Drug discovery in bone pain has been hampered by 1) a lack of specialized technological platforms; 2) a lack of appropriate animal models; 3) poor understanding of the biology; and 4) by the interdisciplinarity of the subject area. In the BonePainII project, we worked in a complementary, interdisciplinary and innovative manner to address these challenges. The project consisted of three inter-related work packages. In WP1, we developed advanced in vitro platforms (advanced microfluidics and organ-on-chip) and high throughput techniques to investigate the interplay between the sensory neurons and a pathological bone microenvironment. In WP2, we analysed in vivo models of the painful bone disorders fibrous dysplasia, osteoporotic fracture, osteoarthritis and metastatic bone disease from breast cancer. We identified pain-related behaviors, validated models with clinical gold standard drugs and elucidated peripheral and central nociceptive mechanisms. In WP3, we used cutting edge technologies to identify novel molecular targets and cellular mechanisms, which have significant impact on the development and/or maintenance of bone pain in arthritis and in cancer. In conclusion, the BonePainII project has resulted in novel technologies, validated animal models for drug discovery, and identified novel mechanisms underlying bone pain across a range of painful bone diseases and with the potential to lead to new therapeutics for the treatment of bone pain. The knowledge and results generated in BonePainII have been disseminated via scientific publications, presentations at seminars, workshops and conferences, in open symposia, and to the general public via outreach activities.
