Grant: Project Grant

Thousands of Canadians (1/5) live with chronic pain in their daily lives, pain that can start with an injury, infection or autoimmune disease but persists long after the initial inflammation subsides. This unresolved form of pain is caused by maladaptive processes (sensitization) that take place at the periphery and in the brain. Clinical pain management relies mainly on opioid drugs, however the recent "opioid epidemic", generated by the limited analgesic effect and the addictive properties of narcotics demonstrates that our understanding of the regulatory mechanisms of opioid receptor function in pathological pain is far from complete. Our project will delineate the mechanisms by which sensitization modulates opioid analgesia. We have identified the Transient Receptor Potential channel Vanilloid member 1 (TRPV1) channel, as a central regulator of opioid receptor function during inflammation. TRPV1, also known as capsaicin receptor, is an important sensor of inflammatory mediators and thus contributes to the transmission and modulation of pain signals. Using genetic, pharmacological and molecular approaches, we will set out to define the mechanisms of TRPV1 - opioid receptor interaction and determine the role of TRPV1 in opioid analgesia. Our findings could validate the use of available TRPV1 ligands, such as capsaicin cream, as combination therapy that improves opioids efficacy, mitigate the development of tolerance and thus relieve the suffering of millions of people worldwide.