Grant: Operating Grant

Chronic pain is pervasive, insidious, and afflicts 1 in 5 adult Canadians. Treating pain in these individuals is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for controlling pain. However, a major problem with opioid use is the loss of pain relieving effects (opioid tolerance) such that higher and more frequent doses are necessary to achieve the same level of pain relief. The struggle to maintain adequate pain control decreases the quality of life for chronic pain sufferers and complicates many conditions including cancer, stroke, diabetes, traumatic injury and a host of other diseases. The need for escalating amounts of opioids puts patients at risk for unwanted side effects such as constipation, respiratory distress, and drug dependence. Despite the potential side effects, opioids remain the pharmacological cornerstone of modern pain therapy. Our research focuses on improving the effectiveness of opioids in relieving pain as well as decreasing the side effects associated with opioid therapy. This proposal examines the inner workings of microglia, which are important immune cells in the brain and spinal cord. We will focus on a molecule that is critical for microglia pain signaling in the spinal cord - the P2X7 receptor - and its unique ability to alter communication between cells leading to loss of opioid pain control. By dissembling the cellular machinery that inhibits the ability of opioids to alleviate pain, we can begin to target core components of this machinery to enhance current opioid therapy or help create new options for chronic pain sufferers.