Peripheral nerve stimulation and immunity: the expanding opportunities for providing mechanistic insight and therapeutic intervention

Abstract

Pre-clinical research advances our understanding of the vagus nerve-mediated regulation of immunity and clinical trials successfully utilize electrical vagus nerve stimulation in the treatment of patients with inflammatory disorders. This symbiotic relationship between pre-clinical and clinical research exploring the vagus nerve-based ‘inflammatory reflex’ has substantially contributed to establishing the field of bioelectronic medicine. Recent studies identify a crosstalk between the vagus nerve and other neural circuitries in controlling inflammation and delineate new neural immunoregulatory pathways. Here we outline current mechanistic insights into the role of vagal and non-vagal neural pathways in neuro-immune communication and inflammatory regulation. We also provide a timely overview of expanding opportunities for bioelectronic neuromodulation in the treatment of various inflammatory disorders.

International consensus recommendations for management of new onset refractory status epilepticus including febrile infection‐related epilepsy syndrome: Statements and supporting evidence

“…One case report of successful rapid titration of VNS parameters in a pediatric patient has been published, 108 and two case reports in adults also report positive effects in the acute 109 and postacute 110 phases. However, based on the possible anti‐inflammatory effect of VNS 111 and the long‐term use in several other forms of therapy‐refractory epilepsies, including RSE, 112–114 neuromodulation with VNS can also play a role in NORSE/FIRES and should be considered. Likewise, recent case reports of positive effects using brain‐responsive neurostimulation in FIRES 115 and in autoimmune encephalitis 116 as well as a recent review on neuromodulation in SRSE 117 indicate a need for further studies in these areas. Current evidence does not support the usefulness of deep brain stimulation (DBS) for postacute epilepsy (M = 8, MA = 8, MP = 7.5, LA = 70.8%, LD = 6.3%).The use of DBS in NORSE has been highlighted in a case report where centromedian thalamic nuclei DBS (in combination with anakinra) reduced the burden of generalized seizures but had no effect on focal seizures in a patient with medically intractable epilepsy following FIRES 118 .…”

Understanding the Pivotal Role of the Vagus Nerve in Health from Pandemics

“…As diseases are already or soon to be diagnosed earlier, minimally invasive VNS modalities should also be proposed as a first-line treatment in several indications [ 54 , 105 ]. Remarkably, transcutaneous auricular VNS was recently advocated for the treatment of endometriosis [ 106 ], which is especially interesting since the diagnosis of endometriosis has become available with a simple salivary test [ 107 ].…”

“…As a consequence, vagus nerve stimulation is a powerful anti-inflammatory tool (see [ 54 ] for a recent review), provided the metabolic needs are met. Today, the anti-inflammatory properties of drugs are even assessed according to their vagus-nerve-dependent effects [ 55 ].…”

Strategies for precision vagus neuromodulation

“…The vagus innervates most visceral organs, including the heart, lungs, liver, spleen, and gastrointestinal tract. Therefore, only the concerned branch of the vagus nerve can be targeted without disturbing the physiology of other organs (Falvey et al 2022 ). This approach has been used before in autonomic neuromodulation, in stellate ganglion stimulation for modulation of atrio-ventricular conduction (Zipes et al 1974 ), and later applied to the vagal gastric branch for modulating gallbladder responses (Furukawa and Okada 1992 ).…”