Papers of the Week

Chronic neuropathic pain is a major health issue and an economic burden that affects large numbers of people. Patients suffering from chronic pain have a significantly lowered quality of life, and to date there are no effective treatments for neuropathic pain. The P2Y receptor (P2Y R) is a purinergic G-protein coupled receptor that binds nucleotide-sugars. P2RY14 is widely expressed in the body and is found in the immune system and nervous tissues. Few studies provide evidence that P2Y R is involved in pain conditions. In rat traumatic nerve injury-induced pain and post-surgical pain models, P2RY14 transcript levels were found to increase on the same side of the spinal cord as the nerve injury. In addition, P2Y R expression was elevated in an inflammatory pain model after a complete Freund's adjuvant injection in the rat trigeminal ganglia. Taken together, we hypothesize that the P2Y R plays a role in the development and maintenance of neuropathic pain. To test this, we used peripheral nerve injury model of neuropathic pain and tested several novel P2R R antagonists, which had varying potencies and bioavailabilities. Adult male ICR mice went through unilateral chronic constriction of the sciatic nerve, and on day 7 post injury they received a P2Y R antagonist intraperitoneally and the mechanical sensitivity in the hind paws was assessed. The antagonists rapidly (≤30 min) attenuated, some even reversed, mechanical sensitivity in the mice, with maximal effects observed typically within 1 h post-injection, in a dose-dependent manner. Overall, our findings provide evidence that the P2Y R is a potential therapeutic target for treating chronic pain, and its antagonists can be candidate drugs for pain treatment.