Research Associate Professor of Pharmacology Ph.D., Texas A&M University, 1997Bone Cancer
Common cancers, such as breast and prostate, metastasize to bone eliciting osteolytic and osteoblastic reactions associated with incapacitating bone pain and fracture. Advanced cancer pain is described as "moderate to severe" in approximately 40-50% and as "very severe or excruciating" in 25-30% of the patients. Bone cancer pain is continuous and can be exacerbated by episodes of breakthrough pain. Current therapies for bone cancer pain are palliatative, focusing on alleviating tumor burden and targeting pain. Cancer pain management follows the guidelines outlined in the WHO Ladder Approach for Relief of Cancer Pain that suggest adjusting the strength of the prescribed analgesics according to pain intensity. Opioids are recommended for treatment of moderate to severe cancer pain, with morphine most frequently used. However, many cancer patients require opioid dose escalation to maintain adequate pain relief due to the diminished analgesia with repeated opioid administration (i.e., "analgesic tolerance"), the advancement of the disease resulting in greater pain and therefore requiring more opioid, or both. My laboratory focuses on gaining a better understanding of mechanisms underlying bone cancer pain and disease progression develop new mechanism based therapies to treat cancer pain and cancer related side effects.
Opioid-induced Paradoxical Pain
The chronic nature of cancer pain often requires prolonged opioid administration through controlled release tablets, repeated bolus injections, or transdermal patches. Prolonged opioid administration is associated with adverse side effects including enhanced pain sensitivity, referred to as opioid induced hyperalgesia, and tolerance. These effects contribute to dose escalation which can result in patients receiving very high doses of opiates which are associated with abnormal pain, somnolence, confusion, constipation, and an overall diminished quality of life. My current research determines neurobiological changes associated with prolonged opioid administration to develop a better understanding of mechanisms underlying opioid-induced hyperalgesia. A better understanding of mechanisms underlying opioid induced hyperalgesia will lead to the development of novel therapies that can counter these adverse effects of opioids enhancing the pain alleviating effects of opioids administered across prolonged time periods. Moreover, an important aspect of my current research determines how these changes impact treatment of bone cancer pain.
King, T., Pawar, S.C., Majuta, L., Sroka, I.C., Wynn, D., Demetriou, M.C., Nagle, R.B., Porreca, F. and Cress, A. Integrin modulation decreases prostate cancer migration and bone pain. PLoS ONE. In press.
Vardanyan, A,Wang, R,Vanderah, TW,Ossipov, MH,Lai, J,Porreca, F, and King, T. TRPV1 Receptor in Expression of Opioid-Induced Hyperalgesia. The Journal of Pain, In Press, Corrected Proof.
King, T., Vardanyan, A., Majuta, L., Melemedjian, O., Nagle, R., Cress, A.E., Vanderah, T.W., Lai, J. & Porreca, F. Morphine treatment accelerates sarcoma-induced bone pain, bone loss, and spontaneous fracture in a murine model of bone cancer. Pain 132, 154-168 (2007).
King, T., Ossipov, M.H., Vanderah, T.W., Porreca, F. & Lai, J. Is paradoxical pain induced by sustained opioid exposure an underlying mechanism of opioid antinociceptive tolerance? Neurosignals 14, 194-205 (2005).
King, T.E., et al. The role of alpha 6 integrin in prostate cancer migration and bone pain in a novel xenograft model. PLoS ONE 3, e3535 (2008).
Vardanyan, A., et al. TRPV1 Receptor in Expression of Opioid-Induced Hyperalgesia. J Pain (2008) (Epub ahead of print).