Grant: Project Grant

Chronic pain can be a debilitating condition for which there are currently few treatment options, leading to a major burden on our Health care system and a ~$60 Billion loss annually to the Canadian economy due to lost productivity. Pain signals travel along specific nerve cells from the site of an injury to the spinal cord where they communicate with another set of nerve cells that connect to the brain where pain is perceived as an unpleasant sensation. These nerve impulses depend on ion channels, and among these are a group of proteins called N-type calcium channels. In spinal cord synapses, N-type channels control the transmission of pain signals from peripheral nerve fibers to those projecting to the brain. It is known that pharmacological inhibition of N-type channels reduces pain. N-type channels are also inhibited by morphine-induced activation of opioid receptors and by activation of nociceptin receptors. We have discovered that there is a complex interplay between opioid and nociceptin receptor signalling, and have obtained evidence that these interactions are important for analgesic opioid tolerance which is a major problem during the clinical use of morphine. We will now strive to understand the crosstalk between opioid receptors, nociceptin receptors and N-type calcium channels, determine how these receptors regulate channel activity in spinal cord synapses, and to test how these processes contribute to analgesia and opioid analgesic tolerance. This is important because this knowledge will facilitate the development of new therapeutic approaches for the treatment of pain without the adverse affects that are associated with current opioid based therapies.