The importance of P2Rs has increased in various fields in recent years, but this time I will focus on research on pain. Chronic pain is a debilitating condition that often occurs following peripheral tissue inflammation and nerve injury. Especially neuropathic pain is a significant clinical problem because there are few clinically effective drugs. I will review the findings for the role of ATP signaling through P2X3Rs and P2X2/3Rs in primary afferent neurons and through P2X4Rs, P2X7Rs, and P2Y12R in spinal microglia in chronic pain. Many discoveries have strongly accelerated the search for new drugs that target P2Rs, and several compounds have been developed so far in the world. Gefapixant is the only P2X3R antagonist that has finished clinical trials as a refractory chronic cough, and it is under clinical trial for endometriosis-related pain. NP-1815-PX and NC-2600 are recently identified as novel P2X4R antagonists in Japan. NC-2600 has been finished the Phase I study without serious side effects. I think we'll soon get new drugs against pain.