Abstract
Efferent activation of the cervical vagus nerve (cVN) dampens systemic inflammatory processes, potentially modulating a wide-range of inflammatory pathological conditions. In contrast, afferent cVN activation amplifies systemic inflammatory processes, leading to activation of the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system through the greater splanchnic nerve (GSN), and elevation of pro-inflammatory cytokines. Ideally, to clinically implement anti-inflammatory therapy via cervical vagus nerve stimulation (cVNS) one should selectively activate the efferent pathway. Unfortunately, current implementations, in animal and clinical investigations, activate both afferent and efferent pathways. We paired cVNS with kilohertz electrical stimulation (KES) nerve block to preferentially activate efferent pathways while blocking afferent pathways. Selective efferent cVNS enhanced the anti-inflammatory effects of cVNS. Our results demonstrate that: (i) afferent, but not efferent, cVNS synchronously activates the GSN in a dose-dependent manner; (ii) efferent cVNS enabled by complete afferent KES nerve block enhances the anti-inflammatory benefits of cVNS; and (iii) incomplete afferent KES nerve block exacerbates systemic inflammation. Overall, these data demonstrate the utility of paired efferent cVNS and afferent KES nerve block for achieving selective efferent cVNS, specifically as it relates to neuromodulation of systemic inflammation.
Highlights
Are sufficient for elucidating acute effects in animal investigations, clinical translation of selective afferent or efferent cVNS requires a safe and effective alternative approach
We have previously shown that sinusoidal kilohertz electrical stimulation (KES) enables a safe, robust, and rapidly reversible block of nerve activity in the cVN7
We hypothesized that KES nerve block could be utilized to achieve a quick, reliable, and temporary virtual vagotomy for inhibiting activation of afferent pathways while delivering efferent cVNS (ecVNS)
Summary
Are sufficient for elucidating acute effects in animal investigations, clinical translation of selective afferent (acVNS) or efferent cVNS (ecVNS) requires a safe and effective alternative approach. When the virtual vagotomy is incomplete, the beneficial effects of ecVNS are partial This acute study demonstrates (i) the ability of KES nerve block to provide a method for virtually transecting nerves safely, robustly, and reversibly; (ii) paired delivery of ecVNS and afferent KES nerve block for modulation of systemic inflammatory processes; and (iii) quantitative criteria for evaluating the status of KES nerve block. This technique of paired delivery for achieving selective acVNS or ecVNS may benefit on-going investigations utilizing cVNS, when developing human bioelectronic medicines based upon laboratory findings
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
