Cluster headache treatment – cervical ligament instability and the trigeminal and vagus nerves

Ross Hauser, MD, Caring Medical Florida

Cluster headache treatment – cervical ligament instability and the trigeminal and vagus nerves

If you are reading this article it is very likely that you have been on a long journey trying to find anything that will work for your cluster headaches. If you are like the people that have come to our clinics, your journey has included:

Over the years we have seen many patients, who despite seeing many doctors, could not get help for their headaches. Why? Not all headache treatments work for all headaches. There are some patients that we have seen who had great success with a prescription for Verapamil. For these people, this success started to wane as they approached maximum dosage levels and a new prescription or treatment was necessary.

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 in getting treatment that can help?

A study from Harvard Medical School published March 2019 in The Medical Clinics of North America (1) suggested that most headache patients seeking medical treatments for their headaches 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 that 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 form 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.

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 the one side of your head and are caused by pressure on and travel the path along the trigeminal nerve.

The key points in the illustration 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 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.


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.

The vagus nerve, as illustrated below, travels through the cervical spine. It travels especially close to the C1, C2, C3 vertabrae. 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 and the trigeminal nerve and 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 vertabrae. 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 and the trigeminal nerve and 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, (2) 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, 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.

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 headache, 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. We will discuss this further below.

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 for 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 problems and why it may still be the wrong diagnosis

A June 2019 study in the Journal of Headache Pain (3) lead 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

Cluster headache treatments

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

Cluster headache patients had MORE THAN 12 unique prescription drug claims.
Medication overuse headaches

In the medical journal Headache, (4) researchers looked at the medical history of 7589 patients suffering from cluster headaches. They found:

Most commonly prescribed drug classes for cluster headache patients included:

Only 30.4% of cluster headache patients received recognized cluster headache treatments without opioids during the 12-month post-index period. However, these patients were less likely to visit emergency departments or need hospitalizations (26.8%) as compared to cluster headache patients with no pharmacy claims for recognized cluster headache treatments or opioids (33.6%).

Overuse of medications especially indomethacin, eletriptan and tramadol

In August 2018, headache pain specialists in Italy published these findings in the journal Current Pain and Headache Reports (5):

Here are the points they learned from patients who had failed medication therapy:

People who suffer most are the “worse patients” to get off of medications

Pain medications do help people. They do not help everyone. Some medications can make the situation worse.

In this section, we will briefly provide some research for you on the various medications you have been prescribed or are being recommended to.

Valproic Acid (Valporate)

An October 2016 study in the Journal of Clinical Neurology (6) found that people with a history of hyperlipidemia [including hypertriglyceridemia, hypercholesterolemia, and abnormally level of low-density lipoprotein (LDL) cholesterol] and hay fever and the complication of depression or other psychiatric disorder would not have a positive response to valproate and display a high risk of inconsistent responses to headache prevention treatment surrounded by Valproic Acid usage.

Flunarizine / Sibelium / Propanolol

A December 2018 study in the journal Pain (7) noted that flunarizine is considered a first-line preventative treatment for cluster migraines.

Vitamins and Herbs? Do they help? Is it a Lack of Sunshine?

We are big proponents for the use of nutrition in healing the body but we have to be realistic. Vitamins and diet can help, they may help a lot, they may not help at all.

A July 2018 study in the International Journal of Clinical Practice (8) found that when compared with placebo, melatonin did not reduce the number of daily attacks. The good news was that when people took melatonin, it helped reduce daily painkiller analgesic consumption.

A January 2019 study in the journal Medicine, (9) was a little more optimistic if cautiously so. The researchers found that melatonin is very likely to benefit the prevention of migraines, BUT, it takes three months of consumption of melatonin to see benefits and how much benefit is found is debatable.

In The Journal of Headache and Pain, (10) researchers at Hallym University College of Medicine in Korea suggested that cluster headaches attacks may be related to sunlight and vitamin D metabolism. They wrote: “Vitamin D deficiency is common in patients with cluster headache, but the role of vitamin D deficiency is uncertain, except for its seasonal influence (a lack of sunshine).”

Vagus Nerve and trigeminal nerve stimulation with Non-invasive neuromodulation

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 are not implanted in the body.

A March 2019 study lead by German researchers and published in the Journal of Neurology, Neurosurgery, and Psychiatry (11) 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 (12), 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 attack significantly more than with standard care alone in a four-week trial.

In June 2020, in the journal, Current Opinion in Neurology (13) 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.

Surgery

In March 2019, neurosurgeons in Italy offered a summary of surgical techniques in the journal Neurological Sciences (14) 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.(15)

Here are the learning points:

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

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 (16) that showed weak or loose neck ligaments and/or tendons may act as headache triggers because of the instability they created 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, as 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 headache. 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 their 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.

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

1 Vgontzas A, Rizzoli PB. Nonmigraine Headache and Facial Pain. The Medical clinics of North America. 2019 Mar 28;103(2):235-50. [Google Scholar]
2 Franzini A, Moosa S, D’Ammando A, Bono B, Scheitler-Ring K, Ferroli P, Messina G, Prada F, Franzini A. The neurosurgical treatment of craniofacial pain syndromes: current surgical indications and techniques. Neurological Sciences. 2019 Mar 5:1-0. [Google Scholar]
3 Wei DY, Moreno-Ajona D, Renton T, Goadsby PJ. Trigeminal autonomic cephalalgias presenting in a multidisciplinary tertiary orofacial pain clinic. J Headache Pain. 2019 Jun 11;20(1):69. doi: 10.1186/s10194-019-1019-7. PMID: 31185885; PMCID: PMC6734481. [Google Scholar]
4 Choong CK, Ford JH, Nyhuis AW, Joshi SG, Robinson RL, Aurora SK, Martinez JM. Clinical characteristics and treatment patterns among patients diagnosed with cluster headache in US healthcare claims data. Headache: The Journal of Head and Face Pain. 2017 Oct;57(9):1359-74. [Google Scholar]
5 Grazzi L, Grignani E, D’Amico D, Sansone E, Raggi A. Is Medication Overuse Drug Specific or Not? Data from a Review of Published Literature and from an Original Study on Italian MOH Patients. Current pain and headache reports. 2018 Nov 1;22(11):71. [Google Scholar]
6 Ichikawa M, Katoh H, Kurihara T, Ishii M. Clinical response to valproate in patients with migraine. Journal of Clinical Neurology. 2016 Oct 1;12(4):468-75. [Google Scholar]
7 Stubberud A, Flaaen NM, McCrory DC, Pedersen SA, Linde M. Flunarizine as prophylaxis for episodic migraine: a systematic review with meta-analysis. Pain. 2018 Dec. [Google Scholar]
8 Leite PR, de Oliveira CL, Adriano LF, Luiza CM, Vianna PD, Riera R. Melatonin for preventing primary headache: A systematic review. International journal of clinical practice. 2018 May 24:e13203. [Google Scholar]
9 Long R, Zhu Y, Zhou S. Therapeutic role of melatonin in migraine prophylaxis: A systematic review. Medicine. 2019 Jan 1;98(3):e14099. [Google Scholar]
10 Sohn JH, Chu MK, Park KY, Ahn HY, Cho SJ. Vitamin D deficiency in patients with cluster headache: a preliminary study. The journal of headache and pain. 2018 Dec;19(1):54. [Google Scholar]
11 Reuter U, McClure C, Liebler E, Pozo-Rosich P. Non-invasive neuromodulation for migraine and cluster headache: a systematic review of clinical trials. J Neurol Neurosurg Psychiatry. 2019 Mar 1:jnnp-2018. [Google Scholar]
12 Gaul C, Magis D, Liebler E, Straube A. Effects of non-invasive vagus nerve stimulation on attack frequency over time and expanded response rates in patients with chronic cluster headache: a post hoc analysis of the randomised, controlled PREVA study. The journal of headache and pain. 2017 Dec;18(1):22. [Google Scholar]
13 Villar-Martinez MD, Chan C, Goadsby PJ. Evolving options for the treatment of cluster headache. Current opinion in neurology. 2020 Mar 23. [Google Scholar]
14 Jozef Hendrik Augustinus Henssen D, Derks B, van Doorn M, Verhoogt N, Van Cappellen van Walsum AM, Staats P, Vissers K. Vagus nerve stimulation for primary headache disorders: An anatomical review to explain a clinical phenomenon. Cephalalgia. 2019 Feb 20:0333102419833076. [Google Scholar]
15 Nayak R, Banik RK. Current Innovations in Peripheral Nerve Stimulation. Pain Res Treat. 2018;2018:9091216. Published 2018 Sep 13. doi:10.1155/2018/9091216 [Google Scholar]
16 Hauser R, McCullough H. Dextrose Prolotherapy for recurring headache and migraine pain. Practical Pain Management. 2009:58-65. [Google Scholar]

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