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.

Chronic Neuropathic Pain is frequently associated with peripheral nerve injury or disease. Peripheral injury activates both neuronal and glial components of the peripheral and central cellular circuitry. While it is widely known that the subsequently altered interactions between neurons and glial cells contribute to pain development and to its chronification, the underlying mechanisms are poorly understood. Developing mechanism-based therapies targeting neuron-glial interactions to treat chronic pain will be crucial for improving the quality of life of many patients. Hence the development of novel therapeutic solutions represents a major challenge that demands a multi-disciplinary approach to decipher and understand pathological mechanisms and to translate them into predictive tools for drug development. The NGN-PET consortium addresses this challenge by forming a highly interdisciplinary team that builds upon expertise in areas of academic research on pain mechanisms, industrial knowhow on human stem cell-based tool development, HTS technologies and drug discovery. To achieve its goal we will develop preclinical model systems and assays which recapitulate the human in vivo situation and which can be interrogated for the identification, validation of molecular targets and the development new treatments. A focus of the project will be chemotherapy induced NP and the interplay between nociceptors, microglia and Schwann cells. NGN-PET will carefully characterize rodent in vivo and in vitro models to identify these mechanisms, and will develop rat and human iPSCs based in vitro systems of neuron-glial co-cultures that can be interrogated for targets and used for compound identification and validation. NGN-PET will thus pose the basis for the translation of these model systems into high throughput screening platforms for pharmaceutical research and drug discovery.