Treating inflammatory disorders by stimulation of the cholinergic anti-inflammatory pathway
View Patent ↗Described herein are methods for treating a subject suffering from or at risk for a condition mediated by an inflammatory cytokine cascade, by electrically or mechanically stimulating vagus nerve activity in an amount sufficient to inhibit the inflammatory cytokine cascade.
1. A method of treating an inflammation in a patient, the method comprising:
stimulating, in a patient suffering from inflammation, the patient's vagus nerve with an electrical signal to achieve a therapeutic effect for treating the inflammation, wherein the signal current is from 1 mA to 100 mA, the signal voltage is from 0.01 Volts to 5 Volts, the pulse width is from 0.1 ms to 5 ms, the signal frequency is from 0.1 Hz to 30 Hz, and the signal on-time is from 1 second to 120 seconds, wherein the stimulation is transcutaneous stimulation of the vagus nerve;
limiting the stimulation of the vagus nerve to a frequency of between 0.1 Hz and 30 Hz; and
re-stimulating, by transcutaneous stimulation, the patient's vagus nerve after waiting for an off-time of at least 2 hours and prior to dissipation of the therapeutic effect for treating the inflammation, wherein the therapeutic effect persists for at least 2 hours after stimulation has ended.
2. The method of claim 1 wherein the off-time before the vagus nerve is re-stimulated is from 2 hours to 24 hours.
3. The method of claim 1 , wherein the off-time before the vagus nerve is re-stimulated is between about 16 and about 30 hours.
4. The method of claim 1 , further comprising monitoring the effect of the stimulation on inflammation in the patient.
5. The method of claim 1 , further comprising determining the level of a pro-inflammatory cytokine prior to stimulation.
6. The method of claim 1 , wherein the signal current is between 1 mA to 5 mA.
7. The method of claim 1 , wherein the therapeutic effect is dissipated by 72 hours after stimulation has ended.
8. The method of claim 1 , wherein stimulating comprises stimulating in a patient suffering from inflammation due to rheumatoid arthritis.
9. A method of treating inflammation in a patient, the method comprising:
applying an electrode to a patient suffering from a chronic inflammatory disorder;
stimulating, by transcutaneous stimulation, in the patient suffering from inflammation the patient's vagus nerve with an electrical signal from the electrode to achieve a therapeutic effect for treating the inflammation, wherein the signal current is from 1 mA to 100 mA, 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;
limiting the stimulation of the vagus nerve to a frequency of between 0.1 Hz and 30 Hz; and
re-stimulating, by transcutaneous stimulation, the patient's vagus nerve after waiting for an off-time of at least 2 hours and prior to dissipation of the therapeutic effect for treating the inflammation, wherein the therapeutic effect persists for at least 2 hours after stimulation has ended.
10. The method of claim 9 , wherein the chronic 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, pneumonitis, 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.
11. The method of claim 9 wherein the off-time before the vagus nerve is re-stimulated is from 2 hours to 24 hours.
12. The method of claim 9 , wherein the off-time before the vagus nerve is re-stimulated is between about 16 and about 30 hours.
13. The method of claim 9 , further comprising monitoring the effect of the stimulation on inflammation in the patient.
14. The method of claim 9 , further comprising determining the level of a pro-inflammatory cytokine prior to stimulation.
15. The method of claim 9 , wherein the chronic inflammatory disorder is rheumatoid arthritis.
16. A method of treating an inflammation in a patient, the method comprising:
stimulating, in a patient suffering from inflammation, the patient's vagus nerve by transcutaneous simulation, with an electrical signal to achieve a therapeutic effect for treating the inflammation, wherein the signal current is from 1 mA to 100 mA, the signal voltage is from 0.01 Volts to 5 Volts, the pulse width is from 0.1 ms to 5 ms, the signal frequency is from 0.1 Hz to 30 Hz, and the signal on-time is from 1 second to 120 seconds;
limiting the stimulation of the vagus nerve to a frequency of between 0.1 Hz and 30 Hz; and
re-stimulating the patient's vagus nerve by transcutaneous stimulation, after waiting for an off-time of at least 2 hours and prior to dissipation of the therapeutic effect for treating the inflammation, wherein the therapeutic effect persists for at least 2 hours after stimulation has ended, wherein the duration of the signal on-time is less than 1% of the duration of the signal off-time.
17. The method of claim 16 , wherein stimulating comprises stimulating in a patient suffering from inflammation due to rheumatoid arthritis.