NEW <EM>IN VITRO</EM> AND <EM>EX VIVO</EM> METHODS FOR STUDYING HUMAN DORSAL ROOT GANGLIA

Chronic pain represents a major unmet medical need, affecting millions of patients worldwide and imposing a substantial societal burden. Despite decades of intensive basic research and the identification of numerous candidate targets, very few novel analgesics have successfully translated to the clinic. A key contributor to this translational failure is the reliance on preclinical models that insufficiently capture the complexity and species-specific biology of the human nervous system. In particular, fundamental differences between rodent and human sensory neurons limit the predictive value of commonly used pain models. Human dorsal root ganglia (hDRG) neurons play a central role in pain perception, yet their study is hindered by limited tissue accessibility and by experimental approaches that alter native cellular phenotypes. Here, we present the development of complementary human-relevant platforms to investigate the functional properties of hDRG neurons ex vivo. We established long-term hDRG cultures and organotypic slice preparations that preserve neuronal heterogeneity and key aspects of native tissue organization. Neuronal activity is assessed using electrophysiological recordings and calcium imaging in response to defined stimuli, alongside histological analyses to monitor structural and molecular features over time. In addition, we evaluated a cryogenic preservation strategy that enables long-term storage of viable human sensory tissue while maintaining functional integrity. Together, these approaches provide a physiologically relevant framework for studying human sensory neuron function and support improved translational strategies for pain research.