Headache: What's Happening?
Last reviewed: 17.10.2021
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The pathogenesis of headache
The possibilities of pharmacotherapy of headache are still limited due to a lack of understanding of its pathogenesis. It is difficult to verify this or that hypothesis, because the headache is transient, and during the attack, patients often experience severe discomfort and vomiting, which complicates their participation in the study. The creation of an experimental animal headache model also encounters a number of difficulties due to the limited knowledge of the main mechanisms of headache, and also because headache is often only a part of the symptom complex, some components of which can develop 24 hours before the onset of the actual headache . The causes of the headache are exceptionally variable. In some patients, with the help of neuroimaging or other additional methods of examination, it is possible to identify structural or inflammatory changes that are a source of pain. In patients suffering from secondary headache, treatment of the underlying disease often leads to the elimination of a headache. Nevertheless, the vast majority of patients suffer from primary forms of headache, such as migraine or tension headache, in which the physical and additional methods of investigation do not reveal any deviations. Of the various primary forms of headache, the pathogenesis of migraine has been studied most actively. Traditional theories of the pathogenesis of migraine can be divided into two categories.
Vaginal theory
In the late 1930s, Dr. Harold Wolff (N. Wolff) and co-workers found that:
- extracranial vessels during a migraine attack in many patients stretch and pulsate, which can be important in the pathogenesis of headache;
- stimulation of intracranial vessels in the waking patient causes ipsilateral headache;
- vasoconstrictors, for example ergot alkaloids, interrupt the headache, while vasodilators (eg nitrates) trigger an attack.
Based on these observations, Wolff suggested that the narrowing of the intracranial vessels may be responsible for the occurrence of a migraine aura, and the headache results from ricochet expansion and dilatation of cranial vessels and activation of perivascular nociceptive endings.
Neurogenic theory
According to the alternative - neurogenic - theory, the migraine generator is the brain, and the individual sensitivity reflects the threshold characteristic of this organ. Supporters of this theory argue that the vascular changes that occur during a migraine attack is a consequence, not the cause of migraine. They draw attention to the fact that migraine attacks are often accompanied by a number of neurological symptoms, which have either a focal character (aura) or a vegetative nature (prodrome) and which can not be explained by vasoconstriction in the basin of any vessel.
It is possible that none of these hypotheses alone can explain the origin of migraine or other forms of primary headache. Headache, including migraines, is likely to result from the action of many factors (including genetic and acquired ones), some of which are related to the function of the brain, others are associated with blood vessels or circulating biologically active substances. Thus, the researchers reported that a family hemiplegic migraine is caused by a point mutation in the gene that codes for the alpha2 subunit of the calcium channel PQ.
Morphological substrate of headache
Modern ideas about the origin of the headache formed in the last 60 years. Brain shells, shell and cerebral vessels are the main intracranial structures that generate a headache. In the late thirties and forties, studies on awake patients undergoing craniotomy showed that electrical and mechanical stimulation of the blood vessels of the meninges causes an intense piercing one-sided headache. Similar stimulation of the parenchyma of the brain did not cause pain. Small pseudo-unipolar branches of the trigeminal (V cranium) nerve and upper cervical segments innervating the membranes and shell vessels are the main source of the inflow of somatosensory afferentation, which creates a sensation of pain in the head. When these unmyelinated C-fibers are activated, the nociceptive information from the perivascular endings passes through the trigeminal nerve node and is switched through synapses to neurons of the second order in the superficial plate of the caudal nucleus of the trigeminal nerve in the medulla oblongata. These predominantly afferent neurons contain substance P, a peptide associated with the calcitonin gene (Calcitonin Gen-related Peptide - CGRP), neurokinin A and other neurotransmitters in the central and peripheral (i.e., shell) parts of the axons.
The caudal nucleus of the trigeminal nerve also receives afferentation from the rostral nuclei of the trigeminal nerve, the near-conductor gray matter, the large core of the suture, the descending cortical inhibitory systems and is the key link in the regulation of headache. Little is known about the role of central trigeminal projections in the transmission of nociceptive information. Nevertheless, it is believed that second-order neurons in the caudal nucleus of the trigeminal nerve transmit nociceptive information to other stem and subcortical structures, including the more rostral parts of the trogeminal complex, the truncal reticular formation, the parabrachial nuclei, and the cerebellum. From the rostral nuclei, nociceptive information is transmitted to the limbic regions, providing emotional and autonomic responses to pain. Projections are also sent from the caudal nucleus of the trigeminal nerve to the ventrobasal, posterior and medial thalamus. From the ventrobasal thalamus, neurons send axonal projections to the somatosensory cortex, the function of which is to determine the localization and character of the pain. The medial thalamus is projected onto the frontal cortex, which provides an affective response to pain. But, according to available data, the medial thalamus can participate in the transmission of both the affective and the discriminatory components of the pain sensation. Modulation of nociceptive afferentation can occur at one or more levels - from the trigeminal nerve to the cerebral cortex, and each of these levels represents a potential target for the action of medications.