PainFACT has been executed in overlapping discovery and validation phases with analysis of human and animal data. Key to the discovery phase is the analysis of very large datasets. In humans this encompasses analysis of the clustering of diseases using health registry data for the entire Norwegian population with more than 5M individuals, genetic analysis of large population-based studies, such as UK-Biobank (500k) and Danish Bloodbank (500k), and analysis of blood proteins, brain imaging, and extensive clinical examinations that are available in the Rotterdam Study and Tromsø Study. Importantly this also includes measurements of pain sensitivity – the largest dataset accumulated to date with more 30,000 participants tested. In animal models, a large discovery sample of nearly 300 outbred mice were exposed to either chronic pain or sham treatment with measurement of pain sensitivity, anxiety, depression, memory, metabolic markers, atherosclerosis, brain imaging and gene expression in the brain and spinal cord. Follow-up analysis and validation of findings have been conducted by cross-validation across human cohorts, longitudinal analysis, and more specialized techniques, such as Mendelian randomization studies. A key molecular finding from genetic analysis of pain sensitivity has been tested in animal models where the gene is removed, and resultant effects on pain, comorbid conditions and brain structure and function are observed.
In total the project has held 16 invited presentations at international conferences and published 15 papers, with additional papers submitted or in press. Among these, is a study of the genetics of back-pain (Bjornsdottir, et al. 2022, Nature Communications), identifying 41 genetic variants; and a study identifying the 26 genetic risk loci for fibromyalgia (Kerrebijn, et al., In review). Aside from migraine, the genetics of pain has lagged behind other fields, and getting a grip on the genetics of other common pain outcomes is of central importance for understanding the molecular mechanisms of pain.
Nevertheless, most findings from the study have yet to be disseminated and cannot be shared publicly before they have undergone peer review and publication. Without going into specifics, these findings show that PainFACT has successfully identified novel molecular mechanisms of pain and that these mechanisms also impact comorbid conditions, such as cardiovascular disease, in line with the overall hypothesis of the study.
