Lymphatic system neuromodulation and uses thereof
Methods are disclosed for preventing systemic infection or controlling metastases or providing a vaccine adjuvant in a subject, the methods comprising stimulating one or more peripheral nerves innervating one or more lymph nodes of the subject.
1. A method of inhibiting systemic infection by infectious pathogens in a subject, the method comprising electrical and/or magnetic stimulation of one or more peripheral nerves innervating one or more lymph nodes draining a site of infection in the subject to constrain the infectious pathogens from traveling through the subject's lymphatic system, wherein unconstrained travel of the infectious pathogens through the subject's lymphatic system leads to systemic infection, thereby inhibiting systemic infection by the infectious pathogens in the subject;
wherein the electrical stimulation of the one or more peripheral nerves comprises a train of 0.75 msec duration pulses applied at 2-20 Hz, or wherein the magnetic stimulation of the one or more peripheral nerves comprises a train of pulses applied at 2 Hz using an electromagnetic coil that creates a time-variable magnetic field.
2. The method of claim 1 , wherein the stimulation is applied after a penetrating injury to the subject's skin.
3. The method of claim 1 , wherein the infectious pathogens are bacteria.
4. The method of claim 1 , wherein the one or more peripheral nerves innervating the one or more lymph nodes drain a site of a penetrating injury to the subject's skin and stimulation of the one or more peripheral nerves innervating the one or more lymph nodes inhibits bacteremia and sepsis.
5. The method of claim 1 , wherein the stimulation of the one or more peripheral nerves comprises stimulation of femoral and sciatic nerves in the popliteal fascia.
6. The method of claim 1 , wherein the stimulation is electrical stimulation applied using a monopolar or bipolar needle electrode, a cluster of penetrating electrodes, percutaneous electrical nerve stimulation (PENS), transcutaneous electrical nerve stimulation (TENS), or a chronically implanted nerve stimulator.
7. The method of claim 1 , wherein the stimulation is applied for a duration of at least 1 minute.
8. The method of claim 1 , wherein the stimulation is applied in one session.
9. A method of inhibiting formation of metastases in a subject, the method comprising electrical and/or magnetic stimulation of one or more peripheral nerves innervating one or more lymph nodes draining a site of a primary tumor in the subject to restrict tumor cells and micrometastases from traveling through the subject's lymphatic system, wherein unrestricted travel of the tumor cells and micrometastases through the subject's lymphatic system leads to recolonization of cancer cells and formation of a metastatic tumor, thereby inhibiting the formation of metastases in the subject,
wherein the electrical stimulation of the one or more peripheral nerves comprises a train of 0.75 msec duration pulses applied at 2-20 Hz, or wherein the magnetic stimulation of the one or more peripheral nerves comprises a train of pulses applied at 2 Hz using an electromagnetic coil that creates a time-variable magnetic field.
10. The method of claim 9 , wherein the stimulation is electrical stimulation applied using a monopolar or bipolar needle electrode, a cluster of penetrating electrodes, percutaneous electrical nerve stimulation (PENS), transcutaneous electrical nerve stimulation (TENS), or a chronically implanted nerve stimulator.
11. A method of providing a vaccine adjuvant in a subject who has received a vaccine, the method comprising electrical and/or magnetic stimulation of one or more peripheral nerves innervating one or more lymph nodes of the subject who has received the vaccine to increase antibody production to an antigen present in the vaccine, thereby providing a vaccine adjuvant in the subject,
wherein the electrical stimulation of the one or more peripheral nerves comprises a train of 0.75 msec duration pulses applied at 2-20 Hz, or wherein the magnetic stimulation of the one or more peripheral nerves comprises a train of pulses applied at 2 Hz using an electromagnetic coil that creates a time-variable magnetic field.
12. The method of claim 11 , wherein the stimulation is electrical stimulation applied using a monopolar or bipolar needle electrode, a cluster of penetrating electrodes, percutaneous electrical nerve stimulation (PENS), transcutaneous electrical nerve stimulation (TENS), or a chronically implanted nerve stimulator.