Project: Chronic pain in Ehlers-Danlos syndrome: clinical and molecular characterization in human patients and a murine model

2019-01-01 – 2022-12-31

Abstract

It is now well established that acute and chronic pain are common, though variable, manifestations
in individuals suffering from Ehlers-Danlos syndrome (EDS). This clinically and genetically
heterogeneous group of heritable connective tissue disorders is characterized by skin fragility, joint
hypermobility and generalized soft 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 activities, quality of life, and psychosocial functioning of EDS patients. 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.
Currently, the nature, natural history and mediators and pathways initiating and maintaining pain in
EDS are virtually unexplored. Therefore, this proposal aims to (1) characterize and document the
natural history of pain in humans with the most common EDS subtypes (classical, vascular and
hypermobile EDS) and (2) assess the role of (aberrant) ECM molecules in the initiation and
generation of EDS-related pain using a murine model for classical EDS. This will be accomplished
through a unique combination of questionnaires and experimental pain testing as well as state-ofthe-
art technologies, equipment, resources and collaborations. The anticipated results of this
proposal will pave the way for future research on EDS-related pain.