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

Overview

Journal Curr Pain Headache Rep

Date 2015 Oct 24

PMID 26493698

Citations 59

Authors

Krishnan Chakravarthy

Hira Chaudhry

Kayode Williams

Paul J Christo

Affiliations

Soon will be listed here.

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.

Citing Articles

Pain and the autonomic nervous system. The role of non-invasive neuromodulation with NESA microcurrents.

Azevedo N, Medina-Ramirez R Front Pain Res (Lausanne). 2025; 6:1410808.

PMID: 40034400 PMC: 11873094. DOI: 10.3389/fpain.2025.1410808.

Transcutaneous vagus nerve stimulation as a pain modulator in knee osteoarthritis: a randomized controlled clinical trial.

Elsehrawy G, Ibrahim M, A Moneim N, Hefny M, El Shaarawy N BMC Musculoskelet Disord. 2025; 26(1):68.

PMID: 39828740 PMC: 11744843. DOI: 10.1186/s12891-025-08288-6.

Advances in VNS efficiency and mechanisms of action on cognitive functions.

Wang W, Li R, Li C, Liang Q, Gao X Front Physiol. 2024; 15:1452490.

PMID: 39444752 PMC: 11496278. DOI: 10.3389/fphys.2024.1452490.

Transcutaneous vagus nerve stimulation effects on chronic pain: systematic review and meta-analysis.

Costa V, Gianlorenco A, Andrade M, Camargo L, Menacho M, Avila M Pain Rep. 2024; 9(5):e1171.

PMID: 39131814 PMC: 11309651. DOI: 10.1097/PR9.0000000000001171.

Using neural biomarkers to personalize dosing of vagus nerve stimulation.

Berthon A, Wernisch L, Stoukidi M, Thornton M, Tessier-Lariviere O, Fortier-Poisson P Bioelectron Med. 2024; 10(1):15.

PMID: 38880906 PMC: 11181600. DOI: 10.1186/s42234-024-00147-4.

References

Randich A, Ren K, Gebhart G . Electrical stimulation of cervical vagal afferents. II. Central relays for behavioral antinociception and arterial blood pressure decreases. J Neurophysiol. 1990; 64(4):1115-24. DOI: 10.1152/jn.1990.64.4.1115. View

Ammons W, Blair R, Foreman R . Vagal afferent inhibition of primate thoracic spinothalamic neurons. J Neurophysiol. 1983; 50(4):926-40. DOI: 10.1152/jn.1983.50.4.926. View

Ben-Menachem E . Vagus-nerve stimulation for the treatment of epilepsy. Lancet Neurol. 2003; 1(8):477-82. DOI: 10.1016/s1474-4422(02)00220-x. View

Randich A, Gebhart G . Vagal afferent modulation of nociception. Brain Res Brain Res Rev. 1992; 17(2):77-99. DOI: 10.1016/0165-0173(92)90009-b. View

Cechetto D . Central representation of visceral function. Fed Proc. 1987; 46(1):17-23. View

Ben-Menachem E, Hamberger A, Hedner T, Hammond E, Uthman B, Slater J . Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures. Epilepsy Res. 1995; 20(3):221-7. DOI: 10.1016/0920-1211(94)00083-9. View

Mauskop A . Vagus nerve stimulation relieves chronic refractory migraine and cluster headaches. Cephalalgia. 2005; 25(2):82-6. DOI: 10.1111/j.1468-2982.2005.00611.x. View

Meller S, Lewis S, Ness T, BRODY M, Gebhart G . Vagal afferent-mediated inhibition of a nociceptive reflex by intravenous serotonin in the rat. I. Characterization. Brain Res. 1990; 524(1):90-100. DOI: 10.1016/0006-8993(90)90496-x. View

Ren K, Randich A, Gebhart G . Vagal afferent modulation of a nociceptive reflex in rats: involvement of spinal opioid and monoamine receptors. Brain Res. 1988; 446(2):285-94. DOI: 10.1016/0006-8993(88)90887-6. View

10.

Thies R, Foreman R . Inhibition and excitation of thoracic spinoreticular neurons by electrical stimulation of vagal afferent nerves. Exp Neurol. 1983; 82(1):1-16. DOI: 10.1016/0014-4886(83)90238-8. View

11.

Ben-Menachem E, Revesz D, Simon B, Silberstein S . Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Eur J Neurol. 2015; 22(9):1260-8. PMC: 5024045. DOI: 10.1111/ene.12629. View

12.

Ring H, White S, Costa D, POTTINGER R, Dick J, Koeze T . A SPECT study of the effect of vagal nerve stimulation on thalamic activity in patients with epilepsy. Seizure. 2000; 9(6):380-4. DOI: 10.1053/seiz.2000.0438. View

13.

Ren K, Randich A, Gebhart G . Spinal serotonergic and kappa opioid receptors mediate facilitation of the tail flick reflex produced by vagal afferent stimulation. Pain. 1991; 45(3):321-329. DOI: 10.1016/0304-3959(91)90057-5. View

14.

Ebben M, Sethi N, Conte M, Pollak C, Labar D . Vagus nerve stimulation, sleep apnea, and CPAP titration. J Clin Sleep Med. 2008; 4(5):471-3. PMC: 2576315. View

15.

Lundgren J, Amark P, Blennow G, Stromblad L, Wallstedt L . Vagus nerve stimulation in 16 children with refractory epilepsy. Epilepsia. 1998; 39(8):809-13. DOI: 10.1111/j.1528-1157.1998.tb01173.x. View

16.

Sadler R, Purdy R, Rahey S . Vagal nerve stimulation aborts migraine in patient with intractable epilepsy. Cephalalgia. 2002; 22(6):482-4. DOI: 10.1046/j.1468-2982.2002.00387.x. View

17.

Amark P, Stodberg T, Wallstedt L . Late onset bradyarrhythmia during vagus nerve stimulation. Epilepsia. 2007; 48(5):1023-4. DOI: 10.1111/j.1528-1167.2007.01023.x. View

18.

Schuurman P, Beukers R . Ventricular asystole during vagal nerve stimulation. Epilepsia. 2009; 50(4):967-8. DOI: 10.1111/j.1528-1167.2008.01907.x. View

19.

Ali I, Pirzada N, Kanjwal Y, Wannamaker B, Medhkour A, Koltz M . Complete heart block with ventricular asystole during left vagus nerve stimulation for epilepsy. Epilepsy Behav. 2004; 5(5):768-71. DOI: 10.1016/j.yebeh.2004.05.008. View

20.

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; 16:543. PMC: 4496420. DOI: 10.1186/s10194-015-0543-3. View