ACTIVATION OF TRPA1+ NOCICEPTORS IN THE VAGUS NERVE ATTENUATES SYSTEMIC INFLAMMATION
Methods are disclosed for treating inflammation and sepsis and for promoting thermoregulation by activating neurons expressing TRPA1 in the vagus nerve.
1 . A method of suppressing or ameliorating inflammation, promoting thermoregulation, and/or treating sepsis in a subject comprising activating neurons expressing the ion channel designated transient receptor potential cation channel, subfamily A, member 1 (TRPA1) in the subject's vagus nerve effective to suppress or ameliorate inflammation, promote thermoregulation, and/or treat sepsis in a subject.
2 . The method of claim 1 , wherein TRPA1-positive neurons are activated by administering a TRPA1 nociceptor agonist to the subject.
3 . The method of claim 1 , wherein the method of suppressing inflammation, promoting thermoregulation, and/or treating sepsis is activated by selectively stimulating vagus nerve fibers expressing TRPA1 nociceptors in the subject.
4 . The method of claim 3 , comprising activating vagus nerve afferents.
5 . The method of claim 1 , wherein a photochemical activator is administered to the subject and TRPA1+ nociceptors are activated using optogenetic stimulation.
6 . The method of claim 5 , wherein optovin is administered to the subject and TRPA1+ nociceptors are activated using optogenetic stimulation.
7 . The method of claim 1 , wherein the subject has sepsis.
8 . The method of claim 1 , wherein the subject has endotoxemia, septicemia or septic shock.
9 . The method of claim 1 , wherein activation of TRPA1+ neurons attenuates serum levels of one or more pro-inflammatory cytokines.
10 . The method of claim 9 , wherein activation of TRPA1+ neurons attenuates serum levels of tumor necrosis factor (TNF).
11 . A method of suppressing or ameliorating fever in a subject comprising administering to the subject an antagonist of TRPA1 in amount effective to suppress or ameliorate fever in a subject.
12 . A method of activating an immune response in an immunosuppressed subject comprising administering to the subject an antagonist of TRPA1 in amount effective to induce an immune response in a subject.
13 . The method of claim 1 , wherein the subject is human.