Pain-on-a-Chip: A microfluidic device for neuron differentiation and functional discrimination in animal models of chronic pain

Chronic pain is a global health issue that is poorly understood and challenging to treat. Improving pain classification and treatment requires new strategies that objectively discriminate between pain conditions and minimise subjectivity associated with the perception of pain. To address this, we have developed a microfluidic biosensor - termed 'pain-on-a-chip' - that leverages recent advancements in biocompatible microfluidic technology with on-chip differentiation of nociceptor-like cells, enabling small sample volumes to be used. Following neuronal differentiation, we used on-chip live cell Ca²⁺ imaging to functionally validate the system. This includes characterising excitation responses in cells challenged with microfluidic perfusion of known nociceptive stimuli and biological fluids collected from different preclinical pain models. Our results demonstrate that this platform has the potential to discriminate between serum samples from distinct chronic pain models. This system has potential as an objective, and minimally invasive method for distinguishing between different subtypes of chronic pain.