title: Kilohertz frequency nerve block enhances anti-inflammatory effects of vagus nerve stimulation.
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.
authors.affiliation: Georgia Institute of Technology, Department of Biomedical Engineering, Atlanta, GA, 30332 USA.|Georgia Institute of Technology, Bioengineering Graduate Program, Atlanta, GA, 30332 USA.|Georgia Institute of Technology, Neural Engineering Center, Atlanta, GA, 30332 USA.
authors.forename: Yogi A
authors.initials: YA
authors.lastname: Patel
authors.affiliation: Duke University, Department of Biomedical Engineering, Durham, NC 27708 USA.
authors.forename: Tarun
authors.initials: T
authors.lastname: Saxena
authors.affiliation: Duke University, Department of Biomedical Engineering, Durham, NC 27708 USA.
authors.forename: Ravi V
authors.initials: RV
authors.lastname: Bellamkonda
authors.affiliation: Georgia Institute of Technology, Department of Biomedical Engineering, Atlanta, GA, 30332 USA.|Georgia Institute of Technology, Bioengineering Graduate Program, Atlanta, GA, 30332 USA.|Georgia Institute of Technology, Neural Engineering Center, Atlanta, GA, 30332 USA.|Georgia Institute of Technology, School of Electrical and Computer Engineering, Atlanta, GA 30332 USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Butera
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D004525:Efferent Pathways / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009407:Nerve Block / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000209:etiology / Q000628:therapy*; D014630:Vagus Nerve / Q000502:physiology*; D055536:Vagus Nerve Stimulation / Q000379:methods*
chemical_list: D008070:Lipopolysaccharides