Trang, TuanXu, Yang2017-06-092017-06-0920172017http://hdl.handle.net/11023/3877Opioids, such as morphine, are potent analgesic drugs that are commonly used to treat moderate to severe acute pain. There is also increasing reliance on opioids for managing chronic pain, a pervasive condition that afflicts approximately one in five Canadians. However, prolonged opioid usage can lead to the development of opioid analgesic tolerance, which is characterized by diminished pain-relieving effects. The A3 adenosine receptor (A3AR) is a novel target that produces antinociceptive and anti-inflammatory effects in animal models of chronic neuropathic pain, a condition that shares similar mechanisms with opioid tolerance. We determined that spinal A3AR acutely potentiates morphine antinociception without preventing the development of tolerance. Chronic morphine increased microglia reactivity, MAP kinase activity within the lumbar spinal cord, and cell-surface A3AR protein density on microglia, while spinal A3AR activation abrogated these changes. Overall, these findings have significant implications for improving opioid efficacy in chronic pain management.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.Neurosciencemaster thesis10.11575/PRISM/28315