Induced Pluripotent Stem Cell-Based Platforms for Cardiac-Related Pain Research: Molecular Mechanisms, Experimental Models, and Therapeutic Applications

Cardiac-related pain, including angina pectoris and pain accompanying myocardial infarction, remains clinically important, and existing treatments are inadequate for some patients. Animal and primary-tissue studies provide important mechanistic evidence, but species differences and limited access to patient-matched human neuro-cardiac tissue constrain translation. This review synthesizes the following separate advances relevant to future human iPSC-based cardiac-pain modeling: molecular mechanisms that may be reconstructed in vitro; platforms ranging from two-dimensional cultures to proposed sensory-innervated three-dimensional and microfluidic systems; and potential applications in target validation, patient-specific modeling, and analgesic screening. We distinguish direct human iPSC evidence from findings obtained in animal, primary-cell, cardiac-only, autonomic-neuron, or non-cardiac pain models. We also discuss maturation, standardization, and regulatory challenges. iPSC technologies may complement existing models and support mechanism-focused, patient-stratified research, but direct validation in human sensory–neuron–cardiac systems remains limited.