The strange case of the ear and the heart: The auricular vagus nerve and its influence on cardiac control

Murray, Aaron; Atkinson, Lucy; Mahadi, Mohd Kaisan; Deuchars, Susan A.; Deuchars, Jim

doi:10.1016/j.autneu.2016.06.004

Cited by 75 publications

(57 citation statements)

References 70 publications

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“…An alternate pathway could also have been activated by the sGVS, namely a branch of the vagus nerve that originates in the tragus of the external ear and projects to the NTS and the dorsal motor nucleus of the vagus (73). Therefore stimulation of the tragal branch of the vagus could have affected the function of the NTS, namely its control of the baroreflex, possibly causing modification of the baroreflex sensitivity that was observed with continued stimulation.…”

Section: Discussionmentioning

confidence: 99%

Vestibular Activation Habituates the Vasovagal Response in the Rat

et al. 2017

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Vasovagal syncope is a significant medical problem without effective therapy, postulated to be related to a collapse of baroreflex function. While some studies have shown that repeated static tilts can block vasovagal syncope, this was not found in other studies. Using anesthetized, male Long–Evans rats that were highly susceptible to generation of vasovagal responses, we found that repeated activation of the vestibulosympathetic reflex (VSR) with ±2 and ±3 mA, 0.025 Hz sinusoidal galvanic vestibular stimulation (sGVS) caused incremental changes in blood pressure (BP) and heart rate (HR) that blocked further generation of vasovagal responses. Initially, BP and HR fell ≈20–50 mmHg and ≈20–50 beats/min (bpm) into a vasovagal response when stimulated with Sgv\S in susceptible rats. As the rats were continually stimulated, HR initially rose to counteract the fall in BP; then the increase in HR became more substantial and long lasting, effectively opposing the fall in BP. Finally, the vestibular stimuli simply caused an increase in BP, the normal sequence following activation of the VSR. Concurrently, habituation caused disappearance of the low-frequency (0.025 and 0.05 Hz) oscillations in BP and HR that must be present when vasovagal responses are induced. Habituation also produced significant increases in baroreflex sensitivity (p < 0.001). Thus, repeated low-frequency activation of the VSR resulted in a reduction and loss of susceptibility to development of vasovagal responses in rats that were previously highly susceptible. We posit that reactivation of the baroreflex, which is depressed by anesthesia and the disappearance of low-frequency oscillations in BP and HR are likely to be critically involved in producing resistance to the development of vasovagal responses. SGVS has been widely used to activate muscle sympathetic nerve activity in humans and is safe and well tolerated. Potentially, it could be used to produce similar habituation of vasovagal syncope in humans.

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Section: Discussionmentioning

confidence: 99%

Vestibular Activation Habituates the Vasovagal Response in the Rat

et al. 2017

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“…Hitherto, it has been unclear whether the autonomic effects of auricular tVNS are the result of the activation of the hypothesised afferent central targets of the vagus system (ear → brain → vagus nerve → organ) or whether there is direct activation of the efferent vagal projections from the ear to body organs (ear → vagus → heart) (Murray et al ; Fig. ).…”

Section: Contemporary Studies Exploring the Cutaneous Distribution Ofmentioning

confidence: 99%

The anatomical basis for transcutaneous auricular vagus nerve stimulation

et al. 2019

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The array of end organ innervations of the vagus nerve, coupled with increased basic science evidence, has led to vagus nerve stimulation (VNS) being explored as a management option in a number of clinical disorders, such as heart failure, migraine and inflammatory bowel disease. Both invasive (surgically implanted) and non‐invasive (transcutaneous) techniques of VNS exist. Transcutaneous VNS (tVNS) delivery systems rely on the cutaneous distribution of vagal afferents, either at the external ear (auricular branch of the vagus nerve) or at the neck (cervical branch of the vagus nerve), thus obviating the need for surgical implantation of a VNS delivery device and facilitating further investigations across a wide range of uses. The concept of electrically stimulating the auricular branch of the vagus nerve (ABVN), which provides somatosensory innervation to several aspects of the external ear, is relatively more recent compared with cervical VNS; thus, there is a relative paucity of literature surrounding its operation and functionality. Despite the increasing body of research exploring the therapeutic uses of auricular transcutaneous VNS (tVNS), a comprehensive review of the cutaneous, intracranial and central distribution of ABVN fibres has not been conducted to date. A review of the literature exploring the neuroanatomical basis of this neuromodulatory therapy is therefore timely. Our review article explores the neuroanatomy of the ABVN with reference to (1) clinical surveys examining Arnold’s reflex, (2) cadaveric studies, (3) fMRI studies, (4) electrophysiological studies, (5) acupuncture studies, (6) retrograde tracing studies and (7) studies measuring changes in autonomic (cardiovascular) parameters in response to auricular tVNS. We also provide an overview of the fibre composition of the ABVN and the effects of auricular tVNS on the central nervous system. Cadaveric studies, of which a limited number exist in the literature, would be the ‘gold‐standard’ approach to studying the cutaneous map of the ABVN; thus, there is a need for more such studies to be conducted. Functional magnetic resonance imaging (fMRI) represents a useful surrogate modality for discerning the auricular sites most likely innervated by the ABVN and the most promising locations for auricular tVNS. However, given the heterogeneity in the results of such investigations and the various limitations of using fMRI, the current literature lacks a clear consensus on the auricular sites that are most densely innervated by the ABVN and whether the brain regions secondarily activated by electrical auricular tVNS depend on specific parameters. At present, it is reasonable to surmise that the concha and inner tragus are suitable locations for vagal modulation. Given the therapeutic potential of auricular tVNS, there remains a need for the cutaneous map of the ABVN to be further refined and the effects of various stimulation parameters and stimulation sites to be determined.

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“…; Murray et al . ). The tragus is innervated by a purely sensory branch of the vagus nerve, known as the auricular branch of the vagus, which could explain the significant sympatho‐inhibitory effects observed with stimulating this region, considering the findings of Schwartz et al .…”

Section: Introductionmentioning

confidence: 97%

Mechanisms underpinning sympathetic nervous activity and its modulation using transcutaneous vagus nerve stimulation

Deuchars

Lall

Clancy

et al. 2017

Experimental Physiology

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New Findings What is the topic of this review? This review briefly considers what modulates sympathetic nerve activity and how it may change as we age or in pathological conditions. It then focuses on transcutaneous vagus nerve stimulation, a method of neuromodulation in autonomic cardiovascular control. What advances does it highlight? The review considers the pathways involved in eliciting the changes in autonomic balance seen with transcutaneous vagus nerve stimulation in relationship to other neuromodulatory techniques. The autonomic nervous system, consisting of the sympathetic and parasympathetic branches, is a major contributor to the maintenance of cardiovascular variables within homeostatic limits. As we age or in certain pathological conditions, the balance between the two branches changes such that sympathetic activity is more dominant, and this change in dominance is negatively correlated with prognosis in conditions such as heart failure. We have shown that non‐invasive stimulation of the tragus of the ear increases parasympathetic activity and reduces sympathetic activity and that the extent of this effect is correlated with the baseline cardiovascular parameters of different subjects. The effects could be attributable to activation of the afferent branch of the vagus and, potentially, other sensory nerves in that region. This indicates that tragus stimulation may be a viable treatment in disorders where autonomic activity to the heart is compromised.

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The strange case of the ear and the heart: The auricular vagus nerve and its influence on cardiac control

Cited by 75 publications

References 70 publications

Vestibular Activation Habituates the Vasovagal Response in the Rat

Vestibular Activation Habituates the Vasovagal Response in the Rat

The anatomical basis for transcutaneous auricular vagus nerve stimulation

Mechanisms underpinning sympathetic nervous activity and its modulation using transcutaneous vagus nerve stimulation

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