Extremely low duty-cycle activation of the cholinergic anti-inflammatory pathway to treat chronic inflammation
Described herein are systems and methods for applying extremely low duty-cycle stimulation sufficient to treat chronic inflammation using feedback to adjust the off times between stimulations. In particular, the feedback include an assessment of the level of inflammation by the patient or the healthcare provider, or by measure the level of an inflammatory analyte or biomarker, or by detecting nerve activity correlated with inflammation.
1. A system for treating chronic inflammation in a subject, the system comprising:
an implantable microstimulator configured to apply a low duty-cycle dose regimen to a vagus nerve; and
a controller adapted to set the low duty-cycle dose regimen, wherein the low duty-cycle dose regimen comprises a plurality of electrical stimulations to the vagus nerve that are separated by an adjustable off period of at least 4 hours that is determined at least in part on feedback received by the controller, wherein each electrical stimulation comprises one supra-threshold pulse or burst.
2. The system of claim 1 , wherein the feedback is an indicator of a level of inflammation.
3. The system of claim 1 , wherein the feedback is the subject's assessment of a level of inflammation based on a determination of swelling and/or pain.
4. The system of claim 1 , wherein the feedback is a health care provider's assessment of a level of inflammation based on a determination of swelling and/or pain.
5. The system of claim 1 , wherein the feedback is a measurement of a level of an inflammatory analyte or biomarker in the subject's blood or bodily fluids.
6. The system of claim 1 , further comprising a sensing electrode configured to monitor nerve activity, the sensing electrode in communication with the controller, wherein the feedback comprises nerve activity detected by the sensing electrode.
7. The system of claim 6 , wherein the sensing electrode is a part of the microstimulator.
8. The system of claim 6 , wherein the sensing electrode is configured to monitor vagus nerve activity.
9. The system of claim 1 , wherein the electrical stimulations comprise an adjustable amplitude that is determined at least in part on feedback received by the controller.
10. A method of treating chronic inflammation in a subject, the method comprising:
applying a plurality of electrical stimulations to a vagus nerve using a microstimulator, wherein the electrical stimulations are separated by an adjustable off period of at least 4 hours;
determining a level of inflammation suffered by the subject; and
adjusting the adjustable off period between electrical stimulations based at least in part on the determined level of inflammation, wherein each electrical stimulation comprises one supra-threshold pulse or burst.
11. The method of claim 10 , wherein the step of determining the level of inflammation comprises monitoring nerve activity.
12. The method of claim 11 , wherein the nerve activity is vagus nerve activity.
13. The method of claim 10 , wherein the step of determining the level of inflammation comprises measuring the swelling and/or pain experienced by the subject.
14. The method of claim 10 , wherein the step of determining the level of inflammation comprises measuring a level of inflammatory analyte or biomarker in the subject's blood or bodily fluid.
15. The method of claim 10 , wherein the step of determining the level of inflammation is performed at predetermined intervals.
16. The method of claim 10 , further comprising adjusting an amplitude of the electrical stimulations based at least in part on the determined level of inflammation.