Chronic pain is a debilitating health condition that afflicts ~1.5 billion people globally. Ion channels expressed in the central and peripheral neurons are indispensable for sensing pain. Calcium-conducting ion channels, including neuronal nicotinic acetylcholine receptors (nAChRs), transient receptor potential (TRPs) and ionotropic glutamate receptors (iGluRs), are strongly implicated in chronic pain perception. We aim to understand the cellular processes underlying pain perception mediated by neuronal nicotinic AChRs and iGluRs and try to develop novel therapeutic drug candidate molecules against these targets by using a combination of patch-clamp electrophysiology, fluorescence-based high-throughput screening (HTS) in cellular, animal, and human tissue models of pain. Our overall goal is to understand the mechanism of chronic pain and aid development of better therapeutics.