How Is the Norepinephrine System Involved in the Antiepileptic Effects of Vagus Nerve Stimulation?

Vagus Nerve Stimulation (VNS) is an adjunctive treatment for patients suffering from inoperable drug-resistant epilepsy. Although a complete understanding of the mediators involved in the antiepileptic effects of VNS and their complex interactions is lacking, VNS is known to trigger the release of neurotransmitters that have seizure-suppressing effects. In particular, norepinephrine (NE) is a neurotransmitter that has been associated with the clinical effects of VNS by preventing seizure development and by inducing long-term plastic changes that could restore a normal function of the brain circuitry. However, the biological requisites to become responder to VNS are still unknown. In this review, we report evidence of the critical involvement of NE in the antiepileptic effects of VNS in rodents and humans. Moreover, we emphasize the hypothesis that the functional integrity of the noradrenergic system could be a determining factor to obtain clinical benefits from the therapy. Finally, encouraging avenues of research involving NE in VNS treatment are discussed. These could lead to the personalization of the stimulation parameters to maximize the antiepileptic effects and potentially improve the response rate to the therapy

Transcutaneous auricular VNS applied to experimental pain: A paired behavioral and EEG study using thermonociceptive CO2 laser.

Transcutaneous auricular Vagal Nerve Stimulation (taVNS) is a non-invasive neurostimulation technique with potential analgesic effects. Several studies based on subjective behavioral responses suggest that taVNS modulates nociception differently with either pro-nociceptive or anti-nociceptive effects. This study aimed to characterize how taVNS alters pain perception, by investigating its effects on event-related potentials (ERPs) elicited by different types of spinothalamic and lemniscal somatosensory stimuli, combined with quantitative sensory testing (detection threshold and intensity ratings). We performed 3 experiments designed to study the time-dependent effects of taVNS and compare with standard cervical VNS (cVNS). In Experiment 1, we assessed the effects of taVNS after 3 hours of stimulation. In Experiment 2, we focused on the immediate effects of the duty cycle (OFF vs. ON phases). Experiments 1 and 2 included 22 and 15 healthy participants respectively. Both experiments consisted of a 2-day cross-over protocol, in which subjects received taVNS and sham stimulation sequentially. In addition, subjects received a set of nociceptive (thermonociceptive CO2 laser, mechanical pinprick) and non-nociceptive (vibrotactile, cool) stimuli, for which we recorded detection thresholds, intensity of perception and ERPs. Finally, in Experiment 3, we tested 13 epileptic patients with an implanted cVNS by comparing OFF vs. ON cycles, using a similar experimental procedure. Neither taVNS nor cVNS appeared to modulate the cerebral and behavioral aspects of somatosensory perception. The potential effect of taVNS on nociception requires a cautious interpretation, as we found no objective change in behavioral and cerebral responses to spinothalamic and lemniscal somatosensory stimulations

Transcutaneous auricular VNS applied to experimental pain: A paired behavioral and EEG study using thermonociceptive CO2 laser

Background Transcutaneous auricular Vagal Nerve Stimulation (taVNS) is a non-invasive neurostimulation technique with potential analgesic effects. Several studies based on subjective behavioral responses suggest that taVNS modulates nociception differently with either pro-nociceptive or anti-nociceptive effects. Objective This study aimed to characterize how taVNS alters pain perception, by investigating its effects on event-related potentials (ERPs) elicited by different types of spinothalamic and lemniscal somatosensory stimuli, combined with quantitative sensory testing (detection threshold and intensity ratings). Methods We performed 3 experiments designed to study the time-dependent effects of taVNS and compare with standard cervical VNS (cVNS). In Experiment 1, we assessed the effects of taVNS after 3 hours of stimulation. In Experiment 2, we focused on the immediate effects of the duty cycle (OFF vs. ON phases). Experiments 1 and 2 included 22 and 15 healthy participants respectively. Both experiments consisted of a 2-day cross-over protocol, in which subjects received taVNS and sham stimulation sequentially. In addition, subjects received a set of nociceptive (thermonociceptive CO2 laser, mechanical pinprick) and non-nociceptive (vibrotactile, cool) stimuli, for which we recorded detection thresholds, intensity of perception and ERPs. Finally, in Experiment 3, we tested 13 epileptic patients with an implanted cVNS by comparing OFF vs. ON cycles, using a similar experimental procedure. Results Neither taVNS nor cVNS appeared to modulate the cerebral and behavioral aspects of somatosensory perception. Conclusion The potential effect of taVNS on nociception requires a cautious interpretation, as we found no objective change in behavioral and cerebral responses to spinothalamic and lemniscal somatosensory stimulations. </jats:sec

Transcutaneous auricular VNS applied to experimental pain: a paired behavioral and EEG study using thermonociceptive CO2 laser

Transcutaneous Auricular taVNS is a non invasive treatment which was shown to modulate pain perception in humans, although with contrasting analgesic and pronociceptive effects. This study explores the behavioral and cerebral effects of taVNS on somatosensory evoked thermonociceptive CO2 laser pulses

Optimization of Vagus Nerve Therapy : a study of the behavioral and electrophysiological effects of transcutaneous VNS

With only 1/3 of refractory epileptic patients responding to vagus nerve stimulation (VNS) therapy, this intervention still needs further research. Transcutaneous-VNS (T-VNS) is a non-invasive device stimulating the auricular branch of the vagus nerve, which was suggested to affect pain perception. Thus, T-VNS effects on behavioral and brain responses to nociceptive and non-nociceptive somatosensory stimuli could account for potential biomarkers of VNS effectiveness. 5 healthy volunteers participated to the study. During a 2-day protocol, T-VNS was delivered on the left ear for 3 hours with randomized active stimulation (cymbae conchae) or active control (earlobe). Before and after T-VNS, nociceptive (CO2 laser recruiting either A-δ or C fibers; 128 mN pinprick) and non-nociceptive (vibrotactile; cool) stimuli were applied on the contralateral hand dorsum. Perception thresholds, intensity, and quality were retrieved as behavioral responses. Using scalp electroencephalography (EEG; sampling rate: 512 Hz), we recorded event-related potentials (ERPs) elicited by thermonociceptive, cool, and vibrotactile stimuli, delivered in separate blocks (40 stimuli per block), randomized across participants. Both active T-VNS and sham stimulation showed antinociceptive effects, reflected in a decrease of the amplitude of the ERPs elicited by thermonociceptive stimuli in 4 et 3 participants respectively. In contrast, no clear effect was found for behavioral responses, indicating a dissociation between ERPs and perception. These preliminary results suggest that the overall antinociceptive effect of t-VNS is rather unspecific, most probably resulting from the global stimulation of the auricular nerves rather than that of the sole vagal branch. Additional comparison with trigeminal stimulation and more participants are needed to increase statistical power and significance

High throughput production of enzymatic milk protein hydrolysates and screening of their mineral chelating properties

International audienc

High‑throughput production of enzymatic milk protein hydrolysates and screening of their mineral‑chelating properties: How can we identify milk protein concentrate-enzymes combinaisons that produce hydrolysates with the highest mineral-chelating capacities in terms of quantity and variety ?

International audienc

High‑throughput production of enzymatic milk protein hydrolysates and screening of their mineral‑chelating properties: How can we identify milk protein concentrate-enzymes combinaisons that produce hydrolysates with the highest mineral-chelating capacities in terms of quantity and variety ?

International audienc

How Is the Norepinephrine System Involved in the Antiepileptic Effects of Vagus Nerve Stimulation?

Vagus Nerve Stimulation (VNS) is an adjunctive treatment for patients suffering from inoperable drug-resistant epilepsy. Although a complete understanding of the mediators involved in the antiepileptic effects of VNS and their complex interactions is lacking, VNS is known to trigger the release of neurotransmitters that have seizure-suppressing effects. In particular, norepinephrine (NE) is a neurotransmitter that has been associated with the clinical effects of VNS by preventing seizure development and by inducing long-term plastic changes that could restore a normal function of the brain circuitry. However, the biological requisites to become responder to VNS are still unknown. In this review, we report evidence of the critical involvement of NE in the antiepileptic effects of VNS in rodents and humans. Moreover, we emphasize the hypothesis that the functional integrity of the noradrenergic system could be a determining factor to obtain clinical benefits from the therapy. Finally, encouraging avenues of research involving NE in VNS treatment are discussed. These could lead to the personalization of the stimulation parameters to maximize the antiepileptic effects and potentially improve the response rate to the therapy.</jats:p