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Headaches: Cluster


An in-depth report on the causes, diagnosis, treatment, and prevention of cluster headaches.


Cluster headaches, like migraines, are likely due to an interaction of abnormalities in the blood vessels and nerves that affect regions in the face.

Abnormalities in the Hypothalamus

Evidence now strongly suggests that abnormalities in the hypothalamus, a complex structure located deep in the brain, may play a major role in cluster headaches. Advanced imaging techniques have revealed that a specific area in the hypothalamus is asymmetrical in these patients and is activated during a cluster headache attack.

The hypothalamus is involved in the regulation of many important chemicals and nerve pathways, including the following:

  • Nerve clusters that regulate the body's biologic rhythms (its circadian rhythms).
Click the icon to see an image of the hypothalamus.
  • Serotonin and norepinephrine. These are neurotransmitters (chemical messengers in the brain) that are involved with well being and appetite.
  • Cortisol (stress hormones).
  • Melatonin (a hormone related to the body's response to light and dark).
  • Beta-endorphins (substances that modulate pain).

Circadian Abnormalities. Cluster attacks often occur during specific sleep stages. They also often follow the seasonal increase in warmth and light, beginning in summer and ending in the fall. Researchers have therefore focused attention on circadian rhythms, and in particular small clusters of nerves in the hypothalamus that act like biologic clocks.

The most important nervous cluster is the suprachiasmatic nuclei (SCN), which appears to help coordinate the body's activities (sleep/wake) with the environment (dark/light). Some studies support the idea that some failure in this biologic pacemaker may impair the pain control system and cause these terrible attacks.

The hormone melatonin is also involved in the body's biologic rhythms.

Alterations in Serotonin. The brain chemical serotonin is of particular interest in the study of headaches, particularly migraine and cluster headaches. This neurotransmitter (chemical messenger) affects, among other functions, well being, sleep, and appetite. Some research has also suggested that serotonin may play an important role in the way circadian rhythms are expressed. There is some evidence of abnormal regulation of brain serotonin levels in cluster patients (although it is not as pronounced as in migraine patients).

Dilation of Blood Vessels

Cluster headaches are associated with dilation (widening) of blood vessels and inflammation of nerves behind the eye.

Cause of headaches
Cluster headaches may be caused by blood vessel dilation in the eye area. Inflammation of nearby nerves may give rise to the distinctive stabbing, throbbing pain usually felt in one eye. The trigeminal nerves branch off the brainstem behind the eyes and send impulses throughout the cranium and face.

In both cluster and migraine headaches blood vessels dilate, but in cluster headaches only the blood vessels behind the eyes pulsate. What causes these events and how they relate to cluster headaches are still unclear:

  • Because blood vessel dilation appears to follow, not precede, the pain, some action originating in the brain is likely to be part of the primary process.
  • Some experts believe that at least some of the pain is caused by dilation in branches of the carotid artery (a major artery that supplies the brain with blood).
  • Certain substances, such as histamine and a protein called endothelin-1 that widens blood vessels and are being investigated for a possible role in cluster headaches.

Other Factors

Nitric Oxide. Nitric oxide is a small molecular messenger that activates nerve pathways in the brain, muscles, or elsewhere. It may contribute to major primary headaches (tension-type, cluster, and migraines) by specifically triggering inflammation and overactivity in the trigeminal nerves. (This is a major nerve pathway that runs from the brain stem to the head and face.) However, other factors must be present that make cluster headache patients susceptible to the actions of nitric oxide.

Immune Abnormalities. Researchers are also investigating whether over-production of certain immune factors called cytokines may contribute to cluster headaches. Cytokines, such as interleukins, are known to cause inflammation and injury in high amounts. To date, however, there is no evidence that they play any role.

Abnormalities in the Sympathetic Nervous System. Some evidence suggests that abnormalities in the sympathetic (also called autonomic) nervous system may contribute to cluster headaches. This system regulates non-voluntary muscle actions in the body, such as in the heart and blood vessels.


About 90% of people seeking help for headaches have a primary headache. The balance of cases are secondary headaches, caused by an underlying disorder that produces headache as a symptom. More than 300 conditions can cause headaches. Some of the most common are listed below.

Sinus Headaches. Many primary headaches, including migraines, are misdiagnosed as sinus headaches. Sinus headaches can occur in the front of the face, usually around the eyes, across the cheeks, or over the forehead. They are usually mild in the morning and increase during the day and are usually accompanied by fever, runny nose, congestion, and general debilitation. Sinus headaches spread over a larger area of the head than migraines, but it is often difficult to tell them apart, particularly if headache is the only symptom of sinusitis; they even coexist in many cases. Often, the visual changes associated with migraine can rule out sinusitis, but such visual changes do not occur with all migraines. (In rare cases, sinusitis can cause double vision and even vision loss, a sign of very serious infection.) [For more information, seeWell-Connected Report #62, Sinusitis.]

Headaches that Originate in the Neck. Some headaches may be caused by abnormalities of the neck muscles (called cervicogenic headaches). Nerves in the neck converge in the trigeminal nerve, which is the largest nerve in the skull. It originates in the brain stem and supplies sensation to the face. This nerve can generate pain signals to the facial area that the brain may interpret as headache. Pain is usually on one side; even if it affects both sides of the head it is usually more severe on one side. The quality of the headache may be difficult to distinguish from an aching tension headache or a mild migraine without aura. Cervicogenic headaches can result from prolonged poor posture (such as that caused by sitting in front of a computer keyboard or driving daily for long periods), arthritis, injuries of the upper spine, or abnormalities in the cervical spine (the spinal bones in the neck). Whiplash injuries involve the neck and can cause headaches, which, according to a 2001 British study, resolve within three weeks in 85% of patients.

Temporomandibular Joint Disorder (TMJ, also called TMD). Muscle contractions that cause headaches may be a result of temporomandibular joint dysfunction, which is caused by clenching the jaws or grinding the teeth (usually during sleep), or by abnormalities in the jaw joints themselves. The diagnosis is easy if chewing produces pain or if jaw motion is restricted or noisy. TMJ pain can occur in the ear, cheek, temples, neck, or shoulders. This condition often coexists with chronic tension headache.

Glaucoma. Acute glaucoma is caused by increased pressure in the eye and requires immediate medical attention. Throbbing pain may be felt around or behind the eyes or in the forehead. Patients have redness in the eye and may see halos or rings around lights.

Click the icon to see a depiction of glaucoma.
Click the icon to see an image of the slitlamp test.
Click the icon to see an image of the visual field test.

Brain Tumor. Fear of brain tumor is common among people with headaches, but headache is almost never the first or only sign of a tumor. Changes in personality and mental functioning, vomiting, seizures, and other symptoms are more likely to appear first. When the headache does develop, it is often worse early in the morning or may awaken sufferers during the night.

Neuralgia. Neuralgia is pain due to nerve abnormalities, which can occur in the facial area and resemble migraines or sinus headaches.

Hypertension. Although many people attribute headaches to high blood pressure, the weight of evidence suggests that hypertension does not cause head aches. An exception is malignant hypertension, an uncommon medical emergency in which the blood pressure abruptly rises to extreme levels, causing damage to blood vessels in the brain, heart, and kidneys.

Strokes Caused by Blood Clots or Hemorrhages. A blood clot or hemorrhage in the brain leading to a stroke can cause a severe headache, sometimes referred to as a thunderclap headache when it is very sudden and severe. The onset of such a headache, particularly if it is associated with confusion, stupor, or other neurologic symptoms, mandates prompt medical attention.

Epilepsy. Severe headaches that can last 12 hours or longer are very common in epilepsy. Migraine is particularly associated with epilepsy.

Head Injuries. It is obvious that a significant blow to the head will cause pain. In most cases, the pain is similar to tension-type headache and is treated in the same way as the primary headache. Post-injury headaches, however, can reflect serious damage, ranging from skull fractures to internal bleeding, and monitoring is important.

Disorders of the Meninges. The meninges are the membranes covering the brain and the spinal cord. Meningitis, which is an infection or irritation of these membranes, is an uncommon but potentially serious cause of severe headache. Other symptoms include nausea and stiffness or pain in the neck.

Gynecologic Problems. Many clinicians have anecdotally linked gynecologic problems, such as ovarian cysts and menstrual disorders, to chronic headaches, and new data are emerging to support this association.

Temporal (Giant Cell) Arteritis. Certain causes of headaches are unique to the elderly, such as temporal arteritis, also called giant cell arteritis. Inflammation in arteries that carry blood to the head, neck, and sometimes the upper part of the body can cause very severe headaches. The risk for this headache is highest in people over age 70, especially among women, people of European heritage, and patients with polymyalgia rheumatica.

Miscellaneous Causes of Benign Headaches. Rapid consumption of ice cream or other very cold foods or beverages is the most common trigger of sudden headache pain, which may be prevented by warming the food or drink for a few seconds in the front of the mouth before swallowing. Other common benign causes of headache include eyestrain, dental problems, allergies, systemic infections, and caffeine withdrawal. Headaches may be induced by sexual activity or intense physical exertion. Leakage from spinal cord fluid is rare but can cause headaches that may be mistaken for brain tumors.


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