SUMOylation and DeSUMOylation: Tug of War of Pain Signaling.

SUMOylation is a post-translational modification that attaches a small ubiquitin-like modifier (SUMO) group to a target protein via SUMO ligases, while deSUMOylation refers to the removal of this SUMO group by sentrin-specific proteases (SENPs). Although the functions of these processes have been well described in the nucleus, the role of SUMOylation and deSUMOylation in regulating ion channels is emerging as a novel area of study. Despite this, their contributions to pain signaling remain less clear. Therefore, this review consolidates the current evidence on the link(s) between SUMOylation, deSUMOylation, and pain, with a specific focus on ion channels expressed in the sensory system. Additionally, we explore the role of SUMOylation in the expression and function of kinases, vesicle proteins, and transcription factors, which result in the modulation of certain ion channels contributing to pain. Altogether, this review aims to highlight the relationship between SUMOylation and deSUMOylation in the modulation of ion channels, ultimately exploring the potential therapeutic role of these processes in chronic pain.