The explanation of the mechanism of the vascular pain of the face, one of the most painful headaches, seems to have been found. A revolution in treatment is coming.
The cluster headache is one of the most painful headaches in pain. This disorder, although one-sided, is part of "paroxysmal unilateral headaches". It consists of the brutal appearance of an excruciating pain around the eye, compared to a burn by a burning poker, and which associates with vasomotor signs in the territory of the trigeminal nerve (tears, redness of the conjunctiva, runny nose… ).
The cluster headache can take two forms: episodic or chronic. Most patients have an episodic form consisting of periods of several weeks to several months of headache attacks followed by remission. People suffering from the chronic form have no remission or, if they have a respite, it is less than 3 months a year. They occur by attacks with several seizures a day (up to 8). Current treatments are very inefficient. A better understanding of what triggers these crises could help identify new therapeutic targets and treatments.
In a new study, the perfusion of a neuropeptide called "calcitonin gene-related peptide" (CGRP) triggers cluster headache attacks, demonstrating the pivotal role of this peptide in this orphan disease. Of the 9 patients with an episodic form of cluster headache who were in the attack phase, 8 pains were triggered after CGRP infusions, compared to one after placebo. Of the patients who were out of the attack phase, none of the 9 participants had pain after CGRP or placebo. Seven of the 14 patients with the chronic form had a seizure of their algie after the CGRP infusion, but none after the placebo. This study, which marks a turning point in the understanding of vascular pain of the face, is published in JAMA Neurology.
An orphan disease treatment
Given the duration of acute attacks (15 minutes to 3 hours), oral treatments available are usually too slow to be useful. Oxygen and sumatriptan injection can sometimes be effective in some patients. To prevent completely the appearance of the attacks would be therefore more interesting. However, to date, no specific preventive treatment for cluster headache has been developed.
An injection of corticosteroids into the occipital nerve, with or without local anesthetic, could be useful, as could verapamil, lithium and melatonin. Unfortunately, the proportion of non-responder patients and frequent tolerance problems, and particularly in patients with a chronic episodic form, are high. In addition, a treatment that has been effective once will not necessarily be effective the next time.
The pivotal role of the peptide linked to the calcitonin gene
It was already known that blood levels of the "calcitonin gene-related peptide" were elevated in cases of cluster headaches and could be triggered by a nitroglycerin infusion. At the same time, it has been observed that effective treatment of attacks normalizes CGRP levels in the blood.
This study demonstrates that CGRP infusion can also trigger cluster headache attacks, but only in patients whose disorder is already active. In a rigorous, double-blind, placebo-controlled study, patients with episodic or chronic forms of cluster headache were infused with CGRP or placebo and monitored for 90 minutes. brings all the methodological guarantees.
An experimental study
The fact that cerebral vascular attacks can be triggered by CGRP infusion in patients whose episodic disorder is already active, but not in others, is indicative of the role of the central nervous system (the brain) in appearance of this disease. It is not simply a peripheral trigger with a secondary reflex response of the trigeminal nerve. The frequently circadian nature of the attacks indicates that the posterior hypothalamic region is probably responsible for this central susceptibility to attack. This seems confirmed by data in functional neuroimaging.
The brains of different patients may have differences in the thresholds of onset of an attack, even in those whose disorder is active. For example, in this study, those with a higher natural attack frequency were more likely to be triggered than others.
A new treatment route
Phase III studies have demonstrated the efficacy of anti-CGRP monoclonal antibodies, or their receptors, in the prevention of acute and chronic forms of migraine, and the first of these has just been approved by regulatory authorities in this indication.
Given all the available data and the present study, it is very likely that these drugs may also be useful for the treatment of cluster headache. This is the focus of ongoing studies with monoclonal anti-CGRP antibodies in cluster headache.
We are at the dawn of a therapeutic revolution for patients suffering from one of the most painful diseases.