A comprehensive review on pain: Model, target, therapy, and prospect (Review).

Pain serves as both a protective physiological response essential for species survival and a global health issue affecting human well‑being and societal development. The present review systematically summarized and analyzed the research progresses on pain through a multidimensional analytical framework encompassing animal models, molecular targets, therapeutic approaches and future prospects. In animal modeling, neuropathic pain paradigms have evolved from traditional mechanical compression to composite models that combine dynamic displacement and chemical stimulation. Cancer‑induced pain models employ orthotopic tumor transplantation to recapitulate bone metastasis and soft tissue invasion mechanisms and visceral pain models combine inflammatory mediators with mechanical distension to replicate clinical manifestations. The above animal models are the main models of pain, each with its own characteristics and applicable scope. The studies of molecular targets have identified voltage‑gated ion channel, G protein‑coupled receptor signaling cascades, and inflammation‑related enzymes as critical analgesic targets, providing a molecular basis for the design of new analgesic drugs. New targets for treating pain are still being studied. Clinical treatment strategies are showing a trend of multimodal integration, with breakthroughs in opioid optimization and non‑opioid innovation in drug therapy, precise analgesia achieved through neuromodulation techniques in intervention therapy, and strengthened chronic pain management dimensions through physical and psychological interventions. Although there are a number of means for treating pain, the research on drugs that can truly cure pain has still a long way to go. The future research and development of analgesics will focus on in‑depth analysis of pathological mechanisms, adverse reactions of opioid drugs, personalized analgesic strategies, and interdisciplinary transformation.