Chronic pain is one of the most common, yet poorly studied, complaints in patients suffering from Ehlers-Danlos Syndrome (EDS). This heterogeneous group of heritable connective tissue disorders is characterized by skin hyperextensibility and fragility, joint hypermobility and generalized connective tissue fragility and is caused by defects in a variety of extracellular matrix (ECM) molecules. Chronic pain is a major source of disability and has a severe impact on daily functioning. Although pain is a frequent cause for seeking medical help, it is often inadequately controlled by currently used analgesics and represents an unmet medical need.

We recently demonstrated the presence of pain-related behaviour and abnormal dermal innervation in Col5a1+/- mice, a validated model for classical EDS caused by type V collagen defects. This proposal aims to assess the contribution of the abnormal ECM and untangle the specific mechanisms that induce pain and peripheral nervous system changes in this mouse model. Central questions that will be addressed in this proposal are (1) which alterations occur in the peripheral nervous system that generate and propagate pain, (2) how is the ECM altered in EDS and (3) how do these ECM alterations affect the peripheral nervous system?

Our ultimate goal is to translate these results to improve patient management and develop more effective, targeted and safer pain relief for EDS patients and patients with related diseases in the future.