The inflammation of the organism, certain changes in genetic regulation, and exposure to compounds present in tobacco smoke could be implicated in the development of cluster headaches, according to two recent works from the Karolinska Institute (Sweden).
Cluster headache is an unusual neurological disorder that manifests with sudden attacks of extremely intense headache pain. Due to the severity of the pain, it is sometimes referred to as "suicidal headache," and its underlying causes remain largely unknown.
In these two investigations, the team from the Karolinska Institute examined both genetic and environmental factors that could intervene in the onset of cluster headaches.
Genetic analysis and the role of the immune system
In the first of the studies, scientists reviewed genetic risk factors already described in previous genome-wide association studies (GWAS), in which the complete genome of individuals with and without the pathology is compared.
The work included genetic analyses of more than 1,500 participants, as well as molecular studies on blood samples, skin cells, and DNA from smaller subgroups of patients and healthy controls. The findings have been published in the journal "The Journal of Headache and Pain."
The research group confirmed the importance of seven genes previously linked to cluster headaches and found that several of them show different expression in those suffering from this disorder. Six of the seven genes are active in immune system cells or related to the body's inflammatory signaling pathways.
"This reinforces the hypothesis that the immune system and inflammation may play a central role in cluster headaches. Several of these genes influence the same biological signaling pathways, which provides us with important clues about the mechanisms behind the disease," explained Caroline Ran, associate professor at the Cluster Headache Center of the Department of Neuroscience at the Karolinska Institute.
Impact of tobacco smoke and heavy metals
The second work, published in the journal "Cephalalgia," analyzed whether exposure to components of tobacco smoke modifies the regulation of genes in people with cluster headaches. Previous research had already observed that those suffering from this disorder smoke more frequently than the general population.
To this end, blood, DNA, and cerebrospinal fluid samples from patients and healthy individuals who acted as a control group were studied. The number of participants varied between 26 and 79, depending on the type of analysis performed.
Patients with cluster headaches presented markers compatible with greater exposure to heavy metals and other substances derived from tobacco smoke. In addition, they showed alterations in markers that regulate DNA methylation, a process that conditions the activity level of different genes.
"This study cannot demonstrate a cause-and-effect relationship, but the results suggest that environmental factors, such as heavy metals present in tobacco smoke, may interact with biological mechanisms related to cluster headaches," says Andrea Carmine Belin, associate professor at the Cluster Headache Center of the Department of Neuroscience at the Karolinska Institute.
The authors emphasize that both investigations have limitations. The biological analyses were carried out in relatively small groups and several of the results will need to be verified in studies with a larger number of participants.