. Appl Neurophysiol. 1985;48:175–80.PubMedGoogle Scholar
  57. 57.
    Mannheimmer C, Eliasson T, Andersson B, et al. Effects of spinal cord stimulation in angina pectoris induced by pacing and possible mechanism of action. BMJ. 1993;307:477–80.CrossRefGoogle Scholar
  58. 58.
    Mekhail NA, Mathews M, Nageeb F, et al. Clinical applications of neurostimulation: forty years later. Pain Pract. 2010;10:103–12.PubMedCrossRefGoogle Scholar
  59. 59.
    Mendell LM, Wall PD. Presynaptic hyperpolarization: a role for fine afferent fibres. The Journal of Physiology. 1964;172(2):274–94.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Meyerson BA, Linderoth B. Mode of action of spinal cord stimulation in neuropathic pain. J Pain Symptom Manage. 2006;31(4 Suppl):S6–12.PubMedCrossRefGoogle Scholar
  61. 61.
    Leveque JC, Villavicencio AT, Bulsara KR, et al. Spinal cord stimulation for failed back surgery syndrome. Neuromodulation. 2001;4:1–9.PubMedCrossRefGoogle Scholar
  62. 62.
    Levin BE, Hubschmann OR. Dorsal column stimulation: effect on human cerebrospinal fluid and plasma catecholamine. Neurology. 1980;30:65–70.PubMedCrossRefGoogle Scholar
  63. 63.
    Lind G, Schechtmann G, Winter J, et al. Drug-enhanced spinal stimulation for pain: a new strategy. Acta Neurochir Suppl. 2007;97:57–63.PubMedGoogle Scholar
  64. 64.
    Linderoth B, Gazelius B, Frank J, et al. Dorsal column stimulation induces release of serotonin and substance P in the cat dorsal horn. Neurosurgery. 1992;31:1289–96.Google Scholar
  65. 65.
    Ming GL, Henley J, Tessier-Lavigne M, et al. Electrical modulates growth cone guidance by diffusible factors. Neuron. 2001;29:441–52.PubMedCrossRefGoogle Scholar
  66. 66.
    Mironer YE, Hutcheson JK, Satterwaite JR, et al. Prospective, two part study of the interaction between spinal cord stimulation and peripheral field stimulation in patients with low back pain: development of anew spinal-peripheral neurostimulation method. Neuromodulation. 2011;14:151–4.PubMedCrossRefGoogle Scholar
  67. 67.
    North RB, Kidd DH, Farrokhi F, et al. Spinal cord stimulation versus repeated lumbosacral spine surgery for chronic pain: a randomized, controlled trial. Neurosurgery. 2005;56:98–106.PubMedGoogle Scholar
  68. 68.
    Oakley JC, Prager JP. Spinal cord stimulation: mechanism of action. Spine. 1976;2002:2574–83.Google Scholar
  69. 69.
    Oakley JC, Prager JP. Spinal cord stimulation: mechanism of action. Spine. 2002;1976:2574–83.CrossRefGoogle Scholar
  70. 70.
    Prasad A, Sahin M. Characterization of neural activity recorded from the descending tracts of the rat spinal cord. Frontiers in Neuroscience. 2010;4:21. doi: 10.3389/fnins.2010.00021.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Perruchoud C, Eldabe S, Batterham AM, Madzinga G, Brookes M, Durrer A, Rosato M, Bovet N, West S, Bovy M, Rutschmann B, Gulve A, Garner F, Buchser E. Analgesic efficacy of high-frequency spinal cord stimulation: a randomized double-blind placebo-controlled study. Neuromodulation. 2013;16(4):363–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Racz GB, McCarron RF, Tallboys P. Percutaneous dorsal column stimulator for chronic back pain. Spine. 1989;14:1–4.PubMedCrossRefGoogle Scholar
  73. 73.
    Raslan AM, McCartney S, Burchiel KJ. Management of chronic severe pain: spinal neuromodulatory and neuroablative approaches. Acta Neurochir Suppl. 2007;97(Pt 1):33–41.PubMedGoogle Scholar
  74. 74.
    Rees H, Roberts MH. Activation of cells in the anterior pretectal nucleus by dorsal column stimulation in the rat. J Physiol. 1989;417:361–73.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Ren B, Linderoth B, Meyerson BA. Effects of spinal cord stimulation on the flexor reflex and involvement of supraspinal mechanisms: an experimental study in mononeuropathic rats. J Neurosurg. 1996;84:244–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Rigoard P, Desai MJ, North RB, Taylor RS, Annemans L, Greening C, Tan Y, Van den Abeele C, Shipley J, Kumar K. Spinal cord stimulation for predominant low back pain in failed back surgery syndrome: study protocol for an international multicenter randomized controlled trial (PROMISE study). Trials. 2013;14:376.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Parker JL, Karantonis DM, Single PS, et al. Compound action potentials recorded in the human spinal cord during neurostimulation for pain relief. Pain. 2012;153:593–601.PubMedCrossRefGoogle Scholar
  78. 78.
    Saade NE, Tabet MS, Soueidan SA, Bitar M, et al. Supraspinal modulation of nociception in awake rats by stimulation of the dorsal column nuclei. Brain Res. 1986;369:307–10.PubMedCrossRefGoogle Scholar
  79. 79.
    Sadee N, Barchini J, Tchahahian S, et al. The role of the dorsolateral funiculi in the pain relieving effect of spinal cord stimulation: a study in a rat model of neuropathic pain. Exp Brain Res. 2015;233:1041–52.CrossRefGoogle Scholar
  80. 80.
    Saade N, Atweh AF, Tabet MS, et al. Inhibition of nociceptive withdrawal flexion reflexes through a dorsal column-brainstem spinal loop. Brain Res. 1985;335:306–8.PubMedCrossRefGoogle Scholar
  81. 81.
    Sapunar D, Kostic S, Banozic A, et al. Dorsal root ganglion-a potential new therapeutic target for neuropathic pain. J Pain Res. 2012;5:31–8.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Sapunar D, Ljubkovic M, Lirk P, et al. Distinct membrane effects of spinal nerve ligation on injured and adjacent dorsal root ganglion neurons in rats. Anesthesiology. 2005;103(2):360–76.PubMedCrossRefGoogle Scholar
  83. 83.
    Schechtmann G, Lind G, Winter J, et al. Intrathecal clonidine and baclofen enhance the pain-relieving effect of spinal cord stimulation: a comparative placebo-controlled randomized trial. Neurosurgery. 2010;67:173–81.PubMedCrossRefGoogle Scholar
  84. 84.
    Schechtmann G, Lind G, Winter J, et al. Cholinergic mechanisms involved in the pain relieving effect of spinal cord stimulation in a model of neuropathy. Pain. 2008;139:136–45.PubMedCrossRefGoogle Scholar
  85. 85.
    Schoffingger D, Heinke B, Sommer C, et al. Physiological properties of spinal lamina II GABAergic neurons in mice following peripheral nerve injury. J Physiol. 2006;577:869–78.CrossRefGoogle Scholar
  86. 86.
    Schu S, Slotty PJ, Bara G, von Knop M, Edgar D, Vesper J. A prospective, randomised, 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(5):443–50.PubMedCrossRefGoogle Scholar
  87. 87.
    Schu S, Gulve A, Dave EL, et al. Spinal cord stimulation for groin pain-a retrospective review. Pain Pract. 2015;15:293–9.PubMedCrossRefGoogle Scholar
  88. 88.
    Schecter R, Yang F, Xu Q, Young-Kuan C, 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.CrossRefGoogle Scholar
  89. 89.
    Schultz DM, Webster L, Kosec P, et al. Sensor-driven position-adaptive spinal cord stimulation for chronic pain. Pain Physician. 2012;15:1–12.PubMedGoogle Scholar
  90. 90.
    Shealy CN, Mortimer JT, Reswick JB. Electrical inhibition of pain by stimulation of the dorsal columns: preliminary clinical report. Anesth Anal. 1967;46:489–91.Google Scholar
  91. 91.
    Shetter AG, Racz GB, Lewis R, Heavner JE. Peripheral nerve stimulation. In: North R, Levy R, editors. Neurosurgical management of pain. New York: Springer; 1997. p. 261–70.CrossRefGoogle Scholar
  92. 92.
    Silberstein SD, Dodick DW, Saper J, et al. Safety and efficacy of peripheral nerve stimulation of the occipital nerves for the management of chronic migraine: results from a randomized, multicenter, double-blinded, controlled study. Cephalalgia. 2012;32:1165–79.PubMedCrossRefGoogle Scholar
  93. 93.
    Sisken BF, Walker J, Orgel M. Prospects on clinical applications of electrical stimulation for nerve regeneration. J Cell Biochem. 1993;51:404–9.PubMedCrossRefGoogle Scholar
  94. 94.
    Skaribas I, Calvillo O, Delikanis-Skaribas E. Occipital peripheral nerve stimulation in the management of chronic intractable occipital neuralgia with neurofibromatosis type 1: a case report. J Med Case Reports. 2011;5:174–6.PubMedCentralCrossRefGoogle Scholar
  95. 95.
    Slavin KV, Vannemreddy PS, Goellner E, et al. Use of cervical spinal cord stimulation in treatment and prevention of arterial vasospasm after aneurysmal hemorrhage. Neuroradiol J. 2011;1:139–43.Google Scholar
  96. 96.
    Slavin K. Spinal stimulation for pain: future applications. Neurotherapeutics. 2014;11:535–42.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Song Z, Ansah OB, Meyerson BA, et al. Exploration of supraspinal mechanisms in effects of spinal cord stimulation: role of the locus coeruleus. Neuroscience. 2013;253:426–34.PubMedCrossRefGoogle Scholar
  98. 98.
    Song Z, Ultenius C, Meyerson BA, et al. Pain relief by spinal cord stimulation involves serotonergic mechanisms: an experimental study in a rat model of mononeuropathy. Pain. 2009;147:241–8.PubMedCrossRefGoogle Scholar
  99. 99.
    Song Z, Meyerson BA, Linderoth B. Spinal 5-HT receptors that contribute to the pain-relieving effects of spinal cord stimulation in a rat model of neuropathy. Pain. 2011;152:1666–73.PubMedCrossRefGoogle Scholar
  100. 100.
    Song Z, Meyerson BA, Linderoth B. Muscarinic receptor activation potentiates the effect of spinal cord stimulation on pain-related behavior in rats with mononeuropathy. Neurosci Lett. 2008;436:7–12.PubMedCrossRefGoogle Scholar
  101. 101.
    Simpson RK, Robertson CS, Goodman C. Glycine: a potential mediator of electrically induced pain modification. Biomed Lett. 1993;48:193–207.Google Scholar
  102. 102.
    Simpson RK, Gondo M, Robertson CS, et al. Reduction in the mechanoreceptor response by intrathecal administration of glycine and related compounds. Neurochem Res. 1996;21:1221–6.PubMedCrossRefGoogle Scholar
  103. 103.
    Slangen R, Schaper NC, Faber CG, Joosten EA, Dirksen CD, van Dongen RT, et al. Spinal cord stimulation and pain relief in painful diabetic peripheral neuropathy: a prospective two-center randomized controlled trial. Diabetes Care. 2014;37(11):3016–24.PubMedCrossRefGoogle Scholar
  104. 104.
    Stiller CO, Cui JG, O’Connor WT, et al. Release of gamma-aminobutyric acid in the dorsal horn and suppression of tactile allodynia by spinal cord stimulation in mononeuropathic rats. Neurosurgery. 1996;39:367–74.PubMedCrossRefGoogle Scholar
  105. 105.
    Sukhotinsky I, Ben-Dor E, Raver P, et al. Key role of the dorsal root ganglion in neuropathic tactile hypersensibility. Eur J Pain. 2004;8:135–43.PubMedCrossRefGoogle Scholar
  106. 106.
    Tiede J, Brown L, Gekht G, et al. Novel spinal cord stimulation parameters in patients with predominantly back pain. Neuromodulation. 2013;16:370–5.PubMedCrossRefGoogle Scholar
  107. 107.
    Tomycz ND, Deibert CP, Moossy JJ. Cervicomedullary junction spinal cord stimulation for head and facial pain. Headache. 2011;51:418–25.PubMedCrossRefGoogle Scholar
  108. 108.
    Torre-Amione G, Alo K, Estep JD, Valderrabano M, Khalil N, Farazi TG, et al. Spinal cord stimulation is safe and feasible in patients with advanced heart failure: early clinical experience. Eur J Heart Fail. 2014;16(7):788–95.PubMedCrossRefGoogle Scholar
  109. 109.
    Van Buyten JP, Al-Kaiisy A, Palmisani S, et al. High frequency spinal cord stimulation for the treatment of chronic back pain: results of a prospective multicenter European clinical study. Neuromodulation. 2013;16:59–66.PubMedCrossRefGoogle Scholar
  110. 110.
    Van Ejis F, Stanton-Hicks M, Van Zundert J, et al. Evidence-based interventional pain medicine according to clinical diagnosis. 16 complex regional pain syndrome. Pain Pract. 2011;11:70–87.CrossRefGoogle Scholar
  111. 111.
    Vaso A, Haim-Moshe A, Gjika A, Zahaj S, Zhurda T, Vyshka G, et al. Peripheral nervous system origin of phantom limb pain. Pain. 2014;155(7):1384–91.PubMedCrossRefGoogle Scholar
  112. 112.
    Viswanathan A, Phan PC, Burton AW. Use of spinal cord stimulation in the treatment in the treatment of phantom limb pain: case series and review of the literature. Pain Pract. 2010;10(5):479–84.PubMedCrossRefGoogle Scholar
  113. 113.
    Washburn S, Catlin R, Bethel K, Canlas B. Patient-perceived differences between constant current and constant voltage spinal cord stimulation systems. Neuromodulation. 2014;17(1):28–35.PubMedCrossRefGoogle Scholar
  114. 114.
    Watkins LR, Milligan ED, Maier SF. Glial activation: a driving force for pathological pain. Trends Neurosci. 2001;24:450–5.PubMedCrossRefGoogle Scholar
  115. 115.
    Watson CP, Peter CN, Mackinnon SE, Dostrovsky JO, Jonathan O, Bennett GJ, et al. Nerve resection, crush and re-location relieve complex regional pain syndrome type II: a case report. Pain. 2014;155(6):1168–73.PubMedCrossRefGoogle Scholar
  116. 116.
    Wang YY, Wu SX, Wang W, et al. Effects of c-fos antisense oligodeoxynucleotide on 5HT-induced upregulation of preprodynorphin, proenkephalin and glutamic acid decarboxylase mRNA expression in cultured rat spinal dorsal horn neurons. Biochem Biophys Res Commun. 2003;309:631–6.PubMedCrossRefGoogle Scholar
  117. 117.
    Weiner RL, Reed KL. Peripheral neurostimulation for control of intractable occipital neuralgia. Neuromodulation. 1999;3:217–21.CrossRefGoogle Scholar
  118. 118.
    Wolter T, Kieselbach K. Spinal cord stimulation for Raynaud’s syndrome: long-term alleviation of bilateral pain with a single cervical lead. Neuromodulation. 2011;14:229–33.PubMedCrossRefGoogle Scholar
  119. 119.
    Wu G, Ringkamp M, Murrison BB. Degeneration of myelinated afferent fibers induces spontaneous activity in uninjured C-fiber afferents. J Neurosci. 2002;22:7746–53.PubMedGoogle Scholar
  120. 120.
    Xiao HS, Huang QH, Zhang FX. Identification gene expression profile of dorsal root in the rat peripheral axotomy model of neuropathic pain. Proc Natl Acad Sci U S A. 2002;99:8360–5.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Zuo C, Yang X, Wang Y, et al. A digital wireless system for closed-loop inhibition of nociceptive signals. J Neural Eng. 2012;9:056010.PubMedCrossRefGoogle Scholar
  122. 122.
    Zimmermann M. Dorsal root potentials after C fiber stimulation. Science. 1968;160:896–8.PubMedCrossRefGoogle Scholar
  123. 123.
    Zipes DP, Svorkdal N, Berman D, Boortz-Marx R, Henry T, Lerman A, Irwin C. Spinal cord stimulation therapy for patients with refractory angina who are not candidates for revascularization. Neuromodulation. 2012;15(6):550–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of AnesthesiologyMethodist HospitalHoustonUSA
  2. 2.Department of AnesthesiologyTexas Tech University Health Sciences CenterLubbockUSA
  3. 3.Department of Anesthesiology and Pain ManagementUniversity of Texas Southwestern Medical CenterDallasUSA

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