Neuropathic pain (NP) is common (population prevalence of 7-8%) and will present a rising health burden in the future. NP results in significant morbidity, reduces quality of life and has a major deleterious impact on health in aging. The reason why some subjects develop neuropathic pain and others do not following the same injury is not known. The exact nature of risk factors for NP and their interaction are currently poorly understood and will be the focus of this project. We will establish an international consortium of leading researchers in the field of NP (DOLORisk consortium) involving members of established academic European consortia studying pain/genomics and neuropathy as well as the SMEs Neuroscience Technologies and Mentis Cura. The project will be highly translational and the starting point will be the study of patients with NP or at risk of developing NP. Specific objectives will be to: 1) Identify the influence of demographic factors, environmental/societal and clinical factors on the risk of developing and maintenance of NP 2) To apply modern genomics to validate (using a targeted approach) and find novel (using genome wide association) genetic risk factors for NP. 3) Use tissue samples and patient derived cells from Biobanks to validate of molecular pathways contributing to chronic pain in patients. 4) To determine if patient stratification using physiological (sensory profile, endogenous analgesic mechanisms and nerve excitability) and psychological factors can predict NP risk and progression. 5) Development of a risk model/algorithm for (severe) NP, combining measurable genetic and environmental factors. Our aim is to understand pain pathophysiology in terms of risk factors and protective mechanisms ranging from molecular pathways to societal impacts. The desired impact is to provide a firm platform to improve diagnosis and stratify patients according to risk profile, employ preventive strategies and ultimately develop novel therapeutics.

There is a very high need for improving the management of pain. Acute and persistent pain of different origins represent a common medical, social, and economic burden, and its pharmacotherapy is often inadequate. To advance management of pain patients and support decision making in clinical practice, more predictive assessments of treatment success are needed. The development of analgesics is onerous because promising preclinical data often do not translate into the clinic. Improved pharmacodynamic biomarkers could define whether nociceptive signalling is adequately modulated by a new drug, so increasing the chance of successful translation and greatly reducing the risk in initiating clinical development. Further, the pathophysiology of chronic pelvic pain indications is poorly understood and no adequate preclinical models are available, precluding focused preclinical research and leaving affected patients with little hope of relief. IMI-PainCare aims at making advances in these three pain areas in a complementary manner. Three subprojects will address specific scientific challenges. Subproject PROMPT will identify Patient Reported Outcome Measures as tools to standardise assessments of treatment success of acute and chronic pain in Real World conditions and controlled trials, and so improve its management; subproject BioPain will validate the translatability of pharmacodynamic biomarkers and PK-PD modelling in pain pathways of healthy subjects and preclinical species, thereby offering tools to improve drug development; subprojectTRiPP will identify biomarkers and novel therapeutic pathways of clinical phenotypes of patients with chronic pelvic pain, which after back-translation, can improve how preclinical models reflecting human diseases. The goal of IMI-PainCare is to improve the care of patients with acute or chronic pain by providing a toolbox to streamline the development process for novel analgesic drugs and to improve treatment quality in clinical practice.

Neuropathic pain affects 5% of the general population and 40% of patients with neurological diseases, and has a key role in the pathophysiology of cancer pain that affects up to 50% of patients in the early disease stage and 30% of survivors, causing an enormous social burden. Treatments are inadequate with less than 50% of patients achieving 50% of pain relief at best, while up to 30% of cancer pain patients experience insufficient analgesia. Signatures of individual susceptibility to pain and analgesic responsiveness are urgently needed to improve patients’ management. Such advances are expected to originate from integrated clinical, basic science and entrepreneurial research readily translating scientific findings into benefits for patients. To consolidate these aims, a new generation of scientists with wide knowledge in neuropathic pain, focused research skills and experience in the interaction with biotechnology companies is needed. The PAIN-Net programme, based on a highly innovative platform of training-through-research and strongly committed to such objectives, will support such talented and inspired early stage researchers. Their research projects, embedded in an advanced molecule-to-man pain network, will contribute to better understanding individual susceptibility to pain and analgesics responsiveness based on next generation sequencing, whole exome sequencing, epigenetics and pharmacogenomics studies, nociceptor and sodium channel functioning based on biophysics and proteomics studies, targeted analgesics based on high-throughput screening, targeted analgesic delivery based on encapsulated cell bioreactor implants, and to the development and extensive characterisation of the first knock-in mouse models of sodium channel-related neuropathic pain based on the CRISP-Cas technology. Most of all, the PAIN-Net programme will offer the unique opportunity to enhance scientific capabilities and prepare to high level academic or private applied research career.