Treating inflammatory disorders by electrical vagus nerve stimulation

• US 20060178703A1
• Filed: 12/22/2005
• Published: 08/10/2006
• Est. Priority Date: 12/27/2004
• Status: Active Grant

• Current Assignee: The Feinstein Institutes For Medical Research
• Original Assignee: The Feinstein Institutes For Medical Research
• Inventors: Tracey, Kevin J., Huston, Jared M.
• Granted Patent: US 11,344,724 B2
• Time in Patent Office: Days
• US Class Current: 607/2
• CPC Class Codes: A61N 1/36053 adapted for vagal stimulation A61N1/36114 takes precedence
• CPC Class Codes: A61N 1/36114 Cardiac control, e.g. by vagal stimulation stimulating the heart A61N1/362

Abstract

A method and an apparatus for treating a patient suffering from, or at risk for, a condition mediated by the inflammatory cytokine cascade, by electrically stimulating vagus nerve activity in an amount sufficient to inhibit the inflammatory cytokine cascade.

Claims

1. A method for treating a subject suffering from, or at risk for, an inflammatory disorder, comprising stimulating the vagus nerve in a subject with an electrical signal, wherein the signal voltage is from 0.01 Volt to 1 Volt, provided that the condition is not ileus, asthma or cystic fibrosis.

2. The method of claim 1 wherein the signal voltage is from 0.01 Volt to 0.05 Volt.

3. The method of claim 1 wherein pulse width is from 0.1 ms to 5 ms;

signal frequency is from 0.1 Hz to 30 Hz; and

signal on-time is from 1 second to 120 seconds.

4. The method of claim 1 wherein signal voltage is from 0.01 Volt to 0.05 Volt;

pulse width is from 0.1 ms to 0.5 ms;

signal frequency is from 10 Hz to 30 Hz; and

signal on-time is from 20 seconds to 40 seconds.

5. The method of claim 1 wherein the inflammatory disorder is selected from the group consisting of appendicitis, peptic ulcer, gastric ulcer, duodenal ulcer, peritonitis, pancreatitis, ulcerative colitis, pseudomembranous colitis, acute colitis, ischemic colitis, diverticulitis, epiglottitis, achalasia, cholangitis, cholecystitits, hepatitis, Crohn'"'"'s disease, enteritis, Whipple'"'"'s disease, allergy, anaphylactic shock, immune complex disease, organ ischemia, reperfusion injury, organ necrosis, hay fever, sepsis, septicemia, endotoxic shock, cachexia, hyperpyrexia, eosinophilic granuloma, granulomatosis, sarcoidosis, septic abortion, epididymitis, vaginitis, prostatitis, urethritis, bronchitis, emphysema, rhinitis, pneumonitits, pneumotransmicroscopicsilicovolcanoconiosis, alvealitis, bronchiolitis, pharyngitis, pleurisy, sinusitis, influenza, respiratory syncytial virus infection, HIV infection, hepatitis B virus infection, hepatitis C virus infection, disseminated bacteremia, Dengue fever, candidiasis, malaria, filariasis, amebiasis, hydatid cysts, burns, dermatitis, dermatomyositis, sunburn, urticaria, warts, wheals, vasulitis, angiitis, endocarditis, arteritis, atherosclerosis, thrombophlebitis, pericarditis, myocarditis, myocardial ischemia, periarteritis nodosa, rheumatic fever, Alzheimer'"'"'s disease, coeliac disease, congestive heart failure, adult respiratory distress syndrome, meningitis, encephalitis, multiple sclerosis, cerebral infarction, cerebral embolism, Guillame-Barre syndrome, neuritis, neuralgia, spinal cord injury, paralysis, uveitis, arthritides, arthralgias, osteomyelitis, fasciitis, Paget'"'"'s disease, gout, periodontal disease, rheumatoid arthritis, synovitis, myasthenia gravis, thyroiditis, systemic lupus erythematosis, Goodpasture'"'"'s syndrome, Behcet'"'"'s syndrome, allograft rejection, graft-versus-host disease, Type I diabetes, ankylosing spondylitis, Berger'"'"'s disease, Reiter'"'"'s syndrome and Hodgkin'"'"'s disease.

6. The method of claim 5 wherein the condition is selected form sepsis, endotoxic shock, allograft rejection, rheumatoid arthritis, adult respiratory distress syndrome, asthma, systemic lupus erythematosis, pancreatitis, peritonitis, burns, myocardial ischemia, allograft rejection, graft-versus-host disease, congestive heart failure, organ ischemia, reperfusion injury, cachexia and cystic fibrosis.

7. The method of claim 5 wherein the condition is selected form appendicitis, ulcerative colitis, Crohn'"'"'s disease, allergy, reperfusion injury, systemic lupus erythematosus, hepatitis, Behcet'"'"'s syndrome, multiple sclerosis and atherosclerosis.

8. The method of claim 5 wherein said vagus nerve activity is stimulated at a peripheral distal location.

9. The method of claim 5 wherein said vagus nerve activity is stimulated in the cervical region.

10. The method of claim 5 wherein ganglions or post-ganglionic neurons are stimulated.

11. The method of claim 5 wherein the efferent vagus nerve is stimulated.

12. The method of claim 5 wherein the afferent vagus nerve is stimulated.

13. A method for treating a subject suffering from, or at risk for, ileus, comprising stimulating the vagus nerve in a subject with an electrical signal, wherein the signal voltage is from 0.01 Volt to 1 Volt.

14. The method of claim 13 wherein the signal voltage is from 0.01 Volt to 0.05 Volt.

15. The method of claim 13 wherein pulse width is from 0.1 ms to 5 ms;

signal frequency is from 0.1 Hz to 30 Hz; and

signal on-time is from 1 second to 120 seconds.

16. The method of claim 13 wherein signal voltage is from 0.01 Volt to 0.05 Volt;

pulse width is from 0.1 ms to 0.5 ms;

signal frequency is from 10 Hz to 30 Hz; and

signal on-time is from 20 seconds to 40 seconds.

17. The method of claim 13, wherein ileus is a post-operative ileus.

18. The method of claim 13, wherein ileus is treated pre-operatively.

19. The method of claim 18, wherein ileus is treated up to 48 hours before surgery.

20. The method of claim 13, wherein ileus is treated peri-operatively.

21. The method of claim 13, wherein ileus is treated post-operatively.

22. The method of claim 21, wherein ileus is treated up to 48 hours after surgery.

23. The method of claim 14, wherein ileus is treated by stimulating vagus nerve endotracheally or esophageally.

24. A method for treating a subject suffering from, or at risk for, an inflammatory disorder, comprising stimulating the vagus nerve in a subject with an electrical signal, wherein the signal voltage is from 0.01 Volt to 1 Volt, pulse width is from 0.1 ms to 5 ms;

signal frequency is from 0.1 Hz to 30 Hz;

signal on-time is from 1 second to 120 seconds; and

signal off-time is over 2 hours.

25. The method of claim 24 wherein the signal off-time is from 2 hours to 24 hours.

26. A method for treating a subject suffering from, or at risk for ileus, comprising stimulating the vagus nerve in a subject with an electrical signal, wherein the signal voltage is from 0.01 Volt to 1 Volt, pulse width is from 0.1 ms to 5 ms;

signal frequency is from 0.1 Hz to 30 Hz;

signal on-time is from 1 second to 120 seconds; and

signal off-time is over 2 hours.

27. An electrical signal generator for treating a subject suffering from, or at risk for, an inflammatory disorder, comprising:

an electrode assembly for delivering an electrical signal to the vagus nerve of the subject; and

a controller controlling the electrical signal by limiting the signal voltage to a range from 0.01 Volt to 1 Volt.

28. The signal generator of claim 27 wherein the signal voltage is limited to a range from 0.01 Volt to 0.05 Volt.

29. The signal generator of claim 27, the controller limiting pulse width to a range from 0.1 ms to 5 ms;

signal frequency to a range from 0.1 Hz to 30 Hz; and

signal on-time to a range from 1 second to 120 seconds.

30. The signal generator of claim 27, the controller limiting signal voltage to a range from 0.01 Volt to 0.05 Volt;

pulse width to a range from 0.1 ms to 0.5 ms;

signal frequency to a range from 10 Hz to 30 Hz; and

signal on-time to a range from 20 seconds to 40 seconds.

31. An electrical signal generator, comprising:

an electrode assembly for delivering an electrical signal to the vagus nerve of the subject; and

a controller controlling the electrical signal by limiting the signal voltage to a range from 0.01 Volt to 1 Volt, pulse width to a range from 0.1 ms to 5 ms;

signal frequency to a range from 0.1 Hz to 30 Hz;

signal on-time to a range from 1 second to 120 seconds; and

signal off-time to a range of over 2 hours.

32. The signal generator of claim 31, the controller limiting the signal off-time to a range from 2 hours to 24 hours.

33. A method for treating a subject suffering from, or at risk for, an inflammatory disorder, comprising stimulating the vagus nerve in a subject with an electrical signal, wherein the signal voltage is from 0.01 Volt to 1 Volt,

wherein the inflammatory disorder is selected from the group consisting of ileus, appendicitis, peptic ulcer, gastric ulcer, duodenal ulcer, peritonitis, pancreatitis, ulcerative colitis, pseudomembranous colitis, acute colitis, ischemic colitis, diverticulitis, epiglottitis, achalasia, cholangitis, cholecystitits, hepatitis, Crohn'"'"'s disease, enteritis, Whipple'"'"'s disease, allergy, anaphylactic shock, immune complex disease, organ ischemia, reperfusion injury, organ necrosis, hay fever, sepsis, septicemia, endotoxic shock, cachexia, hyperpyrexia, eosinophilic granuloma, granulomatosis, sarcoidosis, septic abortion, epididymitis, vaginitis, prostatitis, urethritis, bronchitis, emphysema, rhinitis, pneumonitits, pneumoultramicroscopicsilicovolcanoconiosis, alvealitis, bronchiolitis, pharyngitis, pleurisy, sinusitis, influenza, respiratory syncytial virus infection, HIV infection, hepatitis B virus infection, hepatitis C virus infection, herpes virus infection disseminated bacteremia, Dengue fever, candidiasis, malaria, filariasis, amebiasis, hydatid cysts, burns, dermatitis, dermatomyositis, sunburn, urticaria, warts, wheals, vasulitis, angiitis, endocarditis, arteritis, atherosclerosis, thrombophlebitis, pericarditis, myocarditis, myocardial ischemia, periarteritis nodosa, rheumatic fever, Alzheimer'"'"'s disease, coeliac disease, congestive heart failure, adult respiratory distress syndrome, meningitis, encephalitis, multiple sclerosis, cerebral infarction, cerebral embolism, Guillame-Barre syndrome, neuritis, neuralgia, spinal cord injury, paralysis, uveitis, arthritides, arthralgias, osteomyelitis, fasciitis, Paget'"'"'s disease, gout, periodontal disease, rheumatoid arthritis, synovitis, myasthenia gravis, thyroiditis, systemic lupus erythematosis, Goodpasture'"'"'s syndrome, Behcet'"'"'s syndrome, allograft rejection, graft-versus-host disease, Type I diabetes, ankylosing spondylitis, Berger'"'"'s disease, Reiter'"'"'s syndrome and Hodgkin'"'"'s disease.