Grant: CIHR/RxD - Biology of Pain -Young Investigators Grant

Canadian Pain Society approximates the total cost of chronic pain to the Canadian economy to be $12.5 billion per year and it is estimated that nearly 1 in 3 Canadians suffers from chronic pain, making it the most common form of chronic illness in Canadians under the age of 60. One broad category of chronic pain that is particularly problematic is neuropathic (NP) pain. Treatment of NP pain is particularly challenging, as it is typically refractory to conventional (opioids) and non-traditional (anti- depressants and anti-epileptics) analgesics, or their use is limited by intolerable side effects. Consequently, this factor has led to profound interest in investigating the neural basis of NP pain. Over the past decade, one proposed mechanism underlying NP pain is glial-induced modulation of synaptic activity in pain transmitting neurons. Glia have traditionally be regarded as structural supports for neurons and important for maintaining CNS homeostasis. However, glia have key roles in modulating neuronal communication. Since this discovery, research has linked reactive glia to various chronic pain conditions including NP pain. We have evidence that opioid analgesics increase glial activation and this activity subsequently leads to opioid tolerant states. Preliminary data suggest that ultralow dose opioid antagonists attenuate the development of opioid analgesics but also suppress glial activation as evidenced by changes in cell morphology.