TREATMENT OF INFLAMMATION BY NON-INVASIVE STIMULATION

• US 20160250097A9
• Filed: 03/13/2008
• Published: 09/01/2016
• Est. Priority Date: 03/25/2004
• Status: Abandoned Application

• Current Assignee: The Feinstein Institute for Medical Research (Northwell Health, Inc.)
• Original Assignee: The Feinstein Institute for Medical Research (Northwell Health, Inc.)
• Inventors: Tracey, Kevin J., Warren, Howland Shaw, Faltys, Michael Allen
• Application Number:
  US12/048,114
• Publication Number:
  US 20080249439A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61H 2205/027 Ears
• CPC Class Codes: A61H 23/00 Percussion or vibration massage, e.g. using supersonic vibration; Suction-vibration massage; Massage with moving diaphragms apparatus for passive exercising A61H1/00; generating or transmitting mechanical vibrations in general B06B
• CPC Class Codes: A61H 39/04 Devices for pressing such points, e.g. Shiatsu or AcupressureMassage or pressure on general areas A61H9/00 - A61H23/00

Abstract

Described herein are devices, systems and method for treating inflammatory disorders by modulating a subject'"'"'s inflammatory reflex. The method may include the step of non-invasively stimulating the inflammatory reflex (e.g., the vagus nerve, the splenic nerve, the hepatic nerve, the facial nerve, and the trigeminal nerve) of a subject in a manner which significantly reduces proinflammatory cytokines in the subject and/or provides a therapeutically effective treatment for the subject. Devices for non-invasively stimulating the inflammatory reflex may include a movable tip or actuator that is controlled to mechanically stimulate the ear. The devices may be hand-held or wearable, and may stimulate the cymba conchae region of the subject'"'"'s ear.

Claims

1. A method of treating an inflammatory disorder, the method comprising:

non-invasively stimulating a subject'"'"'s inflammatory reflex in a manner that significantly reduces proinflammatory cytokines in the subject.

2. The method of claim 1, wherein the non-invasive stimulation comprises mechanical stimulation of the subject'"'"'s cymba conchae region of their ear.

3. The method of claim 1, wherein the non-invasive stimulation comprises stimulation between about 50 and 500 Hz.

4. The method of claim 1, wherein the non-invasive stimulation comprises stimulation of less than 5 minutes.

5. The method of claim 1, wherein the non-invasive stimulation comprises stimulation for about 1 minute.

6. The method of claim 1, wherein the non-invasive stimulation comprises a temporal pattern that does not allow accommodation of mechanoreceptors in the region of stimulation during the stimulation period.

7. The method of claim 1, wherein the non-invasive stimulation comprises mechanical stimulation of the subject'"'"'s cymba conchae region of their ear for between about 50 and 500 Hz for about one minute.

8. The method of claims 1, wherein the non-invasive stimulation is applied to the subject'"'"'s area innervated by the seventh (facial) cranial nerve or cranial nerve V.

9. The method of claim 1, wherein the non-invasive stimulation is applied to at least one location selected from the subject'"'"'s cymba conchae of the ear, or helix of the ear.

10. The method of claim 1, wherein the non-invasive stimulation is applied to at least one point along the spleen meridian.

11. The method of claims 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, pneumotransmicroscopic silicovolcanoconiosis, 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, Type II diabetes, ankylosing spondylitis, Berger'"'"'s disease, Reiter'"'"'s syndrome, Hodgkin'"'"'s disease, ileus, hypertension, irritable bowel syndrome, myocardial infarction, sleeplessness, anxiety and stent trombosis.

12. The method of claims 1, wherein the inflammatory disorder is rheumatoid arthritis.

13. A method of treating an inflammatory disorder, the method comprising:

non-invasively stimulating a subject'"'"'s ear to stimulate the inflammatory reflex in a manner that significantly reduces the proinflammatory cytokines in the subject.

14. The method of claim 13, wherein the non-invasive stimulation comprises mechanical stimulation of the subject'"'"'s cymba conchae region of their ear.

15. The method of claim 13, wherein the non-invasive stimulation comprises stimulation between about 50 and 500 Hz.

16. The method of claim 13, wherein the non-invasive stimulation comprises stimulation of less than 5 minutes.

17. The method of claim 13, wherein the non-invasive stimulation comprises stimulation for about 1 minute.

18. The method of claim 13, wherein the non-invasive stimulation comprises a temporal pattern that does not allow accommodation of mechanoreceptors in the region of stimulation during the stimulation period.

19. The method of claim 13, wherein the non-invasive stimulation comprises mechanical stimulation of the subject'"'"'s cymba conchae region of their ear for between about 50 and 500 Hz for about one minute.

20. The method of claims 13, wherein the non-invasive stimulation is applied to the subject'"'"'s area innervated by the seventh (facial) cranial nerve or cranial nerve V.

21. The method of claim 13, wherein the non-invasive stimulation is applied to at least one location selected from the subject'"'"'s cymba conchae of the ear, or helix of the ear.

22. The method of claim 13, wherein the non-invasive stimulation is applied to at least one point along the spleen meridian.

23. The method of claims 13, 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, pneumotransmicroscopic silicovolcanoconiosis, 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, Type II diabetes, ankylosing spondylitis, Berger'"'"'s disease, Reiter'"'"'s syndrome, Hodgkin'"'"'s disease, ileus, hypertension, irritable bowel syndrome, myocardial infarction, sleeplessness, anxiety and stent trombosis.

24. The method of claims 13, wherein the inflammatory disorder is rheumatoid arthritis.

25. A method of treating an inflammatory disorder, the method comprising:

mechanically stimulating a subject'"'"'s ear to stimulate the inflammatory reflex in a manner that significantly reduces the proinflammatory cytokines in the subject.

26. The method of claim 25, wherein the non-invasive stimulation comprises mechanical stimulation of mechanoreceptors within the subject'"'"'s cymba conchae region of their ear.

27. The method of claim 25, wherein the non-invasive stimulation comprises stimulation between about 50 and 500 Hz.

28. The method of claim 25, wherein the non-invasive stimulation comprises stimulation of less than 5 minutes.

29. The method of claim 25, wherein the non-invasive stimulation comprises stimulation for about 1 minute.

30. The method of claim 25, wherein the non-invasive stimulation comprises a temporal pattern that does not allow accommodation of mechanoreceptors in the region of stimulation during the stimulation period.

31. The method of claim 25, wherein the non-invasive stimulation comprises mechanical stimulation of the subject'"'"'s cymba conchae region of their ear for between about 50 and 500 Hz for about one minute.

32. The method of claims 25, wherein the non-invasive stimulation is applied to the subject'"'"'s area innervated by the seventh (facial) cranial nerve or cranial nerve V.

33. The method of claim 25, wherein the non-invasive stimulation is applied to at least one location selected from the subject'"'"'s cymba conchae of the ear, or helix of the ear.

34. The method of claim 25, wherein the non-invasive stimulation is applied to at least one point along the spleen meridian.

35. The method of claims 25, 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, pneumotransmicroscopic silicovolcanoconiosis, 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, Type II diabetes, ankylosing spondylitis, Berger'"'"'s disease, Reiter'"'"'s syndrome, Hodgkin'"'"'s disease, ileus, hypertension, irritable bowel syndrome, myocardial infarction, sleeplessness, anxiety and stent trombosis.

36. The method of claims 25, wherein the inflammatory disorder is rheumatoid arthritis.

37. A method of treating an inflammatory disorder, the method comprising:

mechanically stimulating a subject'"'"'s cymba conchae region of the ear for less than five minutes in a manner that significantly reduces the proinflammatory cytokines in the subject.

38. A device for non-invasively stimulating a subject'"'"'s inflammatory reflex, the device comprising:

a movable distal tip region configured to mechanically stimulate at least a portion of a subject'"'"'s ear;

a handle; and

a driver configured to move the distal tip region between about 50 and 500 Hz.

39. The device of claim 38, further comprising a controller configured to control the driver so that it stimulates for less than 5 minutes.

40. The device of claim 38, wherein the driver comprises a motor.

41. The device of claim 38, wherein the driver comprises a voice coil.

42. The device of claim 38, wherein the distal tip region has a diameter of between about 35 mm and about 8 mm.

43. The device of claim 38, further comprising a frequency generator in communication with the driver.

44. A wearable device for non-invasively stimulating a subject'"'"'s inflammatory reflex, the device comprising:

an actuator configured to mechanically stimulate a subject'"'"'s cymba conchae;

a driver configured to move the distal tip region between about 50 and 500 Hz; and

an ear attachment region configured to secure to at least a portion of a subject'"'"'s ear.

45. The device of claim 44, further comprising an alert configured to indicate that the device should be worn.

46. The device of claim 44, further comprising a memory configured to record treatment parameters.

47. The device of claim 44, further comprising feedback to detect delivery of stimulation.

48. The device of claim 44, wherein the actuator is selected from the group consisting of:

electromagnet, bimorph, piezo crystal, electrostatic actuator, speaker coil, and rotating magnet or mass.

49. The device of claim 44, further comprising a driver circuit for controlling the amplitude, frequency, and duty cycle of the driver.

50. The device of claim 44, further comprising a device body including the ear attachment region configured to conform to the subject'"'"'s ear.

51. The device of claim 44, further comprising a therapy timer configured to limit the duration of stimulation.

52. The device of claim 44, further comprising a battery.