Resolution and recovery from neuropathic pain are active processes depending, e.g., on resolution of inflammation and restoration of neural circuits in the nervous system. Pain from a nerve lesion may resolve before or without complete anatomical and physiological recovery. If this self-healing process is disrupted, chronic pain may occur, as in chronic postsurgical pain.
Molecular processes of nociceptors
The aim of ResolvePAIN is to better understand molecular mechanisms of pain resolution in peripheral nociceptors as well as their regulation by the CNS. This is achieved by a combined translational approach based on clinical, preclinical, and basic sciences. Questions arising from preclinical animal models or from the empirical clinical experience with patients go hand in hand.
Data analysis from longitudinal studies
Clinical diseases studied in ResolvePAIN are characterized by common characteristics of self-healing and recovery in some patients but not in others. Long-term observational studies of neuropathic pain conditions of different etiologies – i.e., after surgery, trauma, chemotherapy, in autoimmune or genetic diseases – will document in depth phenotypic and histochemical characteristics. The former include innovative imaging methods such as MR neurography, while the latter are obtained from skin and blood sample analyses. Data will be uniformly collected in a new database and can then be analysed for biomarkers with the help of computer-based large data analysis programmes.
Neuropathy models in comparison
Three preclinical models of neuropathic pain – traumatic nerve injury, immunoglobulin transfer neuropathy and nerve damage due to chemotherapy – are employed as a starting point. In parallel, we are investigating molecular patterns of pain resolution in cell cultures of neuronal and non-neuronal systems and in fruit flies. Hypothesis-based and unbiased screening methods are used to characterise the molecular mechanistic networks. These include inflammatory processes, ion channel functions, cell-cell contacts, neurotrophic and neuronal growth factors, oxidised and non-oxidised lipids, genetic and epigenetic mechanisms as well as the influence of the CNS on pain resolution. This will be investigated using social factors on pain perception as an example.
New therapy formats
Understanding recovery from neuropathic pain conditions will help identify subgroups of at-risk patients who require personalised and intensified treatment, as well as potentially new and selective treatment strategies.