Vagus nerve stimulation

From Wikipedia, the free encyclopedia
Jump to: navigation, search

Vagus nerve stimulation (VNS) is an adjunctive treatment for certain types of intractable epilepsy and treatment-resistant depression.

Vagus nerve action[edit]

Vagus, the tenth cranial nerve, arises from the medulla and carries both afferent and efferent fibers. The afferent vagal fibers connect to the nucleus of the solitary tract which in turn projects connections to other locations in the central nervous system. Little is understood about exactly how vagal nerve stimulation modulates mood and seizure control but proposed mechanisms include alteration of norepinephrine release by projections of solitary tract to the locus coeruleus, elevated levels of inhibitory GABA related to vagal stimulation and inhibition of aberrant cortical activity by reticular activation system.[1]

Approval and endorsement[edit]

In 1997, the United States Food and Drug Administration (FDA) approved the use of VNS as an adjunctive therapy for partial-onset epilepsy. In 2005, the FDA approved the use of VNS for treatment-resistant depression.[2]

Although the use of VNS for refractory depression has been endorsed by the American Psychiatric Association, the FDA's approval of VNS for refractory depression remains controversial. According to Dr. A. John Rush, vice chairman for research in the Department of Psychiatry at the University of Texas Southwestern Medical Center at Dallas, results of the VNS pilot study showed that 40 percent of the treated patients displayed at least a 50 percent or greater improvement in their condition, according to the Hamilton Depression Rating Scale.[3][4] Many other studies concur that VNS is indeed efficacious in treating depression. However, these findings do not take into account improvements over time in patients without the device. In the only randomized controlled trial VNS failed to perform any better when turned on than in otherwise similar implanted patients whose device was not turned on.[5]

Patients[edit]

Charles E. Donovan, a study subject in the investigational trial of vagus nerve stimulation therapy for treatment-resistant depression, wrote Out of the Black Hole: The Patient's Guide to Vagus Nerve Stimulation and Depression.[6]

Other uses[edit]

Because the vagus nerve is associated with many different functions and brain regions, research is being done to determine its usefulness in treating other illnesses, including various anxiety disorders, Alzheimer's disease, migraines,[2] fibromyalgia,[7] obesity,[8] and tinnitus.[9]

  • Alcohol addiction[10]
  • Atrial fibrillation[11][12]
  • Autism[13]
  • Bulimia nervosa[14]
  • Burn-induced organ dysfunction[15]
  • Chronic heart failure[16]
  • Chronic intractable hiccups[17]
  • Comorbid personality disorders[18]
  • Coronary artery disease[19]
  • Dravet syndrome[20]
  • Drop-attacks[21]
  • Heatstroke[22]
  • Inhibits heroin seeking behavior in rats[23]
  • Intestinal epithelial barrier breakdown[24]
  • Lennox-Gastaut syndrome[25]
  • Memory[26]
  • Mood disorders in elderly population[27]
  • Myocarditis[28]
  • Multiple sclerosis[29]
  • Obsessive compulsive disorder[30]
  • Peripheral arterial occlusion disease[31]
  • Postoperative cognitive dysfunction in elderly patients[32]
  • Rasmussen's encephalitis[33]
  • Severe mental diseases[34]
  • Sepsis[35]
  • Spinal trigeminal neuronal[36]
  • Transient focal cerebral ischemia[37]
  • Trauma-hemorrhagic shock[38]
  • Traumatic brain injury[39][40]
  • Vaginal-Cervical self-stimulation in women with complete spinal cord injury[41][42]
  • Visceral pain-related affective memory[43]

Other brain stimulation techniques used to treat depression include Electroconvulsive therapy (ECT) and Cranial electrotherapy stimulation (CES). Deep brain stimulation is currently under study as a treatment for depression. Transcranial magnetic stimulation (TMS) is under study as a therapy for both depression and epilepsy.[44] Trigeminal Nerve Stimulation (TNS) is being researched at UCLA as a treatment for epilepsy.[45]

Adverse effects[edit]

Cardiac[edit]

Cardiac arrhythmia has been reported in lead tests performed during implantation of the device [46][47] along with hundreds upon hundreds of late onset cardiovascular events.[48][49][50][51][52][53]

Sleep apnea[edit]

Intermittent decrease in respiratory flow during sleep has consistently been demonstrated in patients with VNS implants.[54] This seems to be due to an increase in vagal tone,[55] a measure of the control the vagus nerve has over the heartbeat.[56] Clinically significant sleep disordered breathing associated with VNS has been described in pediatric[57] and adult[58] patient populations. Most patients undergoing VNS treatment experience an increase of apnoea hypopnoea index (AHI) post treatment,[58] up to approximately one third develop mild obstructive sleep apnoea post treatment,[58] and a minority of patients develop severe obstructive sleep aponea related to VNS therapy.[57] These obstructive events can be alleviated by decreasing the frequency or intensity of VNS stimulation,[54] by having the patient sleep in non-supine position or by applying positive airway pressure.[58]

Screening for obstructive sleep apnoea (OSA) in patients with a seizure disorder who are undergoing a VNS implant is also important because adequate treatment of previously undiagnosed and untreated OSA is likely to result in better seizure control in these patients.[59]

Patients undergoing vagal nerve stimulator placement are at risk for developing OSA related to the VNS and should therefore be screened clinically for the presence of OSA after the procedure. Continuous Positive Airway Pressure (CPAP) is a viable therapeutic option for patients who develop OSA related to the VNS. Other options include increasing the cycle length or stimulation frequency of the device. With increasing number of indications and the number of patients undergoing the procedure, awareness of this causation is important for appropriate diagnosis and treatment of OSA related to vagal nerve stimulators.[citation needed]

Symptoms such as loud snoring or intermittent cessation of breathing during the night or daytime symptoms as behavioral changes, fatigue and sleepiness may alert the patient or parent to the presence of obstructive sleep apnoea, but these symptoms are generally insensitive and a sleep study (diagnostic polysomnography) is generally required to diagnose the presence of obstructive sleep apnoea. The fact that many of these patients are children and may have associated cognitive deficits makes diagnosing the problem even more difficult without a sleep study.[citation needed]

Other[edit]

VNS causes stimulation of the superior and recurrent laryngeal nerves and is associated with problems ranging from alteration of voice(66%), coughing(45%), pharyngitis(35%) and throat pain(28%)[57] and hoarseness (very common) to frank laryngeal muscle spasm and upper airway obstruction (rare).[60] "Increased muscle tension," presumably in the upper body, may be experienced during the stimulation period.[61] The left vagus has proportionally lesser number of cardiac efferent fibers and placing the stimulator on this side potentially limits the arrhythmogenic effects of vagal stimulation but reversible bradyarrhythmias associated with vagal nerve stimulators have been well described.[62] Other nonspecific symptoms include headache, nausea, vomiting, dyspepsia,[62] dyspnea and paresthesia.[44]

In the treatment of epilepsy, randomized control trials conducted in the United States indicated that one-third of the patients using a particular vagus nerve stimulation device had some type of an increase in seizures, with 17 percent having greater than a 25 percent increase. In each of the studies, there were patients who had greater than a 100 percent increase. In the E05 study, the range went up to a 234 percent increase, while in the E04 study, it went even higher, to a 680 percent maximum range.[63][64]

Anti-inflammatory activities of vagus nerve stimulation[edit]

The discovery by Kevin J. Tracey that vagus nerve stimulation inhibits inflammation by suppressing pro-inflammatory cytokine production has led to significant interest in the potential to use this approach for treating inflammatory diseases ranging from arthritis to colitis, ischemia, myocardial infarction, and congestive heart failure.[65] Action potentials transmitted in the vagus nerve activate the efferent arm of the Inflammatory Reflex, the neural circuit that converges on the spleen to inhibit the production of TNF and other pro-inflammatory cytokines by macrophages there.[66] This efferent arc is also known as the Cholinergic anti-inflammatory pathway[67] Because this strategy targets the release of TNF and other pro-inflammatory cytokines, it may be possible to use vagus nerve stimulation instead of anti-inflammatory antibodies (e.g., Remicade or Enbrel) to treat inflammation.

A recent study published in Science (Sept 15, 2011 DOI : 10.1126/science.1209985) demonstrated the existence of acetylcholine-synthesizing T-cells in the spleen that respond to vagal stimulation, resulting in suppression of inflammatory response / TNF-alpha via macrophages.

Methods of stimulation[edit]

Direct vagus nerve stimulation[edit]

This is currently the only widely used method of therapeutic VNS. It requires the surgical implantation of a stimulator device.

The Cyberonics VNS devices consist of a titanium-encased generator about the size of a pocket watch with a lithium battery to fuel the generator, a lead wire system with electrodes, and an anchor tether to secure leads to the vagus nerve. The battery life for the pulse generator is "between 1 [and] 16 years, depending on the settings [ie how strong the signal being sent is, the length of time the device stimulates the nerve each time, and how frequently the device stimulates the nerve]."[68]

Implantation of the Cyberonics VNS device is usually done as an out-patient procedure. The procedure goes as follows: an incision is made in the upper left chest and the generator is implanted into a little "pouch" on the left chest under the clavicle. A second incision is made in the neck, so that the surgeon can access the vagus nerve. The surgeon then wraps the leads around the left branch of the vagus nerve, and connects the electrodes to the generator. Once successfully implanted, the generator sends electric impulses to the vagus nerve at regular intervals.[69] The left vagus nerve is stimulated rather than the right because the right plays a role in cardiac function such that stimulating it could have negative cardiac effects.[44]

The device is currently only made by Cyberonics, Inc. However, other "wearable" devices are being tested and developed by other companies that involve transcutaneous stimulation and do not require surgery. These devices are similar to TENS (Transcutaneous Electrical Nerve Stimulation) devices that are often used for pain management.[citation needed]

Transcutaneous vagus nerve stimulation (t-VNS)[edit]

This method allows for the stimulation of the vagus nerve without surgical procedure. Electrical impulses are targeted at the aurical (ear), at points where branches of the vagus nerve have cutaneous representation. Specifically the concha has been target for t-VNS.[citation needed]

See also[edit]

References[edit]

  1. ^ Ghanem, T; Early, S (2006). "Vagal nerve stimulator implantation: An otolaryngologist's perspective". Otolaryngology - Head and Neck Surgery 135 (1): 46–51. doi:10.1016/j.otohns.2006.02.037. PMID 16815181. 
  2. ^ a b Groves, Duncan A.; Brown, Verity J. (2005). "Vagal nerve stimulation: A review of its applications and potential mechanisms that mediate its clinical effects". Neuroscience & Biobehavioral Reviews 29 (3): 493. doi:10.1016/j.neubiorev.2005.01.004. 
  3. ^ Doctor's Guide: Vagus Nerve Stimulation Successful For Depression
  4. ^ Neurology Channel: Vagus Nerve Stimulation[dead link]
  5. ^ FDA Summary of VNS Data
  6. ^ Donovan, Charles E. (2006). Out of the Black Hole: A Patient's Guide to Vagus Nerve Stimulation and Depression. Wellness Publishers. ISBN 978-0-9748484-3-3. [non-primary source needed]
  7. ^ ClinicalTrials.gov NCT00294281 Vagus Nerve Stimulation for Treating Adults With Severe Fibromyalgia
  8. ^ Karason K, Mølgaard H, Wikstrand J, Sjöström L (April 1999). "Heart rate variability in obesity and the effect of weight loss". The American Journal of Cardiology 83 (8): 1242–7. doi:10.1016/S0002-9149(99)00066-1. PMID 10215292. 
  9. ^ http://www.utdallas.edu/news/2010/8/9-4791_NIH-Grant-Supports-Profs-Search-for-Tinnitus-Cure_article.html[full citation needed]
  10. ^ Herremans SC, Baeken C (September 2012). "The current perspective of neuromodulation techniques in the treatment of alcohol addiction: a systematic review". Psychiatria Danubina 24 (Suppl 1): S14–20. PMID 22945180. 
  11. ^ Shen MJ, Shinohara T, Park HW, et al. (May 2011). "Continuous low-level vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines". Circulation 123 (20): 2204–12. doi:10.1161/CIRCULATIONAHA.111.018028. PMC 3101282. PMID 21555706. 
  12. ^ Sha Y, Scherlag BJ, Yu L, et al. (October 2011). "Low-level right vagal stimulation: anticholinergic and antiadrenergic effects". Journal of Cardiovascular Electrophysiology 22 (10): 1147–53. doi:10.1111/j.1540-8167.2011.02070.x. PMID 21489033. 
  13. ^ Levy ML, Levy KM, Hoff D, et al. (June 2010). "Vagus nerve stimulation therapy in patients with autism spectrum disorder and intractable epilepsy: results from the vagus nerve stimulation therapy patient outcome registry". Journal of Neurosurgery. Pediatrics 5 (6): 595–602. doi:10.3171/2010.3.PEDS09153. PMID 20515333. 
  14. ^ Faris PL, Eckert ED, Kim SW, et al. (May 2006). "Evidence for a vagal pathophysiology for bulimia nervosa and the accompanying depressive symptoms". Journal of Affective Disorders 92 (1): 79–90. doi:10.1016/j.jad.2005.12.047. PMID 16516303. 
  15. ^ Niederbichler AD, Papst S, Claassen L, et al. (September 2009). "Burn-induced organ dysfunction: vagus nerve stimulation attenuates organ and serum cytokine levels". Burns 35 (6): 783–9. doi:10.1016/j.burns.2008.08.023. PMID 19482432. 
  16. ^ Abraham WT, Smith SA (February 2013). "Devices in the management of advanced, chronic heart failure". Nature Reviews. Cardiology 10 (2): 98–110. doi:10.1038/nrcardio.2012.178. PMC 3753073. PMID 23229137. 
  17. ^ Payne BR, Tiel RL, Payne MS, Fisch B (May 2005). "Vagus nerve stimulation for chronic intractable hiccups. Case report". Journal of Neurosurgery 102 (5): 935–7. doi:10.3171/jns.2005.102.5.0935. PMID 15926725. 
  18. ^ http://clinicaltrialsfeeds.org/clinical-trials/show/NCT01119053[full citation needed]
  19. ^ http://academic.research.microsoft.com/Publication/35509092/vagal-neurostimulation-in-patients-with-coronary-artery-disease[full citation needed]
  20. ^ Spatola M, Jeannet PY, Pollo C, Wider C, Labrum R, Rossetti AO (2013). "Effect of vagus nerve stimulation in an adult patient with Dravet syndrome: contribution to sudden unexpected death in epilepsy risk reduction?". European Neurology 69 (2): 119–21. doi:10.1159/000345132. PMID 23207687. 
  21. ^ Zamponi N, Passamonti C, Cesaroni E, Trignani R, Rychlicki F (July 2011). "Effectiveness of vagal nerve stimulation (VNS) in patients with drop-attacks and different epileptic syndromes". Seizure 20 (6): 468–74. doi:10.1016/j.seizure.2011.02.011. PMID 21396833. 
  22. ^ Yamakawa K, Matsumoto N, Imamura Y, et al. (2013). "Electrical vagus nerve stimulation attenuates systemic inflammation and improves survival in a rat heatstroke model". Plos One 8 (2): e56728. doi:10.1371/journal.pone.0056728. PMC 3570456. PMID 23424673. 
  23. ^ Liu H, Liu Y, Yu J, et al. (April 2011). "Vagus nerve stimulation inhibits heroin-seeking behavior induced by heroin priming or heroin-associated cues in rats". Neuroscience Letters 494 (1): 70–4. doi:10.1016/j.neulet.2011.02.059. PMID 21362452. 
  24. ^ Krzyzaniak M, Peterson C, Loomis W, et al. (May 2011). "Postinjury vagal nerve stimulation protects against intestinal epithelial barrier breakdown". The Journal of Trauma 70 (5): 1168–75; discussion 1175–6. doi:10.1097/TA.0b013e318216f754. PMID 21610431. 
  25. ^ http://livingwithlgs.com/vagus-nerve-stimulation.aspx[full citation needed]
  26. ^ Ghacibeh GA, Shenker JI, Shenal B, Uthman BM, Heilman KM (September 2006). "The influence of vagus nerve stimulation on memory". Cognitive and Behavioral Neurology 19 (3): 119–22. doi:10.1097/01.wnn.0000213908.34278.7d. PMID 16957488. 
  27. ^ Rosenberg O, Shoenfeld N, Kotler M, Dannon PN (June 2009). "Mood disorders in elderly population: neurostimulative treatment possibilities". Recent Patents on CNS Drug Discovery 4 (2): 149–59. PMID 19519563. 
  28. ^ Li H, Yang TD (November 2009). "Vagus nerve stimulation may be used in the therapy of myocarditis". Medical Hypotheses 73 (5): 725–7. doi:10.1016/j.mehy.2009.04.036. PMID 19481875. 
  29. ^ Polak T, Zeller D, Fallgatter AJ, Metzger FG (March 2013). "Vagus somatosensory-evoked potentials are prolonged in patients with multiple sclerosis with brainstem involvement". Neuroreport 24 (5): 251–3. doi:10.1097/WNR.0b013e32835f00a3. PMID 23407276. 
  30. ^ http://www.ocdcentral.info/tag/vagus-nerve-stimulation[full citation needed]
  31. ^ Payrits T, Ernst A, Ladits E, Pokorny H, Viragos I, Längle F (October 2011). "Vagale Stimulation–eine neue Möglichkeit zur konservativen Therapie der peripheren arteriellen Verschlusskrankheit" [Vagal stimulation - a new possibility for conservative treatment of peripheral arterial occlusion disease]. Zentralblatt Für Chirurgie (in German) 136 (5): 431–5. doi:10.1055/s-0031-1283739. PMID 22009541. 
  32. ^ Xiong J, Xue FS, Liu JH, et al. (December 2009). "Transcutaneous vagus nerve stimulation may attenuate postoperative cognitive dysfunction in elderly patients". Medical Hypotheses 73 (6): 938–41. doi:10.1016/j.mehy.2009.06.033. PMID 19631475. 
  33. ^ Grujic J, Bien CG, Pollo C, Rossetti AO (January 2011). "Vagus nerve stimulator treatment in adult-onset Rasmussen's encephalitis". Epilepsy & Behavior 20 (1): 123–5. doi:10.1016/j.yebeh.2010.10.024. PMID 21130042. 
  34. ^ Steinberg H (July 2013). "A pioneer work on electric brain stimulation in psychotic patients. Rudolph Gottfried Arndt and his 1870s studies". Brain Stimulation 6 (4): 477–81. doi:10.1016/j.brs.2012.11.004. PMID 23266132. 
  35. ^ Kumar V, Sharma A (January 2010). "Is neuroimmunomodulation a future therapeutic approach for sepsis?". International Immunopharmacology 10 (1): 9–17. doi:10.1016/j.intimp.2009.10.003. PMID 19840870. 
  36. ^ Lyubashina OA, Sokolov AY, Panteleev SS (October 2012). "Vagal afferent modulation of spinal trigeminal neuronal responses to dural electrical stimulation in rats". Neuroscience 222: 29–37. doi:10.1016/j.neuroscience.2012.07.011. PMID 22800563. 
  37. ^ Hiraki T, Baker W, Greenberg JH (April 2012). "Effect of vagus nerve stimulation during transient focal cerebral ischemia on chronic outcome in rats". Journal of Neuroscience Research 90 (4): 887–94. PMC 3306061. PMID 22420043. 
  38. ^ Levy G, Fishman JE, Xu D, et al. (January 2013). "Parasympathetic stimulation via the vagus nerve prevents systemic organ dysfunction by abrogating gut injury and lymph toxicity in trauma and hemorrhagic shock". Shock 39 (1): 39–44. doi:10.1097/SHK.0b013e31827b450. PMC 3547655. PMID 23247120. 
  39. ^ Lopez NE, Krzyzaniak MJ, Costantini TW, et al. (June 2012). "Vagal nerve stimulation decreases blood-brain barrier disruption after traumatic brain injury". The Journal of Trauma and Acute Care Surgery 72 (6): 1562–6. doi:10.1097/TA.0b013e3182569875. PMID 22695423. 
  40. ^ Kumaria A, Tolias CM (June 2012). "Is there a role for vagus nerve stimulation therapy as a treatment of traumatic brain injury?". British Journal of Neurosurgery 26 (3): 316–20. doi:10.3109/02688697.2012.663517. PMID 22404761. 
  41. ^ Komisaruk BR, Whipple B, Crawford A, Liu WC, Kalnin A, Mosier K (October 2004). "Brain activation during vaginocervical self-stimulation and orgasm in women with complete spinal cord injury: fMRI evidence of mediation by the vagus nerves". Brain Research 1024 (1-2): 77–88. doi:10.1016/j.brainres.2004.07.029. PMID 15451368. 
  42. ^ Whipple B, Komisaruk BR (2002). "Brain (PET) responses to vaginal-cervical self-stimulation in women with complete spinal cord injury: preliminary findings". Journal of Sex & Marital Therapy 28 (1): 79–86. doi:10.1080/009262302317251043. PMID 11928182. 
  43. ^ Zhang X, Cao B, Yan N, et al. (January 2013). "Vagus nerve stimulation modulates visceral pain-related affective memory". Behavioural Brain Research 236 (1): 8–15. doi:10.1016/j.bbr.2012.08.027. PMID 22940455. 
  44. ^ a b c George, M; Sackeim, HA; Rush, AJ; Marangell, LB; Nahas, Z; Husain, MM; Lisanby, S; Burt, T et al. (2000). "Vagus nerve stimulation: A new tool for brain research and therapy*". Biological Psychiatry 47 (4): 287–95. doi:10.1016/S0006-3223(99)00308-X. PMID 10686263. 
  45. ^ "UCLA Develops Unique Nerve-stimulation Epilepsy Treatment; "Brain Pacemaker" Designed as External or Implant Device" (Press release). 2006-07-25. Retrieved 2006-07-26. 
  46. ^ http://www.vnsmessageboard.com/index.php/topic,4476.0.html[self-published source?]
  47. ^ http://www.vnsmessageboard.com/index.php/topic,3842.0.html[self-published source?]
  48. ^ http://www.vnsmessageboard.com/index.php/topic,3850.0.html[self-published source?]
  49. ^ http://www.vnsmessageboard.com/index.php/topic,4008.0.html[self-published source?]
  50. ^ http://www.vnsmessageboard.com/index.php/topic,4011.0.html[self-published source?]
  51. ^ http://www.vnsmessageboard.com/index.php/topic,3832.0.html[self-published source?]
  52. ^ http://www.vnsmessageboard.com/index.php/topic,3862.0.html[self-published source?]
  53. ^ http://www.vnsmessageboard.com/index.php/topic,3868.0.html[self-published source?]
  54. ^ a b Malow, BA; Edwards, J; Marzec, M; Sagher, O; Fromes, G (2000). "Effects of vagus nerve stimulation on respiration during sleep: A pilot study". Neurology 55 (10): 1450–4. doi:10.1212/wnl.55.10.1450. PMID 11094096. 
  55. ^ Marzec, Mary; Edwards, Jonathan; Sagher, Oren; Fromes, Gail; Malow, Beth A. (2003). "Effects of Vagus Nerve Stimulation on Sleep-related Breathing in Epilepsy Patients". Epilepsia 44 (7): 930–5. doi:10.1046/j.1528-1157.2003.56202.x. PMID 12823576. 
  56. ^ "HP-5A: Heart Rate and Blood Pressure". iWorx Systems Inc. Retrieved 12 May 2014. 
  57. ^ a b c Hsieh, T; Chen, M; McAfee, A; Kifle, Y (2008). "Sleep-Related Breathing Disorder in Children with Vagal Nerve Stimulators". Pediatric Neurology 38 (2): 99–103. doi:10.1016/j.pediatrneurol.2007.09.014. PMID 18206790. 
  58. ^ a b c d Marzec, Mary; Edwards, Jonathan; Sagher, Oren; Fromes, Gail; Malow, Beth A. (2003). "Effects of Vagus Nerve Stimulation on Sleep-related Breathing in Epilepsy Patients". Epilepsia 44 (7): 930–5. doi:10.1046/j.1528-1157.2003.56202.x. PMID 12823576. 
  59. ^ Vaughn, B; Dcruz, O; Beach, R; Messenheimer, J (1996). "Improvement of epileptic seizure control with treatment of obstructive sleep apneoa". Seizure 5 (1): 73–8. doi:10.1016/S1059-1311(96)80066-5. PMID 8777557. 
  60. ^ Bernards, Christopher M. (2004). "An Unusual Cause of Airway Obstruction during General Anesthesia with a Laryngeal Mask Airway". Anesthesiology 100 (4): 1017–8. doi:10.1097/00000542-200404000-00037. PMID 15087642. 
  61. ^ "Vagus Nerve Stimulation". University of Michigan Depression Center. Retrieved 28 August 2013. 
  62. ^ a b Hatton, Kevin W.; McLarney, J Thomas; Pittman, Thomas; Fahy, Brenda G. (2006). "Vagal Nerve Stimulation: Overview and Implications for Anesthesiologists". Anesthesia & Analgesia 103 (5): 1241–9. doi:10.1213/01.ane.0000244532.71743.c6. 
  63. ^ pg. 125 http://www.fda.gov/ohrms/dockets/AC/97/transcpt/3299t1.pdf
  64. ^ http://www.vnsmessageboard.com/index.php/topic,4117.0.html[self-published source?]
  65. ^ Tracey, Kevin J. (2007). "Physiology and immunology of the cholinergic antiinflammatory pathway". Journal of Clinical Investigation 117 (2): 289–96. doi:10.1172/JCI30555. PMC 1783813. PMID 17273548. 
  66. ^ Rosas-Ballina, M.; Ochani, M.; Parrish, W. R.; Ochani, K.; Harris, Y. T.; Huston, J. M.; Chavan, S.; Tracey, K. J. (2008). "Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia". Proceedings of the National Academy of Sciences 105 (31): 11008–13. doi:10.1073/pnas.0803237105. PMC 2504833. PMID 18669662. 
  67. ^ Tracey, Kevin J. (2009). "Reflex control of immunity". Nature Reviews Immunology 9 (6): 418–28. doi:10.1038/nri2566. PMID 19461672. 
  68. ^ Cyberonics, Inc. (2007.) VNS Therapy Patient Essentials: Depression.
  69. ^ Panescu, Dorin (2005). Emerging Technologies: Vagus Nerve Stimulation for the Treatment of Depression. IEEE Engineering in Medicine and Biology Magazine.[page needed]

Further reading[edit]

  • Medical Devices That Can Kill

http://www.newamerica.net/node/35911

  • Report casts doubt on VNS approval

http://www.thefreelibrary.com/Report+casts+doubt+on+VNS+approval.-a0149222466

  • Vagal inhibition

http://healthdrip.com/vagal-inhibition/

External links[edit]