Vagal nerve stimulation has anti inflammatory benefits - the future treatments for Psa?

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Anti-inflammatory activities of vagus nerve stimulation

The discovery by Kevin J. Tracey that vagus nerve stimulation inhibits inflammation by suppressing 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 infaction, and congestive heart failure.[20] 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 cytokines by macrophages there.[21] This efferent arc is also known as the Cholinergic anti-inflammatory pathway[22] Because this strategy targets the release of TNF, it may be possible to use vagus nerve stimulation instead of anti-TNF antibodies (e.g., Remicade or Enbrel) to treat inflammation. SetPoint Medical, Inc. is an early-stage medical device company developing the experimental implantable neurostimulation devices for the treatment of inflammation.[23]

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.

[edit] Methods of Stimulation

[edit] Vagal Maneuvers

VNS can be achieved by one of the Vagal maneuvers, though these are not suitable for therapeutic use.

[edit] Direct Vagus Nerve Stimulation

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]."[24]

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.[25] 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.[10]

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]

[edit] Transcutaneous Vagus Nerve Stimulation (t-VNS)

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]

One such t-VNS device is cerbomed's NEMOS.[26] It is just coming onto the market in 2012. To date, there have been conducted several pilot studies on the effectiveness of t-VNS in different indications:[27][28] Epilepsy: A case series with seven patients who suffer from drug-resistant epilepsy has been conducted. The patients have been treated with t-VNS for nine months. The results indicate the potential for seizure reduction of t-VNS in drug-resistant epilepsies.[29] Pain: Results of a randomized, controlled study investigating somatosensory pain processing with 48 healthy volunteers showed a statistically significant and thus potentially clinically relevant lowering of the mechanical pain perception and a rise in the pressure pain threshold in subjects receiving t-VNS.[30] Several patents have already been filed. US Patent Application Publication Nos. #20070067004, #20080249594, #20090287035, #20100057154.

[edit] See also

[edit] References

  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.