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Review of the Uses of Vagal Nerve Stimulation in Chronic Pain Management

  • Neuromodulation (M Gofeld, Section Editor)
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Abstract

Recent human and animal studies provide growing evidence that vagal nerve stimulation (VNS) can deliver strong analgesic effects in addition to providing therapeutic efficacy in the treatment of refractory epilepsy and depression. Analgesia is potentially mediated by vagal afferents that inhibit spinal nociceptive reflexes and transmission and have strong anti-inflammatory properties. The purpose of this review is to provide pain practitioners with an overview of VNS technology and limitations. It specifically focuses on clinical indications of VNS for various chronic pain syndromes, including fibromyalgia, pelvic pain, and headaches. We also present potential mechanisms for VNS modulation of chronic pain by reviewing both animal and human studies.

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References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Randich A, Gebhart GF. Vagal afferent modulation of nociception. Brain Res Brain Res Rev. 1992;17:77–99.

    Article  CAS  PubMed  Google Scholar 

  2. Ren K, Zhuo M, Randich A, Gebhart GF. Vagal afferent stimulation-produced effects on nociception in capsaicin-treated rats. J Neurophysiol. 1993;69:1530–40.

    CAS  PubMed  Google Scholar 

  3. Sylvie M, Schoenen J. Pain control by vagus nerve stimulation: from animal to man…and back. Acta Neurol Belg. 2005;105:62–7.

    Google Scholar 

  4. Kirchner A, Birklein F, Stefan H, Handwerker HO. Left vagus nerve stimulation suppresses experimentally induced pain. Neurology. 2000;55:1167–71.

    Article  CAS  PubMed  Google Scholar 

  5. Ness TJ, Fillingim RB, Randich A, Backensto EM, Faught E. Low intensity vagal nerve stimulation lowers human thermal pain thresholds. Pain. 2000;86:81–5.

    Article  CAS  PubMed  Google Scholar 

  6. Ness TJ, Randich A, Fillingim RB, Faught E, Backensto EM. Left vagus nerve stimulation suppresses experimentally induced pain. Neurology. 2001;56:985–6.

    Article  CAS  PubMed  Google Scholar 

  7. Sedan O, Sprecher E, Yarnitsky D. Vagal stomach afferents inhibit somatic pain perception. Pain. 2005;113:354–9.

    Article  PubMed  Google Scholar 

  8. Ben-Menachem E, Revesz D, Simon BJ, Silberstein S. Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Eur J Neurol. 2015;22:1260–8. Excellent review on vagal nerve stimulators and their clinical utility.

    Article  CAS  PubMed  Google Scholar 

  9. Hatton KW, McLarney JT, Pittman T, Fahy BG. Vagal nerve stimulation: overview and implications for anesthesiologists. Anesth Analg. 2006;103:1241–9.

    Article  PubMed  Google Scholar 

  10. Krahl SE. Vagus nerve stimulation for epilepsy: a review of the peripheral mechanisms. Surg Neurol Int. 2012;3:S47–52.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Foley JO, Dubois F. Quantitative studies of the vagus nerve in the cat, I. The ratio of sensory and motor studies. J Comp Neurol. 1937;67:49–67.

    Article  Google Scholar 

  12. Ricardo JA, Koh ET. Anatomical evidence of direct projections from the nucleus of the solitary tract to the hypothalamus, amygdala, and other forebrain structures in the rat. Brain Res. 1978;153:1–26.

    Article  CAS  PubMed  Google Scholar 

  13. Morest DK. Experimental study of the projections of the nucleus of the tractus solitarius and the area postrema in the cat. J Comp Neurol. 1967;130:277–300.

    Article  CAS  PubMed  Google Scholar 

  14. Cecheto DF. Central representation of visceral function. Fed Proc. 1987;46:17–23.

    Google Scholar 

  15. Krahl SE, Clark KB, Smith DC, Browning RA. Locus coeruleus lesions suppress the seizure-attenuating effects of vagus nerve stimulation. Epilepsia. 1998;39:709–14.

    Article  CAS  PubMed  Google Scholar 

  16. Matheny RG, Shaar CJ. Vagus nerve stimulation as a method to temporarily slow or arrest the heart. Ann Thorac Surg. 1997;63(6 Suppl):S28–9.

    Article  CAS  PubMed  Google Scholar 

  17. Ardell JL, Randall WC. Selective vagal innervation of sinoatrial and atrioventricular nodes in canine heart. Am J Physiol. 1986;251(4 Pt 2):H764–73.

    CAS  PubMed  Google Scholar 

  18. Ruffoli R, Giorgi FS, Pizzanelli C, Murri L, Paparelli A, Fornai F. The chemical neuroanatomy of vagus nerve stimulation. J Chem Neuroanat. 2011;42:288–96.

    Article  CAS  PubMed  Google Scholar 

  19. Berthoud HR, Neuhuber WL. Functional and chemical anatomy of the afferent vagal system. Auton Neurosci. 2000;85:1–17.

    Article  CAS  PubMed  Google Scholar 

  20. Fahy BG. Intraoperative and perioperative complications with a vagus nerve stimulation device. J Clin Anesth. 2010;22:213–22. Excellent evidence based review on vagus nerve stimulation devices and their intraoperative and perioperative complications.

    Article  PubMed  Google Scholar 

  21. Bauman JA, Ridgway EB, Devinsky O, Doyle WK. Subpectoral implantation of the vagus nerve stimulator. Neurosurgery. 2006;58(4 Suppl 2):ONS-322–5.

    Google Scholar 

  22. Milby AH, Halpern CH, Baltuch GH. Vagus nerve stimulation for epilepsy and depression. Neurotherapeutics. 2008;5:75–85.

    Article  PubMed  Google Scholar 

  23. Ben-Menachem E, Mañon-Espaillat R, Ristanovic R, et al. Vagus nerve stimulation for treatment of partial seizures: a controlled study of effect on seizures. First International Vagus Nerve Stimulation Study Group. Epilepsia. 1994;35:616–26.

    Article  CAS  PubMed  Google Scholar 

  24. Physician’s Manual VNS Therapy Pulse Model 102 Generator and VNS Therapy Pulse Duo Model 102R Generator, May 2003, U.S. Domestic Version. Houston, TX: Cyberonics, Inc.; 2004. Available at: http://www.vnstherapy.com/manuals.

  25. Cyberonics Inc. 2013 Annual Report. http://ir.cyberonics.com/annuals.cfm (accessed 03/05/2014).

  26. Vagus Nerve Stimulation Study Group. A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. Neurology. 1995;45:224–30.

    Article  Google Scholar 

  27. Uthman BM, Wilder BJ, Penry JK, et al. Treatment of epilepsy by stimulation of the vagus nerve. Neurology. 1993;43:1338–45.

    Article  CAS  PubMed  Google Scholar 

  28. Rush AJ, Marangell LB, Sackeim HA, et al. Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biol Psychiatry. 2005;58:347–54.

    Article  PubMed  Google Scholar 

  29. Rush AJ, Sackeim HA, Marangell LB, et al. Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study. Biol Psychiatry. 2005;58:355–63.

    Article  PubMed  Google Scholar 

  30. VNS Therapy System Physician’s Manual. Houston, TX: Cyberonics Inc.; 2013. http://dynamic.cyberonics.com/manuals/ (accessed 01/05/2015).

  31. Sadler RM, Purdy RA, Rahey S. Vagal nerve stimulation aborts migraine in patient with intractable epilepsy. Cephalalgia. 2002;22:482–4.

    Article  CAS  PubMed  Google Scholar 

  32. Mauskop A. Vagus nerve stimulation relieves chronic refractory migraine and cluster headaches. Cephalalgia. 2005;25:82–6.

    Article  CAS  PubMed  Google Scholar 

  33. Schwartz PJ, De Ferrari GM, Sanzo A, et al. Long term vagal stimulation in patients with advanced heart failure: first experience in man. Eur J Heart Fail. 2008;10:884–91.

    Article  PubMed  Google Scholar 

  34. Merrill CA, Jonsson MA, Minthon L, et al. Vagus nerve stimulation in patients with Alzheimer’s disease: additional follow-up results of a pilot study through 1 year. J Clin Psychiatry. 2006;67:1171–8.

    Article  CAS  PubMed  Google Scholar 

  35. Sjogren MJ, Hellstrom PT, Jonsson MA, Runnerstam M, Silander HC, Ben-Menachem E. Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer’s disease: a pilot study. J Clin Psychiatry. 2002;63:972–80.

    Article  PubMed  Google Scholar 

  36. George MS, Ward Jr HE, Ninan PT, et al. A pilot study of vagus nerve stimulation (VNS) for treatment-resistant anxiety disorders. Brain Stimul. 2008;1:112–21.

    Article  CAS  PubMed  Google Scholar 

  37. Roslin M, Kurian M. VNS in the treatment of morbid obesity. In: Schacter SC, Schmidt D, editors. VNS. London: Martin-Dunitz; 2012. p. 113–21.

    Google Scholar 

  38. Ben-Menachem E. Vagus-nerve stimulation for the treatment of epilepsy. Lancet Neurol. 2002;1:477–82.

    Article  PubMed  Google Scholar 

  39. Tatum WO, Moore DB, Stecker MM, et al. Ventricular asystole during vagus nerve stimulation for epilepsy in humans. Neurology. 1999;52:1267–9.

    Article  PubMed  Google Scholar 

  40. Ali II, Pirzada NA, Kanjwal Y, et al. Complete heart block with ventricular asystole during left vagus nerve stimulation for epilepsy. Epilepsy Behav. 2004;5:768–71.

    Article  PubMed  Google Scholar 

  41. Ardesch JJ, Buschman HP, van der Burgh PH, Wagener-Schimmel LJ, van der Aa HE, Hageman G. Cardiac responses of vagus nerve stimulation: intraoperative bradycardia and subsequent chronic stimulation. Clin Neurol Neurosurg. 2007;109:849–52.

    Article  CAS  PubMed  Google Scholar 

  42. Schuurman PR, Beukers RJ. Ventricular asystole during vagal nerve stimulation. Epilepsia. 2009;50:967–8.

    Article  PubMed  Google Scholar 

  43. Ben-Menachem E, Hellstrom K, Waldton C, Augustinsson LE. Evaluation of refractory epilepsy treated with vagus nerve stimulation for up to 5 years. Neurology. 1999;52:1265–7.

    Article  CAS  PubMed  Google Scholar 

  44. Husain MM, Stegman D, Trevino K. Pregnancy and delivery while receiving vagus nerve stimulation for the treatment of major depression: a case report. Ann Gen Psychiatry. 2005;4:16.

    Article  PubMed Central  PubMed  Google Scholar 

  45. CardioFit Pilot Study. Promising results from the CardioFit pilot study. http://www.biocontrol-medical.com/health_pros.php?ID=23.

  46. NEMOS t-VNS for treatment of drug-resistant epilepsy. http://cerbomed.com/upload/Brochure_Epilepsy_Patients_EN.pdf (accessed 01/29/2014).

  47. Busch V, Zeman F, Heckel A, Menne F, Ellrich J, Eichhammer P. The effect of transcutaneous vagus nerve stimulation on pain perception—an experimental study. Brain Stimul. 2013;6:202–9.

    Article  PubMed  Google Scholar 

  48. Nesbitt AD, Marin JCA, Tomkins E, Ruttledge MH, Goadsby PJ. Non-invasive vagus nerve stimulation for the treatment of cluster headache: a cohort series with extended follow-up. Presented at Biennial World Congress of the International Neuromodulation Society, 8–13 June 2013, Berlin, Germany.

  49. Goadsby P, Lipton R, Cady R, Mauskop A, Grosberg B. Non-invasive vagus nerve stimulation (nVNS) for acute treatment of migraine: an open-label pilot study [abstract S40.004]. Presented at Annual Meeting of the American Academy of Neurology, 16–23 March 2013, San Diego, CA.

  50. Nesbitt AD, Marin JCA, Tomkins E, Ruttledge MH, Goadsby PJ. Non-invasive vagus nerve stimulation for the treatment of cluster headache: a cohort study [abstract P141]. Cephalalgia. 2013;33:107.

  51. Goadsby PJ, Grosberg BM, Mauskop A, Cady R, Simmons KA. Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study. Cephalalgia. 2014;34:986–93.

    Article  CAS  PubMed  Google Scholar 

  52. Moscato D, Moscato FR. Treatment of chronic migraine by means of vagal stimulator [abstract]. J Headache Pain. 2013;14(Suppl):56–7.

    Google Scholar 

  53. Zalvan C, Sulica L, Wolf S, Cohen J, Gonzalez-Yanes O, Blitzer A. Laryngopharyngeal dysfunction from the implant vagal nerve stimulator. Laryngoscope. 2003;113:221–5.

    Article  PubMed  Google Scholar 

  54. Amark P, Stödberg T, Wallstedt L. Late onset bradyarrhythmia during vagus nerve stimulation. Epilepsia. 2007;48:1023–4.

    Article  PubMed  Google Scholar 

  55. Iriarte J, Urrestarazu E, Alegre M, et al. Late-onset periodic asystolia during vagus nerve stimulation. Epilepsia. 2009;50:928–32.

    Article  PubMed  Google Scholar 

  56. Handforth A, DeGiorgio CM, Schachter SC, et al. Vagus nerve stimulation therapy for partial-onset seizures: a randomized active control trial. Neurology. 1998;51:48–55.

    Article  CAS  PubMed  Google Scholar 

  57. Lundy DS, Casiano RR, Landy HJ, Gallo J, Gallo B, Ramsey RE. Effects of vagal nerve stimulation on laryngeal function. J Voice. 1993;7:359–64.

    Article  CAS  PubMed  Google Scholar 

  58. Lundgren J, Ekberg O, Olsson R. Aspiration: a potential complication to vagus nerve stimulation. Epilepsia. 1998;39:998–1000.

    Article  CAS  PubMed  Google Scholar 

  59. Lundgren J, Amark P, Blennow G, Strömblad LG, Wallstedt L. Vagus nerve stimulation in 16 children with refractory epilepsy. Epilepsia. 1998;39:809–13.

    Article  CAS  PubMed  Google Scholar 

  60. Marzec M, Edwards J, Sagher O, Fromes G, Malow BA. Effects of vagus nerve stimulation on sleep-related breathing in epilepsy patients. Epilepsia. 2003;44:930–5.

    Article  PubMed  Google Scholar 

  61. Khurana DS, Reumann M, Hobdell EF, et al. Vagus nerve stimulation in children with refractory epilepsy: unusual complications and relationship to sleep-disordered breathing. Childs Nerv Syst. 2007;23:1309–12.

    Article  PubMed  Google Scholar 

  62. Malow BA, Levy K, Maturen K, Bowes R. Obstructive sleep apnea is common in medically refractory epilepsy patients. Neurology. 2000;55:1002–7.

    Article  CAS  PubMed  Google Scholar 

  63. Malow BA, Edwards J, Marzec M, Sagher O, Fromes G. Effects of vagus nerve stimulation on respiration during sleep: a pilot study. Neurology. 2000;55:1450–4.

    Article  CAS  PubMed  Google Scholar 

  64. Ebben MR, Sethi NK, Conte M, Pollak CP, Labar D. Vagus nerve stimulation, sleep apnea, and CPAP titration. J Clin Sleep Med. 2008;4:471–3.

    PubMed Central  PubMed  Google Scholar 

  65. Oshinsky ML, Murphy AL, Hekierski Jr H, Cooper M, Simon BJ. Noninvasive vagus nerve stimulation as treatment for trigeminal allodynia. Pain. 2014;155(5):1037–42.

    Article  PubMed Central  PubMed  Google Scholar 

  66. Lange G, Janal MN, Maniker A, Fitzgibbons J, Fobler M, Cook D, et al. Safety and efficacy of vagus nerve stimulation in fibromyalgia: a phase I/II proof of concept trial. Pain Med. 2011;12(9):1406–13.

    Article  PubMed Central  PubMed  Google Scholar 

  67. Napadow V, Edwards RR, Cahalan CM, Mensing G, Greenbaum S, Valovska A, et al. Evoked pain analgesia in chronic pelvic pain patients using respiratory-gated auricular vagal afferent nerve stimulation. Pain Med. 2012;13(6):777–89.

    Article  PubMed Central  PubMed  Google Scholar 

  68. Barbanti P, Grazzi L, Egeo G, Padovan AM, Liebler E, Bussone G. Non-invasive vagus nerve stimulation for acute treatment of high-frequency and chronic migraine: an open label study. J Headache Pain. 2015;16:61. doi:10.1186/s10194-015-0542-4.

  69. Straube A, Ellrich J, Eren O, Blum B, Ruscheweyh R. Treatment of chronic migraine with transcutaneous stimulation of the auricular branch of the vagal nerve (auricular t-VNS): a randomized, monocentric clinical trial. J Headache Pain. 2015;16(1):543.

    Article  PubMed  Google Scholar 

  70. Chandler MJ, Zhang J, Qin C, Foreman RD. Spinal inhibitory effects of cardiopulmonary afferent inputs in monkeys: neuronal processing in high cervical segments. J Neurophysiol. 2002;87:1290–302.

    PubMed  Google Scholar 

  71. Zhang J, Chandler MJ, Foreman RD. Thoracic visceral inputs use upper cervical segments to inhibit lumbar spinal neurons in rats. Brain Res. 1996;709:337–42.

    Article  CAS  PubMed  Google Scholar 

  72. Zhang J, Chandler MJ, Foreman RD. Cardio-pulmonary sympathetic and vagal afferents excite C1-C2 propriospinal cells in rats. Brain Res. 2003;969:53–8.

    Article  CAS  PubMed  Google Scholar 

  73. Ammons WS, Blair RWFRD. Vagal afferent inhibition of primate thoracic spinothalamic neurons. J Neurophysiol. 1983;50:926–40.

    CAS  PubMed  Google Scholar 

  74. Ren K, Randich A, Gebhart GF. Spinal serotonergic and kappa opioid receptors mediate facilitation of the tail flick reflex produced by afferent stimulation. Pain. 1991;45:321–9.

    Article  CAS  PubMed  Google Scholar 

  75. Ren K, Randich A, Gebhart GF. Vagal afferent modulation of a nociceptive reflex in rats: involvement of spinal opioid and monoamine receptors. Brain Res. 1988;446:285–94.

    Article  CAS  PubMed  Google Scholar 

  76. Thies R, Foreman RD. Inhibition and excitation of thoracic spinoreticular neurons by electrical stimulation of vagal afferent nerves. Exp Neurol. 1983;82:1–16.

    Article  CAS  PubMed  Google Scholar 

  77. Chandler MJ, Hobbs SF, Bolser DC, Foreman RD. Effects of vagal afferent stimulation on cervical spinothalamic tract neurons in monkeys. Pain. 1991;44:81–7.

    Article  CAS  PubMed  Google Scholar 

  78. Nishikawa Y, Koyama N, Yoshida Y, Yokota T. Activation of ascending antinociceptive system by vagal afferent input as revealed in the nucleus ventralis posteromedialis. Brain Res. 1999;833:108–11.

    Article  CAS  PubMed  Google Scholar 

  79. Randich A, Aicher A. Medullary substrates mediating antinociception produced by electrical stimulation of the vagus. Brain Res. 1988;445:68–76.

    Article  CAS  PubMed  Google Scholar 

  80. Randich A, Ren K, Gebhart GF. Electrical stimulation of cervical vagal afferents. II. Central relays for behavioral antinociception and arterial blood pressure decreases. J Neurophysiol. 1990;64:1115–24.

    CAS  PubMed  Google Scholar 

  81. Ren K, Randcih A, Gebhart GF. Electrical stimulation of cervical vagal afferents. I. Central relays for modulation of spinal nociceptive transmission. J Neurophysiol. 1990;64:1098–114.

    CAS  PubMed  Google Scholar 

  82. Ring HA, White S, Costa DC, Pottinger R, Dick JP, Koeze T, et al. A SPECT study of the effect of vagal nerve stimulation on thalamic activity in patients with epilepsy. Seizure. 2000;9(6):380–4.

    Article  CAS  PubMed  Google Scholar 

  83. Van Laere K, Vonck K, Boon P, Brans B, Vandekerckhove T, Dierckx R. Vagus nerve stimulation in refractory epilepsy: SPECT activation study. J Nucl Med. 2000;41(7):1145–54.

    PubMed  Google Scholar 

  84. Vonck K, Boon P, Van Laere K, D’Havé M, Vandekerckhove T, O’Connor S, et al. Acute single photon emission computed tomographic study of vagus nerve stimulation in refractory epilepsy. Epilepsia. 2000;41(5):601–9.

    Article  CAS  PubMed  Google Scholar 

  85. Meller ST, Lewis SJ, Ness TJ, Brody MJ, Genhart GF. Vagal afferent-mediated inhibition of a nociceptive reflex by intravenous serotonin in the rat. I. Characterization. Brain Res. 1990;524:90–100.

    Article  CAS  PubMed  Google Scholar 

  86. Takeda M, Tanimoto T, Ojima K, Matsumoto S. Suppressive effect of vagal afferents on the activity of the trigeminal spinal neurons related to the jaw-opening reflex in rats: involvement of the endogenous opioid system. Brain Res Bull. 1998;47:49–56.

    Article  CAS  PubMed  Google Scholar 

  87. Ben-Menachem E, Hamberger A, Hedner T, Hammond EJ, Uthman BM, Slater J, et al. Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures. Epilepsy Res. 1995;20:221–7.

    Article  CAS  PubMed  Google Scholar 

  88. Hosoi T, Okuma Y, Nomura Y. Electrical stimulation of afferent vagus nerve induces Il-1 beta expression in the brain and activates HPA axis. Am J Physiol Regul Integr Comp Physiol. 2000;279:R141–7.

    CAS  PubMed  Google Scholar 

  89. Khasar SG, Green PG, Miao FJ, Levine JD. Vagal modulation of nociception is mediated by adrenomedullary epinephrine in the rat. Eur J Neurosci. 2003;17:909–15.

    Article  PubMed  Google Scholar 

  90. Tracey K. Shock Medicine. Sci Am. 2015;312:28–35.

    Article  Google Scholar 

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  1. Department of Anesthesiology and Critical Care Medicine, Division of Pain Medicine, Johns Hopkins School of Medicine, 600 North Wolfe Street, Baltimore, MD, 21287, USA

    Krishnan Chakravarthy, Hira Chaudhry, Kayode Williams & Paul J. Christo

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  1. Krishnan Chakravarthy
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  2. Hira Chaudhry
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  3. Kayode Williams
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Correspondence to Paul J. Christo.

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Krishnan Chakravarthy, Hira Chaudhry, and Paul J. Christo declare that they have no conflict of interest.

Kayode Williams declares a grant from Medtronic Inc. to study Mechanisms of Spinal Cord Stimulation for the treatment of Chronic Pain.

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Chakravarthy, K., Chaudhry, H., Williams, K. et al. Review of the Uses of Vagal Nerve Stimulation in Chronic Pain Management. Curr Pain Headache Rep 19, 54 (2015). https://doi.org/10.1007/s11916-015-0528-6

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