Non-Pharmacological Approaches to Headaches: Non-Invasive Neuromodulation, Nutraceuticals, and Behavioral Approaches

Significant side effects or drug interactions can make pharmacological management of headache disorders very difficult. Non-conventional and non-pharmacological treatments are becoming increasingly used to overcome these issues. In particular, non-invasive neuromodulation, nutraceuticals, and behavioral approaches are well tolerated and indicated for specific patient categories such as adolescents and pregnant women. This paper aims to present the main approaches reported in the literature in the management of headache disorders. We therefore reviewed the available literature published between 2010 and 2020 and performed a narrative presentation for each of the three categories (non-invasive neuromodulation, nutraceuticals, and behavioral therapies). Regarding non-invasive neuromodulation, we selected transcranial magnetic stimulation, supraorbital nerve stimulation, transcranial direct current stimulation, non-invasive vagal nerve stimulation, and caloric vestibular stimulation. For nutraceuticals, we selected Feverfew, Butterbur, Riboflavin, Magnesium, and Coenzyme Q10. Finally, for behavioral approaches, we selected biofeedback, cognitive behavioral therapy, relaxation techniques, mindfulness-based therapy, and acceptance and commitment therapy. These approaches are increasingly seen as a valid treatment option in headache management, especially for patients with medication overuse or contraindications to drug treatment. However, further investigations are needed to consider the effectiveness of these approaches also with respect to the long-term effects.

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Rationale and design for a randomized, single-center, double-blind, sham-controlled study of non-invasive vagus nerve stimulation for treatment of post-traumatic headache

Neurology ◽

10.1212/wnl.0000000000008354 ◽

2019 ◽

Vol 93 (14 Supplement 1) ◽

pp. S1.1-S1

Author(s):

Bert Vargas ◽

Eric Liebler ◽

Stephen Bunt ◽

Charlene Supent-Bell

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Acute Treatment ◽

Preventive Therapy ◽

Efficacy And Safety ◽

Headache Disorders ◽

Double Blind ◽

Non Invasive ◽

Post Traumatic

ObjectiveEvaluate the efficacy and safety of non-invasive vagus nerve stimulation (nVNS) for the treatment of post-traumatic headache (PTH).BackgroundWorldwide, ∼69 million people per year sustain a traumatic brain injury (TBI), many of whom develop PTH. Clinicians often treat PTH with drugs approved for primary headache disorders, and many patients self-treat with over-the-counter agents but have inadequate pain relief. There has been little study of therapies for PTH, and safe, effective treatments are needed.Design/MethodsThis randomized, double-blind, sham-controlled, parallel-group pilot study is enrolling adults who present 1–4 weeks after a head injury, meet International Classification of Headache Disorders 3rd edition (ICHD-3) criteria for acute headache attributed to mild TBI, and have ≥2 headaches/week with a migraine or probable migraine phenotype. After a 2-week run-in period, subjects are randomly assigned (1:1 allocation) to receive daily preventive therapy and as-needed acute treatment with nVNS or a sham device. Preventive therapy consists of two 120-second stimulations 3 times daily. Acute treatment comprises 2 stimulations at headache onset and 2 stimulations 20 minutes after the start of initial treatment. Subjects are not to use acute rescue medication for 120 minutes post-treatment. One North American site will enroll ≤80 subjects. The expected duration is 12 months (enrollment, 9 months; participation, 14 weeks).ResultsThe primary effectiveness end point is decrease in pain (on a 7-point scale) 60 minutes post-treatment for all treated headache attacks. Secondary end points include decrease in the frequency of headache days between the run-in period and the last 2 weeks of the double-blind period and responder rates (ie, percentages of subjects with ≥50% decrease in attack frequency). The primary safety end point is the incidence of treatment-related serious adverse events.ConclusionsThis study will assess the efficacy and safety of nVNS as a novel therapy for PTH.

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Non-Invasive Neuromodulation Using Time-Varying Caloric Vestibular Stimulation

IEEE Journal of Translational Engineering in Health and Medicine ◽

10.1109/jtehm.2016.2615899 ◽

2016 ◽

Vol 4 ◽

pp. 1-10 ◽

Cited By ~ 9

Author(s):

Robert D. Black ◽

Lesco L. Rogers ◽

Kristen K. Ade ◽

Heather A. Nicoletto ◽

Heather D. Adkins ◽

...

Keyword(s):

Vestibular Stimulation ◽

Time Varying ◽

Non Invasive ◽

Caloric Vestibular Stimulation

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Anosognosia for Motor and Cognitive Deficit as a Clinical Manifestation of Ischemic Stroke: Review of Literature

Doctor Ru ◽

10.31550/1727-2378-2020-19-9-33-38 ◽

2020 ◽

Vol 19 (9) ◽

pp. 33-38

Author(s):

V.N. Grigorieva ◽

◽

T.A. Sorokina ◽

◽

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Neurological Deficit ◽

Cognitive Deficit ◽

Negative Impact ◽

Behavioral Therapy ◽

Vestibular Stimulation ◽

Medical Rehabilitation ◽

Stroke Patients ◽

Caloric Vestibular Stimulation

Objective of the Review: To present data from the latest research studies focusing on anosognosia for neurological deficit in patients with acute ischemic stroke. Key Points: Anosognosia for motor and cognitive deficit is a quite common disorder in acute ischemic stroke patients. This condition is of interest for neurologists because it manifests itself in an unusual way and has a negative impact on patients’ medical rehabilitation. The understanding of the pathophysiology of anosognosia and its neuroanatomical underpinnings is changing and improving. New information about approaches to the diagnosis and treatment of this condition is becoming available, making this review timely. Conclusion: Patients with acute ischemic stroke may have reduced perception of their neurological deficit and cognitive, emotional, and behavioral disorders. Hemispatial neglect is the most common cognitive disorder associated with anosognosia for paralysis. Medical rehabilitation of post-stroke patients with anosognosia is challenging and requires the participation of a multidisciplinary team and a differentiated approach, tailored to the type of anosognosia. At present, rehabilitation specialists have started discussing the possibility of therapeutic application of instrumental investigation techniques, such as caloric vestibular stimulation and transcranial brain stimulation, in addition to cognitive behavioral therapy. Keywords: reduced perception of disease, anosognosia, regulatory dysfunction, neglect, ischemic stroke.

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Vagus nerve stimulation for primary headache disorders: An anatomical review to explain a clinical phenomenon

Cephalalgia ◽

10.1177/0333102419833076 ◽

2019 ◽

Vol 39 (9) ◽

pp. 1180-1194 ◽

Cited By ~ 13

Author(s):

Dylan Jozef Hendrik Augustinus Henssen ◽

Berend Derks ◽

Mats van Doorn ◽

Niels Verhoogt ◽

Anne-Marie Van Cappellen van Walsum ◽

...

Keyword(s):

Vagus Nerve ◽

Trigeminal Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Primary Headache ◽

Solitary Tract ◽

Headache Disorders ◽

Primary Headache Disorders ◽

Non Invasive ◽

Stimulation Of

Background Non-invasive stimulation of the vagus nerve has been proposed as a new neuromodulation therapy to treat primary headache disorders, as the vagus nerve is hypothesized to modulate the headache pain pathways in the brain. Vagus nerve stimulation can be performed by placing an electrode on the ear to stimulate the tragus nerve, which contains about 1% of the vagus fibers. Non-invasive vagus nerve stimulation (nVNS) conventionally refers to stimulation of the cervical branch of the vagus nerve, which is made up entirely of vagal nerve fibers. While used interchangeably, most of the research to date has been performed with nVNS or an implanted vagus nerve stimulation device. However, the exact mechanism of action of nVNS remains hypothetical and no clear overview of the effectiveness of nVNS in primary headache disorders is available. Methods In the present study, the clinical trials that investigated the effectiveness, tolerability and safety of nVNS in primary headache disorders were systematically reviewed. The second part of this study reviewed the central connections of the vagus nerve. Papers on the clinical use of nVNS and the anatomical investigations were included based on predefined criteria, evaluated, and results were reported in a narrative way. Results The first part of this review shows that nVNS in primary headache disorders is moderately effective, safe and well-tolerated. Regarding the anatomical review, it was reported that fibers from the vagus nerve intertwine with fibers from the trigeminal, facial, glossopharyngeal and hypoglossal nerves, mostly in the trigeminal spinal tract. Second, the four nuclei of the vagus nerve (nuclei of the solitary tract, nucleus ambiguus, spinal nucleus of the trigeminal nerve and dorsal motor nucleus (DMX)) show extensive interconnections. Third, the efferents from the vagal nuclei that receive sensory and visceral input (i.e. nuclei of the solitary tract and spinal nucleus of the trigeminal nerve) mainly course towards the main parts of the neural pain matrix directly or indirectly via other vagal nuclei. Conclusion The moderate effectiveness of nVNS in treating primary headache disorders can possibly be linked to the connections between the trigeminal and vagal systems as described in animals.

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Non-invasive Nerve Stimulation and Cognitive Training to Improve Cognitive Performance in Healthy Older Adults

Case Medical Research ◽

10.31525/ct1-nct04276805 ◽

2020 ◽

Author(s):

Keyword(s):

Older Adults ◽

Cognitive Performance ◽

Cognitive Training ◽

Nerve Stimulation ◽

Healthy Older Adults ◽

Non Invasive

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Caloric vestibular stimulation in aphasic syndrome

Frontiers in Integrative Neuroscience ◽

10.3389/fnint.2013.00099 ◽

2013 ◽

Vol 7 ◽

Cited By ~ 6

Author(s):

David Wilkinson ◽

Rachael Morris ◽

William Milberg ◽

Mohamed Sakel

Keyword(s):

Vestibular Stimulation ◽

Caloric Vestibular Stimulation

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Long Term Effects of Low Frequency (10 Hz) Vagus Nerve Stimulation on EEG and Heart Rate Variability in Crohn's Disease: A Case Report

Brain Stimulation ◽

10.1016/j.brs.2014.08.001 ◽

2014 ◽

Vol 7 (6) ◽

pp. 914-916 ◽

Cited By ~ 26

Author(s):

Didier Clarençon ◽

Sonia Pellissier ◽

Valérie Sinniger ◽

Astrid Kibleur ◽

Dominique Hoffman ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Crohn’S Disease ◽

Case Report ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Low Frequency ◽

Long Term Effects

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Non-invasive vagus nerve stimulation reduced neuron-derived IL-1β and neuroinflammation in acute ischemic rat brain

Hemorrhagic Stroke ◽

10.1016/j.hest.2021.06.003 ◽

2021 ◽

Author(s):

Lisa Y Yang ◽

Kiran Bhaskar ◽

Jeffrey Thompson ◽

Kelsey Duval ◽

Michel Torbey ◽

...

Keyword(s):

Vagus Nerve ◽

Rat Brain ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Non Invasive

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Non-invasive vagus nerve stimulation boosts mood recovery after effort exertion

Psychological Medicine ◽

10.1017/s0033291720005073 ◽

2021 ◽

pp. 1-11

Author(s):

Magdalena Ferstl ◽

Vanessa Teckentrup ◽

Wy Ming Lin ◽

Franziska Kräutlein ◽

Anne Kühnel ◽

...

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Positive Mood ◽

Credible Interval ◽

Cognitive Effort ◽

Mood States ◽

Non Invasive ◽

Lower Baseline ◽

Open Question

Abstract Background Mood plays an important role in our life which is illustrated by the disruptive impact of aberrant mood states in depression. Although vagus nerve stimulation (VNS) has been shown to improve symptoms of depression, the exact mechanism is still elusive, and it is an open question whether non-invasive VNS could be used to swiftly and robustly improve mood. Methods Here, we investigated the effect of left- and right-sided transcutaneous auricular VNS (taVNS) v. a sham control condition on mood after the exertion of physical and cognitive effort in 82 healthy participants (randomized cross-over design) using linear mixed-effects and hierarchical Bayesian analyses of mood ratings. Results We found that 90 min of either left-sided or right-sided taVNS improved positive mood [b = 5.11, 95% credible interval, CI (1.39–9.01), 9.6% improvement relative to the mood intercept, BF10 = 7.69, pLME = 0.017], yet only during the post-stimulation phase. Moreover, lower baseline scores of positive mood were associated with greater taVNS-induced improvements in motivation [r = −0.42, 95% CI (−0.58 to −0.21), BF10 = 249]. Conclusions We conclude that taVNS boosts mood after a prolonged period of effort exertion with concurrent stimulation and that acute motivational effects of taVNS are partly dependent on initial mood states. Collectively, our results show that taVNS may help quickly improve affect after a mood challenge, potentially by modulating interoceptive signals contributing to the reappraisal of effortful behavior. This suggests that taVNS could be a useful add-on to current behavioral therapies.

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