Complex regional pain syndrome working group

Background and own contributions

Complex Regional Pain Syndrome (CRPS) and Chronic Low Back Pain (CLBP) represent two examples of chronic pain conditions. CRPS is a disorder, which typically develops on an extremity following an initiating event such as trauma or surgery (Merskey and Bogduk, 1994). We defined recommendations for a first core outcome measurement set for complex regional pain (Grieve et al., 2017). Clinical manifestations are broad and include sensory, vasomotor, sudomotor, motor and trophic changes. Three major pathophysiological pathways have been identified: aberrant inflammation, vasomotor dysfunction, and maladaptive neuroplasticity (Marinus et al., 2011).

A fundamental challenge for improving lives of CLBP patients is that pain can perpetuate and worsen because of dynamic interactions among several patient-specific factors. CLBP patients with vertebral bone marrow lesions known as Modic type 1 changes (MC1) are a CLBP subpopulation with defined peripheral pain contribution (Saukkonen et al., 2020). MC1 pain relates to sprouting of sensory fibers, overexpression of neurotrophic receptors, and local inflammation (Dudli et al., 2017; Ohtori et al., 2006).

Main hypothesis / research question

The overarching goal is to link pain phenotypes in CRPS and CLBP to pathophysiology and patient outcomes and to identify biomarkers that correlate with pain phenotypes and predict patient outcome. With a rigorous investigation of individual biopsychophysical factors and their interactions, we aim to identify principal factors and interactions that govern patient phenotype and outcome.

We hypothesize that pain phenotypes in CRPS and MC1 relate to the characteristics of the local inflammatory processes and their interaction with resident mesenchymal and immune cells. We aim to identify the molecular inflammatory pain mechanisms in CRPS and MC1, to identify disease-relevant signaling pathways, and to test the efficacy of therapeutics targeting these pathways. We use single-cell and bulk RNA sequencing to identify disease relevant cell populations and pathways, immunohistochemistry to spatially map the relevant populations to pathological tissue alterations, and in-vitro disease models to investigate the molecular pathomechanisms and to test the efficacy of therapeutics targeting these mechanisms.