Progress in pain mechanisms and management.

Pain is a multifaceted sensory and emotional experience that profoundly affects human health and quality of life. It functions as a double-edged sword: while acute pain serves as a protective warning signal, chronic pain compromises physiological and psychological well-being. Pain is now widely regarded as the "fifth vital sign," and given its rising prevalence and substantial global burden, chronic pain may also be considered a major chronic disease entity. Accordingly, elucidating the neural and molecular underpinnings of pain and developing effective analgesic strategies remain urgent priorities. This review provides a comprehensive overview of the molecular and neural circuit mechanisms that govern pain. At the molecular level, ion channels, diverse receptor systems, and intricate signaling pathways play central roles in the transduction and modulation of nociceptive signals. At the circuit level, pain processing involves ascending pathways, descending modulatory systems, and distributed brain regions that collectively encode the sensory and affective dimensions of pain. Building on these mechanistic insights, we discuss current therapeutic strategies, including pharmacological and nonpharmacological interventions, as well as emerging approaches such as gene therapy, stem cell-based therapies and neuromodulation. Despite notable progress, several challenges remain, including the adverse effects associated with existing analgesics and an incomplete understanding of visceral pain mechanisms. Future research should prioritize the integration of multiomics approaches, advanced neural circuit mapping technologies, and artificial intelligence to refine mechanistic insights and enable the development of more precise and effective pain management strategies.