The Role of Alpha-7 Nicotinic Acetylcholine Receptors in Pain: Potential Therapeutic Implications

Abstract

Abstract: Chronic pain represents a prevalent and costly medical challenge globally. Nicotinic acetyl- choline receptors (nAChRs), one type of ligand-gated ion channels found extensively in both the cen- tral and peripheral nervous systems, have emerged as promising therapeutic targets for chronic pain. Although there are currently no FDA-approved analgesics specifically targeting nAChRs, accumulat- ing preclinical and clinical evidence suggest that selective ligands for alpha 7 (α7) nAChRs show po- tential for treating chronic pain, boasting a reduced incidence of side effects compared with other nico- tinic receptor types. The recent structural resolution of human α7 nAChRs has confirmed their nega- tive association with heightened pain, providing a valuable foundation for the development of targeted medications. This review presents a comprehensive overview, encompassing insights into the roles of α7 nAChRs derived from structural and functional studies, recent advancements in pharmacology, and investigations into their involvement in the pathophysiology of chronic pain. Moreover, the review addresses the variability in analgesic effects based on the type of receptor agonist and highlights the current research limitations. As such, this review offers potential therapeutic approaches for the devel- opment of innovative strategies for chronic pain management.