Targeting microglial Panx1 to treat the adverse effects of repeated opioid use
Canadian Institutes of Health Research
- Grant type: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships (CGS-D)
- Years: 2017/18 to 2018/19
- Total Funding: $105,000
- ANALGESIC TOLERANCE
- chronic pain
- DRUGS- PHARMACEUTICAL SCIENCE/CHEMISTRY & NON MEDICAL USE OF DRUGS
- NERVOUS SYSTEM
- OPIOID-INDUCED HYPERALGESIA
- PHYSICAL DEPENDENCE
- SPINAL CORD
University of Calgary
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No partner organizations found.
Chronic pain is pervasive, insidious, and afflicts 1 in 5 Canadians. Treating chronic pain is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for managing pain. While opioids are potent analgesics for relieving moderate to severe pain, their prolonged use can lead to severe side effects, such as physical dependence (characterized by a withdrawal syndrome upon cessation of opioid use), tolerance (the drug no longer produces the same level of pain relief), and opioid-induced hyperalgesia (a paradoxical increase in pain that develops with repeated opioid use). The risk of these adverse effects has led to concerns by physicians and patients to use opioids for pain management, triggering an emerging issue of under-treatment in chronic pain patients. The goal of my research is to understand how the side effects of opioid use occur, and to find new ways to interfere with these processes. Microglia are key immune cells in the central nervous system that are increasingly linked to the adverse effects of repeated opioid use. As key targets of opioid action, microglia are 'activated' in the spinal cord in response to opioid treatment, yet the underlying mechanisms of how microglia contribute to the negative effects of opioid use remain elusive. This study examines the role of microglial pannexin-1 (Panx1) in opioid withdrawal, tolerance and hyperalgesia. Panx1 channels expressed on the surface of microglia are known to release molecules that modulate neuronal activity. By studying the inner workings of microglia, this research will identify key molecules and processes involved in regulating the negative effects of repeated opioid use, and will improve our current understanding and therapeutic strategies for treating pain. Opioids are the pharmacological cornerstone of pain therapy, and the goal of the proposed research is to decrease the risk of severe side effects that are associated with long-term opioid use.