Project Rationale

Scientific Rationale for the Proposed Networking Group

Chronic pain is defined by the International Association for the Study of Pain (IASP) as pain that persists for longer than three months¹, and a new classification of chronic pain within ICD-11 points towards chronic pain as different, distinct disease forms, including primary and secondary pain conditions². Although suffering of patients with chronic pain is obvious and many efforts in pain research have been undertaken, there is a big gap between preclinical and clinical research (i.e., results from animal and human studies) hampering improved pain management and patient stratification for treatment options, as most biomarkers/drug targets identified in preclinical research have not been shown to be relevant for patients³⁴.

There are several reasons for this mismatch: One major problem is the discordance between outcomes assessed in preclinical and clinical studies. Studies in animals use primarily evoked pain assessments, whereas chronic pain patients suffer from ongoing pain, with evoked pain usually being less relevant, and psycho-social aspects are only rarely considered. In addition, rodent studies have primarily focussed on male animals, not reflecting the prevalence of pain in female patients. Furthermore, while multiple preclinical rodent models for several pain-related diseases are increasingly developed, neither criteria nor consensus for the best suitable translational model for a disease has been defined.

Even within clinical (as well as preclinical) studies, comparability is hampered by heterogeneous study protocols, differing measures used to assess outcomes, etc. Finally, many of the proteins, genes and neuronal and inflammatory pathways (*omics) relevant for chronic pain diseases (and possibly serving as treatment targets and for patient stratification) differ between species (e.g., rodent and human); yet parallel studies in rodents and humans enabling identification of similarities and differences between species are only recently elaborated. All this is hampering comparison and translation from preclinical to clinical studies (and vice versa).

Harmonization Efforts

Many consortium members have started to harmonise study protocols for preclinical studies (in the EU-funded Innovative Medicines Initiative (IMI) Pain-Care and the EQIPD consortia), or for clinical studies (MI-PainCare, Dolorisk or IMI-EuroPain), including patient-reported outcome measures (PROMs) for chronic neuropathic, visceral and postsurgical pain, sensory measures (quantitative sensory testing, QST) for neuropathic pain, and others⁵⁷. However, harmonising study design between distinct aetiologies for chronic pain (e.g., chronic postsurgical, neuropathic, visceral, pelvic, and musculoskeletal pain) and between preclinical and clinical trials to better compare data from animals to humans and improve translation of research findings are rare.

Similarly, electronic platforms enabling data comparison from different clinical trials, different preclinical studies, and – in a translational approach - from preclinical to clinical trials are currently missing. Consequently, the comparison across datasets is hampered between proteomic, genomic, and transcriptomic studies in patients and between preclinical and clinical studies, which leads to ineffective use of financial and personal resources (e.g., investigation of targets in rodent models turning out to be non-relevant in human patients) and increased risk of failure in clinical studies.

Network Objectives

Within this network, we will bring together world-leading experts from many different disciplines with great experience in pain management, preclinical and/or clinical pain research, and study design. The areas of expertise include preclinical animal pain research (behavioral readouts and disease-specific models), human- and patient-related pain research, pain trial specialists, disease-specific pain researchers of different disciplines, methodologists for genomics, transcriptomics, proteomics and patient-reported outcome assessment, data scientists, patient representatives, and pain societies, all of which have contributed to large national or international pain research in past consortia.

In the one-year funding period, we will exchange study- and method protocols used in previous (animal and human) studies and consortia. We will determine commonalities and differences in existing outcome parameters, study protocols, and datasets. Further, we will discuss the relevance and practicability/feasibility of data harmonisation, focusing on translational aspects (from animals to humans to patients and back) as well as methodological approaches (e.g., *omics) and consent on a minimum but most meaningful dataset to be assessed. Finally, we will provide a roadmap for exchange and comparison of data sets related to preclinical animal-, clinical- and *omics-data.