Treatment and Prevention of Neuropathic Pain with P2Y14 Antagonists

This technology includes the use of selective antagonist for the P2Y14 receptor for the treatment and prevention of neuropathic pain. Neuropathic pain conditions arising from injuries to the nervous system due to trauma, disease or neurotoxins are exceedingly difficult to treat. Clinicians and patients are often left to manage neuropathic pain with opioids, but these approaches are limited by the eventual loss in opioid efficacy with developing tolerance, the occurrence of severe adverse side effects and the strong potential for their abuse. With over 15-20 million people in the US affected by neuropathic pain, a high priority has been placed upon developing novel non-narcotic analgesics. We have discovered that P2Y14 antagonists given systemically reverse neuropathic pain in a well characterized mouse model of neuropathic pain caused by constriction of the sciatic nerve. P2Y14 antagonists may be useful in the pathogenesis of other disorders of the central nervous system such as cognitive deficits (following chemotherapy or traumatic brain injuries) and Alzheimer’s. Neuroinflammatory processes driven by glial activation are key components of neuropathic pain and these other disorders of the central nervous system.