Grant: Operating Grant

Chronic pain affects as many as 1 in 5 people worldwide. Over the next two decades, as the population ages and modern medicine allows people to survive serious illness, the number of people affected by chronic pain is expected to rise to 1 in 3. Chronic pain can be debilitating, isolating, dehumanizing, and all too frequently, can turn deadly. Understanding the molecular basis of pain is key to the discovery of novel analgesics. Pain transducers are membrane proteins specifically sensitive to the danger signals heat, cold, chemical irritants or ATP. ATP receptors belonging to the P2X ion channel family have been shown to be involved in chronic pain in rodents and primates and they are candidate therapeutic targets for pain treatment without the negative side effects of morphine and pregabalin. P2X3 is expressed exclusively in the pain-sensing neurons located in spinal and trigeminal ganglia. P2X4 is upregulated in spinal microglia following nerve injury and P2X4 activation has been shown to contribute to neuropathy-associated pain hypersensitivity. We propose in this research program to investigate the function and integration of P2X3 and P2X4 receptors in sensory pathways, by understanding how other receptors talk to P2X receptors and by developing novel selective tools to probe P2X function. Our work will generate novel data to assess the potential of P2X receptors as valid targets for the pharmacological treatment of inflammatory and neuropathic pain.