Cluster headaches, neck instability and the trigeminal and vagus nerves

Ross Hauser, MD, Danielle R. Steilen-Matias, PA-C.

In this article, we will not examine which combination of medications, therapy, or neuromodulation techniques will work for you. If you are reading this article, it is unlikely you have had a long-term benefit from these treatments. What we will examine is something that may have been discussed with you briefly, that your headaches are coming from problems in your neck and possible compression of the vagus and trigeminal nerves.

Why so much confusion about getting treatment that can help my headaches?

A study from Harvard Medical School published in March 2019 in The Medical Clinics of North America (1) suggested that most headache patients seeking medical treatments for their headache symptoms will be diagnosed with a primary headache disorder, mostly migraine or tension-type headache. However, these patients may not be helped because there are other less commonly known primary headaches and secondary headaches that need to be considered in every patient presenting with a new onset or change in headache symptoms, and headache treatments are varied, one medication will not work for all headaches and giving the wrong medication will make the situation worse.

And this may be your history. A visit from specialist to specialist and the elimination of what you do not have to try to understand what you do have. And here you are, still looking for treatment for what you most certainly have: terrible headache-related pain.

Understanding “lesser-known” headache types

In the research above, a suggestion is made to start looking for less obvious or “lesser-known,” headaches. How can this help?

What are these “lesser-known” headaches? Have they been explained to you?

These headache types are explained below.

The research also notes that facial pain and neuralgias constitute a large and distinct group of head pains with separate evaluation and treatment approaches. This can cause confusion in treatment.

Neovascular headache syndromes are collectively termed trigeminal autonomic cephalalgia

The start and symptoms of several types of headaches including cluster, paroxysmal hemicranias, and some types of migraines are felt in whole or in part to be due to trigeminal-induced vasodilation of cerebral blood vessels. These neovascular headache syndromes are collectively termed trigeminal autonomic cephalalgia. They often have common features including:

Chronic paroxysmal hemicrania

In a June 2023 update (2) to the online publication, STATPearls at the National Library of Medicine specialists write; “Chronic paroxysmal hemicrania is a primary headache syndrome characterized by recurrent unilateral (one-sided) episodes of headache associated with cranial autonomic symptoms. Headaches are sharp and stabbing in nature and occur more than five times per day, up to forty times per day in some cases. Associated cranial autonomic features include ipsilateral lacrimation one-sided eye-redness), conjunctival injection (inflammation around the eye), nasal congestion, rhinorrhea (thin nasal discharge), facial flushing, eyelid edema, miosis (excessive constriction of the pupil of the eye), or mydriasis (dilation of the pupil), diaphoresis (excessive sweating), or aural fullness. The mean duration of the attack is 26 minutes, with a range of two minutes to nearly two hours. Attacks occur both daytime and nighttime in most cases. Chronic paroxysmal hemicrania occurs on the same side in greater than 95% of patients. Chronic paroxysmal hemicrania differs from episodic paroxysmal hemicrania in that no remission or remission lasts less than three months. Paroxysmal hemicrania responds well to indomethacin (an NSAID), with complete resolution in most patients.”

A brief understanding of cluster headaches source: Trigeminal autonomic cephalgia

In your medical journey, you may have had it explained to you that your headaches fall under a diagnosis of Trigeminal autonomic cephalgia. Cephalgia means cluster headaches. Simply, and as you are well aware, your headaches typically seem to be generated on one side of your face, centralized behind your eye. That eyelid may droop, you may have tearing or redness in that eye, and/or your nose may clog. These symptoms occur on one side of your head and are caused by pressure on and traveling the path along the trigeminal nerve.

The key points in the illustration below are simple. As you know, your cluster headache can be a stabbing pain behind an eye or in the temple region.

The illustration below points out that the “nuclei are situated within the CNS and the ganglia are outside of the CNS. What does this actually mean to you? This is a simple explanation:

Why it is important to note that the ganglia is outside of the Central Nervous System is because it can be subjected to nerve compression on its own. Cervical spine instability can cause compression on these nerves that cause pain, loss of sensation, or cluster headaches among a large myriad of symptoms. This nerve compression can also cause confusing and conflicting messages from the Maxillary (V2) and Ophalmic (V1) nerves. Your brain is not getting the right messages and it is responding to "bad information." Your headaches are not only the result of this bad information, but the cause as well.

Why it is important to note that the ganglia is outside of the Central Nervous System is because it can be subjected to nerve compression on its own. Cervical spine instability can cause compression on these nerves that cause pain, loss of sensation, or cluster headaches among a large myriad of symptoms. This nerve compression can also cause confusing and conflicting messages from the Maxillary (V2) and Ophthalmic (V1) nerves. Your brain is not getting the right messages and it is responding to “bad information.” Your headaches are not only the result of this bad information but the cause as well.

The start of the chase for the root cause of the problem. The connection between the vagus nerve and the trigeminal nerve and trigeminal ganglion.

What perhaps isn’t appreciated enough in pain management is the fact that structural abnormalities such as upper cervical instability can cause nerve stimulation to cranial nerves and even blood vessels, causing headaches. As discussed above, the parasympathetic nervous system is generally involved with the vasodilation of blood vessels, and the sympathetic nervous system is generally involved with vasoconstriction. It is now known from clinical and animal data that the observed vasodilation in headaches is, in part, an effect of a trigeminal parasympathetic reflex, which is part of the trigeminovascular system. There is evidence that there is direct trigeminal neural innervation of the cranial circulation.

The pathophysiology of several types of headaches including cluster, paroxysmal hemicranias, and some types of migraines are felt in whole or in part to be due to trigeminal-induced vasodilation of cerebral blood vessels. These neovascular headache syndromes are collectively termed trigeminal autonomic cephalalgia. They often have common features including severe unilateral, commonly retro-orbital pain accompanied by restlessness or agitation as well as cranial (parasympathetic) autonomic symptoms, such as lacrimation (tearing of the eye) or conjunctival injection (redness of the eye). The severe unilateral headaches generally last minutes and attack frequency can range from 5 to 40 attacks per day. The belief is that this reflex trigeminal-autonomic activation causes vasodilation of blood vessels. However, it also causes stimulation of several cranial nerves, including the facial and seventh cranial nerves, which causes autonomic symptoms in the face such as conjunctival injection and lacrimation.

The vagus nerve, as illustrated below, travels through the cervical spine. It travels especially close to the C1, C2, C3 vertebrae. Cervical spine instability in these regions can cause herniation or pinching of the vagus nerve, which can lead to a disruption of normal nerve communication between the vagus nerve, the trigeminal nerve, and the trigeminal ganglion. This disruption or herniation of the nerve can cause among the many symptoms of cluster headaches.

The vagus nerve, as illustrated here, travels through the cervical spine. It travels especially close to the C1, C2, C3 vertabrae. Cervical spine instability in this regions can cause herniation or pinching of the vagus nerve, which can lead to a disruption of normal nerve communication between the vagus nerve and the trigeminal nerve and trigeminal ganlia. This disruption or herniation of the nerve can cause among the many symptoms  cluster headaches.

The vagus nerve, as illustrated here, travels through the cervical spine. It travels especially close to the C1, C2, C3 vertebrae. Cervical spine instability in these regions can cause herniation or pinching of the vagus nerve, which can lead to a disruption of normal nerve communication between the vagus nerve, the trigeminal nerve, and the trigeminal ganglia. This disruption or herniation of the nerve can cause among the many symptoms of cluster headaches.


An understanding of the interplay between the vagus nerve and the trigeminal nerve

In the medical journal Cephalalgia, (3) February 2019, researchers at Radboud University Medical Center in the Netherlands focused their attention on the vagus nerve for non-invasive stimulation in headache relief. They noted that the vagus nerve is thought to modulate the headache pain pathways in the brain.

The study showed that non-invasive stimulation of the vagus nerve in primary headache disorders is moderately effective, safe, and well-tolerated.
The study also showed a deep and intricate entanglement between fibers of the vagus nerve and the trigeminal nerve.

Among their findings, the one that we want to illustrate is what the researchers suggest in their conclusion: “The moderate effectiveness of non-invasive stimulation of the vagus nerve in treating primary headache disorders can possibly be linked to the connections between the trigeminal and vagal systems.”

What we would like to point out here is that problems of cluster headaches as they relate to cervical neck instability, do not usually sit in isolation. It is usually a combination of problems that lead to difficult-to-treat or unresponsive cluster headaches. In this case the vagus and the trigeminal nerves.

In this illustration a close up view of the C1, C2, C3 proximity to the Trigeminal cervical nucleus and the Trigeminal nerve afferents, Maxillary (V2) and Ophalmic (V1). Cluster headache origins in the cervical spine make a lot more sense when you see the nerves of the cervical spine and their close interplay.

In this illustration a close-up view of the C1, C2, and C3 proximity to the Trigeminal cervical nucleus and the Trigeminal nerve afferents, Maxillary (V2) and Ophthalmic (V1). Cluster headache origins in the cervical spine make a lot more sense when you see the nerves of the cervical spine and their close interplay.

Chasing the Trigeminal autonomic cephalalgia diagnosis

According to the National Institute of Neurological Disorders and Stroke: Trigeminal autonomic cephalalgias are primary headaches that include cluster headaches, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing or cranial autonomic features.

Let’s briefly explain all of this.

Going back to the National Institute of Neurological Disorders and Stroke guidelines on treatment:

More clues that your problem may be caused by cervical neck instability

It is likely that if you are researching cluster headaches, Indomethacin did not offer you complete relief. The recommendation that paroxysmal hemicrania and trigeminal neuralgia should be treated independently of each other is another clue that the problem may be in the neck. How? Because the medications needed for each disorder will not be effective for the other disorder. Therefore the medications are not treating a “common source of pain origin.”  This may be the pressure on the nerves caused by cervical neck instability. This is something we see frequently in concurrent headache and head pain disorders where cervical neck instability is identified.

Chasing another diagnosis: Is it Trigeminal neuralgia (nerve pain) or hemicrania continua (cluster headaches)?

Trigeminal neuralgia or nerve pain centers on what is happening to the trigeminal nerve which carries pain, feeling, and sensation from the brain to the skin of the face. In the case of trigeminal neuralgia, most medical professionals cannot find the cause of why this pain started. This is borne out by the definition of trigeminal neuralgia.

Doctors are trying to treat a condition that they do not know what the cause is.

The missing or delayed diagnosis – why it took years to figure out what is causing your headaches and why it may still be the wrong diagnosis

A June 2019 study in the Journal of Headache Pain (4) led by King’s College London assessed headache disorders in patients coming into very specialized orofacial pain clinics after dental causes were ruled out. Of the one hundred and forty-two patients reviewed; there were 100 women (70%) and 42 men (30%).

The researchers also noted these findings on diagnosis prior to coming to the clinic

Delay to diagnosis

More symptoms that may reveal a true diagnosis. 

A January 2022 paper in the Journal of Headache Pain (5) suggests “Voice change and throat swelling should be recognized as possible parasympathetically-mediated Cranial autonomic symptoms.”We will discuss this further below.

Vagus Nerve and trigeminal nerve stimulation with Non-invasive neuromodulation when medical treatment is contraindicated

In this section we will look at various treatment options we will look at:

An August 2023 paper in the Cephalalgia: An International Journal of Headache (6) writes: “Acute treatments for cluster headache are primarily delivered via rapid, non-oral routes (such as inhalation, nasal, or subcutaneous) while preventives include a variety of unrelated treatments such as corticosteroids, verapamil, and galcanezumab.

Neuromodulation is becoming an increasingly popular option, both non-invasively such as vagus nerve stimulation when medical treatment is contraindicated or side effects are intolerable, and invasively such as occipital nerve stimulation when medical treatment is ineffective”

Below we will discuss vagus nerve stimulation especially when medical treatment is contraindicated.

Because of the limited effect of pharmacological medications on cluster headaches, researchers are exploring neuromodulation or direct electrical stimulation on the vagus and trigeminal nerves

Neuromodulation may have been offered to you for your headache pain. This is the use of electric current to alter or modulate pain impulses. Non-invasive neuromodulation is where the electric stimulus remains outside of the body and is not implanted in the body.

A June 2023 study in the journal Scientific Reports (7) “suggested that migraine patients without aura have altered brain connectivity patterns in several hub regions involving multisensory integration, pain perception, and cognitive function. More importantly, Transcutaneous auricular vagus nerve stimulation modulated the default mode network and the vestibular cortical network related to the dysfunctions in migraineurs.” The research further suggests “Transcutaneous auricular vagus nerve stimulation shows excellent effects on relieving clinical symptoms in migraine patients.”

A March 2019 study led by German researchers and published in the Journal of Neurology, Neurosurgery, and Psychiatry (8) wrote:

In other words, research is limited, but the treatment may help.

In December 2018 The FDA approved a twice-daily self-administered treatment that provides patients with 3 consecutive two-minute electrical stimulations through the skin of the neck that activates the vagus nerve to provide relief. In The Journal of Headache and Pain (9), in December 2017 migraine and headache specialists in Germany found that patients receiving stimulation to the Vagus nerve and standard-of-care medications reduced cluster headache attacks significantly more than with standard care alone in a four-week trial.

In June 2020, in the journal, Current Opinion in Neurology (10) researchers at King’s College London wrote: “Neuromodulation strategies aimed at anatomical structures involved in the pathophysiology of cluster headaches, such as the sphenopalatine ganglion (associated with the trigeminal nerve) and the vagus nerve, have proved effective in reducing the pain intensity and the number of attacks, and also to be safe and well-tolerated.”

While we do not use neuromodulation strategies, we do agree that addressing the pathophysiology of cluster headaches, such as the sphenopalatine ganglion (associated with the trigeminal nerve) and the vagus nerve is a path that needs to be explored.

A December 2023 paper in the journal Current Opinion in Neurology (11) looked at vagal nerve stimulation for headaches. The researchers write: “Vagal nerve stimulation (VNS) is emerging as a probable therapeutic option for headache. Several questions remain on the mechanism of action, device parameters, efficacy, duration of treatment, and long-term safety.”

Of course, vagal nerve stimulation is not without its controversies. In this study, the doctors reviewed recent findings for vagal nerve stimulation in alleviating headache symptoms in patients and offered their findings. Among the problems, the doctors wrote about that while potential biomarkers of headache (an example of a biomarker is the calcitonin gene-related peptide (CGRP), a 2014 paper wrote (12): “CGRP is a highly potent vasodilator and, partly as a consequence, possesses protective mechanisms that are important for physiological and pathological conditions involving the cardiovascular system and wound healing. CGRP is primarily released from sensory nerves and thus is implicated in pain pathways” These have been linked to acute migraine attacks).

The 2023 examined the biomarker effect and possible treatment effects. In support they noted was a “study on post-COVID-19 headache and its management with noninvasive cervical VNS adds to the body of original studies.” However, they also note: “The collection of these studies adds some data to mechanisms of VNS without adding much insight to differential effects of sub-types of VNS and possible device settings that could prove to be beneficial for headache management.” In other words, there are no standard protocols.

A September 2023 systematic review published in the Journal of Clinical Medicine (13) found moderate-to-high-quality evidence supporting that non-invasive neuromodulation of the vagus nerve and cervical neuromodulation of the vagus nerve may have some positive effects at the end of the treatment being effective to relieve the frequency and intensity of cluster headaches. The poor quantity of studies available and the lack of homogeneity in the study protocols did not allow the pooling of data for a meta-analysis. (In other words, comparisons and outcomes could not be accurately obtained.)

In June 2023, researchers writing in the Frontiers in Neuroscience (14) found “Some positive effects regarding the effect of non-invasive neuromodulation, auricular transcutaneous vagus nerve stimulation (at-VNS), and electro-ear acupuncture of the vagus nerve on migraine is reported in the current literature, but there are not enough data to obtain strong conclusions.”

Suprazygomatic pterygopalatine ganglion blocks and non-invasive vagus nerve stimulation

A November 2023 review of patient cases published in the Regional anesthesia and pain medicine (15) writes of nine patients with 11 longstanding treatment-refractory primary headache disorders and epidural blood patch (typically given to stop  cerebrospinal fluid leaks–resistant post-dural puncture headache (PDPH) received ultrasound-guided percutaneous suprazygomatic pterygopalatine ganglion blocks ((PPGB) from a 2022 study  (16) “Pterygopalatine fossa blocks have been demonstrated to be of value for multiple conditions, including migraines, post–dural puncture headaches, headaches associated with intracranial bleeding, and perioperative analgesia for operations in the mid-face, nose, paranasal sinuses, palate, and proximal pharynx, as well as multiple idiopathic and complex facial pain syndromes.”)). In this review of patients, seven also received non-invasive vagus nerve stimulation (nVNS). the rproting doctors wrote: “(The patients) experienced dramatic, immediate, satisfactory, and apparently lasting symptom resolution (at the time of the writing of this report).”

Surgical techniques include the implantation of deep brain or peripheral nerve electrodes

In March 2019, neurosurgeons in Italy offered a summary of surgical techniques in the journal Neurological Sciences (17) and what they may be offered to patients for:

Implantation of deep brain or peripheral nerve electrodes with subsequent chronic stimulation

Above we spoke about non-invasive neuromodulation. Here we will examine INVASIVE neuromodulation with the help of University of Minnesota researchers who published these observations in the journal Pain Research and Treatment. (18)

Here are the learning points:

Some people are helped by the surgical implant of stimulation devices. Some people are not.

A June 2022 paper from researchers at the Department of Neurosurgery, Humanitas Research Hospital in Italy, published in the Neurosurgical review (19) suggested that when cluster headache does not respond to medical treatment, it can be treated with Gamma Knife radiosurgery (GKRS). However, the outcomes of studies investigating Gamma Knife radiosurgery (GKRS) for cluster headaches in the literature are inconsistent, and the ideal target and treatment parameters remain unclear.

The researchers reviewed the data of five previously published studies describing outcomes of Gamma Knife radiosurgery for the treatment of cluster headaches for a total of 52 patients (48 included in the outcome analysis).

Nerve compression surgery and non-surgical nerve compression options


Prolotherapy for headache

In 1993, Caring Medical opened its doors, and among our first patients were people who suffered from chronic headaches. Sixteen years later we were able to document our experience in treating patients with headaches with Prolotherapy injections:

In 2009, we published research in the journal Practical Pain Management (20) that showed weak or loose neck ligaments and/or tendons may act as headache triggers because of the instability they create in the neck. Instability leads to hyper vertebrae motion and compression of nerves and arteries that may restrict blood flow into the brain.

Our findings strongly suggest that Prolotherapy injections can play a role in decreasing intensity level, frequency, duration, number of associated symptoms, and light sensitivity in patients with headache and migraine pain.

Throughout this article, we have made references to cervical neck instability causing pressure on the vagus and trigeminal nerves and the various treatment options offered to help remedy this situation. Some treatments work, some do not. We have illustrated these points above.

In our examination, we too are looking for compression.

In this video, DMX displays Prolotherapy before and after treatments that resolved problems of a pinched nerve in the cervical spine


The head and neck, like all parts of the body, live in a complex relationship. Something in the neck can cause problems in the jaw, face, shoulders, fingers, etc. Problems in the jaw can cause problems in the neck. Any musculoskeletal problem can cause problems of headaches. Back to the keyword “compression.” We are looking for problems in the neck that can be influencing problems of the head and jaw.

Common characteristics of cervical neck instability causing headaches 

In our patient interviews at our first meeting, we find that people with cluster-type headaches:

In this video, a demonstration of treatment is given

Prolotherapy is referred to as a regenerative injection technique (RIT) because it is based on the premise that the regenerative healing process can rebuild and repair damaged soft tissue structures. It is a simple injection treatment that addresses very complex issues.

This video jumps to 1:05 where the actual treatment begins.

This patient is having C1-C2 areas treated. Ross Hauser, MD, is giving the injections.

Cluster headaches are an extremely challenging problem. We have presented our case that Prolotherapy injections can be a viable option in stabilizing cervical neck instability and its possible cause of pressure on the vagus and trigeminal nerve.

Summary

For the person with signs and symptoms of cervical instability including muscle tightness in the neck, crepitation sensations in the neck with rotatory motions, suboccipital headache, migraines who also have noticed changes in speech, voice quality, taste or swallowing, or symptoms such as tachycardia, whole body allodynia (sensitivity to touch), hyperalgesia (exaggerated pain response) or conditions such as dysautonomias, comprehensive prolotherapy may offer one solution to the resolution of symptoms.

Equally, in most cases of vagus nerve dysfunction seen at Caring Medical, there is obvious neck injury causing cervical instability so this is where treatment is addressed by comprehensive Prolotherapy. When motion x-ray demonstrates significant upper cervical instability, Comprehensive Prolotherapy is done to the C1-C2 region, often under fluoroscopic guidance. Generally, within a few visits, the person’s neck and headache symptoms are drastically improved, along with the systemic symptoms from vagus nerve dysfunction. There are times when despite improvement with Prolotherapy, the person still has some symptoms, and possibly nerve regeneration is needed.

If this article has helped you understand the problems of cluster headaches and you would like to explore Prolotherapy as a possible remedy, ask for help and information from our specialists

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This article was update January 1, 2024

 

 

 

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