Compared to current pain research, the PAINCAGE Project is the first to tackle the Neuropathic Pain (NP) and Osteoarthritis (OA) problem focusing on the proNGF/NGF-mediated signaling through their interaction with TrkA/p75NTR and sortilin receptors and on the interaction of the NGF system with another crucial player in the pain mechanisms, the Endocannabinoid system. A distinctive and innovative aspect of the PAINCAGE proposal is the analysis at different levels of the pain processing and perception cascade, from periphery to the central cortical areas (Fig. below), thereby studying also the emotional and cognitive aspects involved in NP. From a pharmacological perspective, these studies will lay solid foundations for the development of next-generation drugs targeting the NGF system and for new therapeutical designs, such as the association of (phyto/endo-) cannabinoidand NGF-derived drugs. From a clinical perspective, these studies will allow the identification and validation of new biomarkers to devise ad hoc, patient-selective treatments.
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