Osteoarthritis is a chronic knee disease characterized by joint cartilage degeneration and secondary hyperostosis. Pain is the earliest and most important symptom of osteoarthritis patients. With the increase of adverse reactions to other types of analgesic drugs, there is an urgent need for the emergence of new analgesic drugs. In this review, we introduced the role of nerve growth factor (NGF)/tropomyosin receptor kinase A (TrKA) signal axis in pain occurrence, advancement of NGF/TrKA research in the pain and pathogenesis in patients with osteoarthritis, and analgesic drugs associated with NGF/TrKA signal axis, including NGF inhibitors, analgesics that inhibit the combination of NGF and TrKA, and TrKA inhibitors, to provide more drug options for treatment of patients with osteoarthritis.