Grant: CIHR Fellowship

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. The Zamponi lab discovered a previously unrecognized mechanism that contributes to the development of chronic pain states. 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 electrical impulses depend on ion channels, and among these are T-type calcium channels which regulate electric signals and communication between nerve cells in the spinal cord. When these T-type channels are too active, or when there are too many of them, there is increased pain signalling, and this is exactly what appears to happen in chronic pain conditions. The lab discovered how this occurs at the molecular level, and now know that this is mediated by an enzyme called USP5 which prevents the calcium channels from being normally degraded. USP5 is activated during chronic pain states and increases the number of T-type calcium channels, thereby facilitating the propagation of pain signals. We will now build on our exciting findings and a considerable body of work from our lab to determine how this process takes place at the molecular and cellular level, and how we can use this information to design new avenues for treating chronic pain conditions.