Amplification of Glyceryl Trinitrate-Induced Headache Features By Noxious Craniofacial Stimuli in Pain-Free Healthy Humans

Abstract

Aim: Glyceryl trinitrate (GTN) provokes an immediate migraine-like headache, followed by a delayed migraine attack in migraineurs. In healthy volunteers, only an immediate, less severe and shorter headache occurs. The presence of an already sensitized nervous system in migraineurs may underlie the more intense and prolonged GTN-evoked headaches. We tested if in healthy humans, application of noxious cutaneous and/or mechanical stimulation within craniofacial region would enhance or prolong GTN-evoked headache. Materials & methods: Noxious stimuli with a capsaicin patch on forehead, a mechanical headband, or both were applied prior to sublingual GTN (0.5 mg) in 20 healthy volunteers. GTN-induced headache characteristics and sensory responsiveness were recorded. Results: A more intense GTN-evoked headache was produced following application of headband. Conclusion: Noxious mechanical stimulation prior to GTN resulted in a more intense GTN-evoked headache.

Keywords::

• craniofacial
• glyceryl trinitrate
• headache
• pain
• trigeminal system

Acknowledgements

We warmly thank all staff and study participants for their time and dedication. We also appreciate initial inputs from Mette Neumann and Kristina Andersen.

Financial & competing interests disclosure

This study was financially supported by the FSS grant (grant numbers 031301 and 831302) from the Danish Research Council to P Gazerani. Eir (Empowering Industry and Research) at SMI^® also partially supported the students work in this project based on a co-financing plan. The supporting organizations did not have any role in study design, data collection, data analysis and interpretation of data, in the writing of the report, and in the decision to submit the article for publication. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval and have followed the principles outlined in the Declaration of Helsinki for all human experimental investigations. In addition, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was financially supported by the FSS grant (grant numbers 031301 and 831302) from the Danish Research Council to P Gazerani. Eir (Empowering Industry and Research) at SMI^® also partially supported the students work in this project based on a co-financing plan. The supporting organizations did not have any role in study design, data collection, data analysis and interpretation of data, in the writing of the report, and in the decision to submit the article for publication. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.