The four causes of primary headaches

Learn the clinical characteristics of primary headaches and the complex mechanisms that cause them.
Last update14th Mar 2023

Early hypotheses of headache pain focused on peripheral mechanisms. These include extracranial muscle contraction, and vascular dilation in the dura mater and other structures of the head and neck. We now know that these structures can have specific pathologies which may result in a secondary headache, but they are unlikely to be the cause of primary headache disorders. The primary headache disorders have a much more complex etiology and mechanism.

The neurovascular connection and its role in primary headaches

The trigeminal nerve, or fifth cranial nerve, transmits sensory information from the head, face, and dura within the skull. The anterior structures of the head, particularly the face, are innervated by the three divisions of the nerve—ophthalmic division, mandibular division, and maxillary division. The three divisions of the trigeminal nerve are reviewed in more detail in the Medmastery Clinical Neurology Essentials course.

Posterior portions of the head and neck are innervated by upper cervical nerves which are near the trigeminal nerve nucleus caudalis and extend into the upper spinal cord.

Figure 1. The trigeminal nerve innervates the anterior face and head while the nearby upper cervical nerves innervate the posterior portion of the head.

The trigeminal nerve has projections that can release neuropeptides peripherally which contribute to peripheral sensory activation and result in dilation of blood vessels and inflammation in the cranial structures.

Figure 2. Neuropeptides released from the trigeminal nerve cause vasodilation and inflammation in nearby cranial structures.

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Nociception and its relationship to primary headaches

The pain of primary headaches results from activating meningeal nociceptors and other pain receptors in the muscle, skin, and blood vessels throughout the head. This process is enhanced by alterations in normal pain modulation. Neurons that would normally suppress pain activation become less active, while neurons that enhance pain become more active.

Many neurotransmitter substances are involved, including substance P, calcitonin gene-related peptide, and neurokinins. The release of these substances is believed to lead to neurogenic inflammation of vessels and nerve fibers, and thus enhancement of pain.

Figure 3. The pain of headache is caused by substance P, peptides and neurokinins which activate nociceptors in meninges, muscles, skin, and blood vessels in the head leading to inflammation of nerve fibers and blood vessels.

Allodynia and migraine headaches

In migraine, pain perceived from normally non-noxious stimuli, or allodynia, becomes the norm. So activity with minimal movement as well as pulsation of blood vessels and cerebrospinal fluid will cause pain. Abnormalities in peripheral tissues of the head and / or neck can further contribute to pain.

Figure 4. Pulsation of blood vessels or cerebrospinal fluid can cause migraines.

Headaches can manifest in other parts of the body


Migraine and the other primary headaches will sometimes cause pain in other regions such as the sinuses or the posterior head. Neck pain is common in migraine, as is occipital region pain.

Irritation of the occipital nerve, though rare, can cause posterior head pain.

Photosensitivity, phonosensitivity, aura, and other complex phenomena

Complex phenomena, such as photosensitivity and phonosensitivity, which are seen in migraine, can't be explained by simple peripheral vascular mechanisms. Aura, and the influence of stress, weather and hormones are further examples of much more complex phenomena. The pathophysiology of auras involves a spreading cortical region of decreased blood flow and depolarization. These phenomena are under investigation and have led to new theories as to the origin of migraine pain, as well as new approaches to treatment.

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Recommended reading

  • Ferguson, LW and Gerwin, R. 2005. Clinical Mastery in the Treatment of Myofascial Pain. Baltimore: Lippincott Williams & Wilkins.
  • Fernández-De-Las-Peñas, C, Arendt-Nielsen, L, and Gerwin, R. 2010. Tension-Type and Cervicogenic Headache—Pathophysiology, Diagnosis and Management. Boston: Jones and Bartlett.
  • Goadsby, PJ and Silberstein, SD. 1997. Headache. Vol 17 of Blue books of practical neurology. Boston: Butterworth-Heinemann.
  • Goadsby, PJ, Silberstein, SD, and Dodick, DW. 2005. Chronic Daily Headache for Clinicians. Hamilton: BC Decker.
  • Silberstein, SD, Lipton, RB, and Goadsby, PJ. 2002. Headache in Clinical Practice. 2nd edition. London: Martin Dunitz.
  • Ward, TN. 2012. Migraine Diagnosis and Pathophysiology. Continuum (Minneap Minn). 18: 757–763. PMID: 22868539

About the author

Robert Coni, DO EdS
Robert is Neurohospitalist, Medical Director, and Coordinator at the Grand Strand Medical Center, and Clinical Assistant Professor at the University of South Carolina.
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