2013 pump priming award recipient
Dr Ilona Obara, Durham University
Although opioids, like morphine, remain the most powerful analgesics available for pain relief, their prolonged treatment is limited in efficacy by side effects, including tolerance or opioid-induced hyperalgesia. Additionally, in neuropathic pain that develops after nerve injury, opioid effectiveness is reduced as high doses are required to relieve this type of pain, and tolerance appears rapidly. Understanding of underlying cellular mechanisms may lead to the improvement of opioid efficacy, particularly when prolonged treatment is required.
Recently, the mammalian target of rapamycin (mTOR) kinase has been identified as a novel target for pain relief. In my studies I will employ in vivo models of acute and neuropathic pain and will examine effects of single and/or chronic administrations of inhibitors of mTOR signaling pathway on morphine analgesic effectiveness and on the development of morphine tolerance. I will also examine morphine-induced alterations in mTOR activity within nociceptive pathways using immunohistochemical and immunoblotting techniques.
By establishing the role for mTOR pathway in opioid efficacy, my research will provide novel insights into the molecular adaptations in cellular signaling evoked by repeated morphine administrations leading to the development of side effects in chronic pain patients.
Our understanding of the importance of mTOR signaling in the regulation of opioid efficacy and pain may be therefore of therapeutic clinical benefit.