Sigma-2 Receptor/Transmembrane Protein 97 in Pain Modulation: Tracing Historical Roots and Current Research Directions

The sigma-2 receptor/transmembrane protein 97 (σ2R/TMEM97) has emerged as a promising target for treating various diseases, including chronic pain. This review explores the potential of σ2R/TMEM97 as a novel therapeutic target for chronic pain management, addressing the need for effective nonopioid alternatives. First, we provide a historical overview of σ2R/TMEM97 research, tracing its early discovery and investigations. Second, we provide a comprehensive review of current research on the role of σ2R/TMEM97 in pain modulation. Lastly, we discuss potential mechanisms of action for σ2R/TMEM97 in pain modulation by drawing insights from its known biological activities in other contexts. By synthesizing current knowledge of the role of σ2R/TMEM97 in pain modulation, this review identifies gaps in the current pain literature and encourages future research into this promising biological target.