The potential of microfluidic platforms for neuron differentiation and pain modeling in novel drug discovery

Traditional cell culture assays and animal models have dominated early-stage drug discovery for neurological disorders and pain. However, the development of new analgesic drugs has long been hampered by the complexity of pain pathways and, the poor translational fidelity of existing in vitro systems. These models often fail to translate to human based interventions contributing to high attrition rates of candidate analgesic compounds in clinical trials. Chronic pain, particularly neuropathic pain, involves intricate neuroimmune interactions and synaptic plasticity that are not fully recapitulated in conventional cell culture or animal models. In recent years, microfluidic platforms advanced into transformative, human-relevant models that bridge the gap between traditional assays and in vitro systems. Their precise control over the cellular microenvironment, spatial organization, and scalability are all fundamental capabilities that support on-chip neuronal differentiation and enable the investigation of complex neuronal circuitry involved in the development of chronic pain. Here we provide our perspective on how advancements in microfluidic technologies contribute to understanding pain mechanisms, accelerating analgesic drug discovery and personalized pain therapeutics.