Single-pulse activation of the cholinergic anti-inflammatory pathway to treat chronic inflammation
Described herein are methods and systems for applying extremely low duty-cycle stimulation sufficient to treat chronic inflammation. In particular, described herein are single supra-threshold pulses of electrical stimulation sufficient to result in a long-lasting (e.g., >4 hours, greater than 12 hours, greater than 24 hours, greater than 48 hours) inhibition of pro-inflammatory cytokines and/or effects of chronic inflammation. These methods and devices are particularly of interest in treatment of inflammatory bowel disease (IBD).
1. A system for treating chronic inflammation in a patient, the system comprising:
an implantable microstimulator configured to apply a low duty-cycle stimulation to a vagus nerve, wherein the low duty-cycle stimulation provides no more than a single supra-threshold pulse every four hours; and
a controller configured to set a dose for the microstimulator wherein the dose comprises the single supra-threshold pulse followed by an off-period of at least four hours, wherein the single supra-threshold pulse is configured to reduce a level of inflammation in the patient.
2. The system of claim 1 , wherein the off-period is at least 24 hours.
3. The system of claim 1 , wherein the off-period is at least 48 hours.
4. The system of claim 1 , wherein the single supra-threshold pulse has a pulse amplitude of less than 5 mA.
5. The system of claim 1 , wherein the single supra-threshold pulse has a pulse amplitude of less than 3 mA.
6. The system of claim 1 , wherein the single supra-threshold pulse has a pulse amplitude of less than 2 mA.
7. The system of claim 1 , wherein the single supra-threshold pulse is biphasic.
8. The system of claim 1 , wherein the chronic inflammation is intestinal inflammation.
9. The system of claim 1 , wherein the chronic inflammation is inflammatory bowel disease.
10. The system of claim 1 , wherein the chronic inflammation is Crohn's disease.
11. A method of treating chronic inflammation in a patient, the method comprising:
implanting a microstimulator; and
applying only a single supra-threshold stimulus pulse from the microstimulator to the vagus nerve followed by an off-time of at least 4 hours; and
reducing a level of inflammation in the patient.
12. The method of claim 11 , wherein the off-time is at least 24 hours.
13. The method of claim 11 , wherein the off-time is at least 48 hours.
14. The method of claim 11 , wherein the single supra-threshold stimulus pulse has a pulse amplitude of less than 5 mA.
15. The method of claim 11 , wherein the single supra-threshold stimulus pulse has a pulse amplitude of less than 3 mA.
16. The method of claim 11 , wherein the single supra-threshold stimulus pulse has a pulse amplitude of less than 2 mA.
17. The method of claim 11 , wherein the single supra-threshold stimulus pulse is biphasic.
18. The method of claim 11 , wherein the chronic inflammation is intestinal inflammation.
19. The method of claim 11 , wherein the chronic inflammation is inflammatory bowel disease.
20. The method of claim 11 , wherein the chronic inflammation is Crohn's disease.