Identifying the aetiology of headache pain

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.

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.

neurovascular connection and its role in primary headaches
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.

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 generelated peptide, and neurokinins. The release of these substances is believed to lead to neurogenic inflammation of vessels and nerve fibres, and thus enhancement of pain.

Nociception and its relationship to primary headaches
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 fibres 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.

External manifestation

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.

When there is an identifiable issue in the cervical spine or musculature of the neck such as cervical stenosis, and neck pain can reasonably be attributable to the lesion, you may be seeing cervicogenic headache.

Photosensitivity, phonosensitivity, aura, and other complex phenomena

Complex phenomena, such as photosensitivity, 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.

This is an edited excerpt from the Medmastery course Headache Masterclass by Robert Coni, DO, EdS, FAAN. Acknowledgement and attribution to Medmastery for providing course transcripts.


Neurology Library: The primary headache disorders

Neurology Library

Robert Coni, DO, EdS, FAAN. Vascular neurologist and neurohospitalist and Neurology Subspecialty Coordinator at the Grand Strand Medical Center in South Carolina. Former neuroscience curriculum coordinator at St. Luke’s / Temple Medical School and fellow of the American Academy of Neurology. In my spare time, I like to play guitar and go fly fishing. | Medmastery | Linkedin |

BMBS (The University of Nottingham) BMedSci (The University of Nottingham). Emergency Medicine RMO at Sir Charles Gairdner Hospital Perth, WA. Interested in Medical Education and Emergency Medicine. Swimmer and frequent concert attendee.

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