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Doctoral defence of Adriana Della Pietra, MSc, 1 Dec 2023: The endocannabinoid system offers potential new targets for migraine treatment

The doctoral dissertation in the field of Neuroscience will be examined at the Faculty of Health Sciences at Kuopio campus. The doctoral defence will also be streamed online.

What is the topic of your doctoral research? Why is it important to study the topic?

Migraine is a global challenge, affecting 15% of the population and causing significant disability. Current treatments are often inefficient due to the complexity of migraine mechanisms. In a quest for better solutions, this doctoral research dives deep into the core of migraine pain. It investigates the role of the trigeminal transmembrane mechanosensitive Piezo1 channels in triggering pain and explores how the endocannabinoid system can potentially bring relief. This research offers hope for improved treatment and a brighter future for those fighting migraines.

What are the key findings or observations of your doctoral research?

The findings in this thesis on migraine research reveal the significant role of pro-nociceptive mechanosensitive Piezo1 channels in triggering migraine head pain by activating neurons and glial cells. This research also uncovers the overlapping of the endocannabinoid system with Piezo1 channels expression in pathways responsible for migraine pain signaling. Furthermore, I found that a newly developed compound, AKU-005, efficiently inhibited the main enzymes involved in endocannabinoids degradation, thus offering potential relief from migraine pain. 

These findings have the potential to transform migraine treatment and provide hope for migraine sufferers. This research adds valuable insights to the field, contributing to our understanding of this debilitating condition.

How can the results of your doctoral research be utilised in practice?

The results of this migraine research offer a wealth of practical applications that could revolutionise the treatment of this common disorder. This doctoral research has identified innovative potential targets within the endocannabinoid system, which may lead to new therapies. By focusing on the specific endocannabinoid degrading enzymes MAGL and FAAH, this study holds the promise of developing drugs with fewer side effects, bringing new hope to migraine patients. Moreover, this research paves the way for practical applications in clinical settings, including experiments on human tissues. This project outcome inspires further exploration of endocannabinoid-based treatments in clinical studies. A novel application of the fluorescent dye FM1-43, to monitor and identify the function of Piezo1 channels in specific cell types involved in migraine pain has emerged from this study. In summary, these findings offer new solutions for more effective treatments of migraine pain and suggest an innovative monitoring tool, ultimately improving the quality of care for migraine patients.

What are the key research methods and materials used in your doctoral research?

A multidisciplinary approach was used in this doctoral research, including live calcium imaging to investigate the role of Piezo1 channels in trigeminal neurons and glial cells and innovative chemoproteomic method of Activity-Based Protein Profiling, providing valuable insights into the activities of endocannabinoid degrading enzymes across various regions of the central nervous system linked to migraines. This was complemented by electrophysiological recordings to directly assess action of endocannabinoids on nociceptive spiking in the meninges, where migraine pain originates. Various animal models and tissues were used along with unique human samples available via collaboration with Kuopio University Hospital.

The doctoral dissertation of Adriana Della Pietra, MSc, entitled Pro-nociceptive role of Piezo1 channels and the anti-nociceptive effects of endocannabinoids in the trigeminal system implicated in migraine pain will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Professor Andrew Russo of the University of Iowa, and the Custos will be Professor Rashid Giniatullin of the University of Eastern Finland.

Doctoral defence 



For further information, please contact: 

Adriana Della Pietra, adriana.della.pietra(a), +358405961059,