Modeling neuropathic pain in a dish.

The study of pain mechanisms has advanced significantly with the development of innovative in vitro models. This chapter explores those already used in or potentially useful for neuropathic pain research, emphasizing the complementary roles of animal and human cellular models to enhance translational success. Traditional animal models have provided foundational insights into the neurobiology of pain and remain invaluable for understanding complex pain pathways. However, integrating human cellular models addresses the need for better replication of human nociceptors. The chapter details methodologies for culturing rodent and human primary sensory neurons, including isolation and culture techniques, advantages, and limitations. It highlights the application of these models in neuropathic pain research, such as identifying pain-associated receptors and ion channels. Recent advancements in using induced pluripotent stem cell (iPSC)-derived sensory neurons are also discussed. Finally, the chapter explores advanced in vitro models, including 2D co-cultures and 3D organoids, and their implications for studying neuropathic pain. These models offer significant advantages for drug screening and ethical research practices, providing a more accurate representation of human pain pathways and paving the way for innovative therapeutic strategies. Despite challenges such as limited access to viable human tissue and variability between samples, these in vitro models, alongside traditional animal models, are indispensable for advancing our understanding of neuropathic pain and developing effective treatments.