The pain experience reflects the interaction of diverse genetic and epigenetic factors, and environmental factors. This complexity necessitates the need to establish more relevant pre-clinical models to investigate sensory neuron physiology and disease pathophysiology, with the intention to inform the development of more effective treatment for pain disorders. This workshop will cover examples of how cell-based experiments are being conducted to understand changes in excitability of sensory neurons are heavily linked to the onset and maintenance of pain. To understand how these changes occur after disease or injury, this workshop will discuss dynamic regulation of axonal trafficking of ion channels that are implicated in nociception. Detailed assessments of human sensory neurons derived from iPSCs are leading to the identification not only of causative mutations, but also being used as pain-in-a-dish cellular models to fill gaps in our understanding of clinical phenotypes, and as cellular models to test effective treatment options. Finally, natural pain-inducing toxins are leading to new discoveries including deorphanizing members of the dispanin family as the first NaV channel-interacting proteins that are indispensable for toxin-mediated effects on NaV channel gating, providing insights into the function of these channels in sensory neurons.