King laboratory publishes research article on cancer-induced bone pain

Tamara King, Ph.D., associate professor for the College of Osteopathic Medicine published an original research paper in the peer reviewed journal of the Society for Neurosciences, The Journal of Neuroscience. The paper, entitled “Mediation of movement-induced breakthrough cancer pain by IB4 binding nociceptors in rat”. Patients with primary and metastatic cancer associated bone pain report persistent ongoing pain that is treated with opioids. In addition, many patients develop breakthrough pain, a transient period of severe pain, often triggered by movement, that occurs even when the background ongoing pain is controlled with opioids such as morphine. Notably, treatment of breakthrough pain is currently addition of opioids leading to very large doses of opioids along with severe side effects. A better understanding of these aspects of cancer bone pain is necessary for development of improved treatments of cancer pain. This paper presented a novel preclinical measure of movement-induced breakthrough pain that is observed in the presence of morphine controlling ongoing pain. This allows for examination of mechanisms that underlie cancer-induced breakthrough pain to guide development of improved therapies designed to improve these patient’s quality of life and diminish adverse side effects associated with the current treatments. Along these lines, this research examined the hypotheses that ongoing pain and breakthrough pain are dependent on different subpopulations of sensory fibers from the tumor-bearing limb. The research demonstrated that movement induces a pain state that is observed in the setting of morphine that blocks ongoing pain, mirroring the clinical observations of breakthrough pain. Mechanistic analyses of sensory neurons innervating the tumor bearing hindlimb demonstrated that blockade of sensory input prevents BTP. More specific analysis of sensory input demonstrated that ablation of a certain subset of pain sensory fibers that bind isolectin B4 (IB4)-binding fibers, prevented movement-induced breakthrough pain. In contrast, blocking input from a different set of pain sensory fibers failed to prevent movement induced breakthrough pain. This provides important new information that can be used to explore novel biological targets that may show improved pain relief for episodes of breakthrough pain in cancer patients with skeletal metastases.

 A significant portion of this research was performed by UNE students working in Dr. King’s laboratory. The lead author, Joshua Havelin (UNE Class of 2011) is currently a graduate student in the Graduate School of Biomedical Sciences and Engineering Program and works in Dr. King’s laboratory at UNE. Ian Imbert (2012) obtained a master of public health degree (MPH) while working on this project in Dr. King’s laboratory and now works for Dr. Dora Mills. Ian Pelletier (2015) worked in Dr. King’s laboratory as an undergraduate at UNE as a double major in the departments of chemistry and biology within the college of arts and sciences (CAS). Ian Pelletier is currently a second year student in the college of osteopathic medicine (COM). Jonathon Gentry a senior undergraduate in the department of medical biology within CAS and will be graduating in May of 2017.

Citation: Joshua Havelin, Ian Imbert, Devki Sukhtankar, Bethany Remeniuk, Ian Pelletier, Jonathan Gentry, Alec Okun, Timothy Tiutan, Frank Porreca, Tamara King. “Mediation of movement-induced breakthrough cancer pain by IB4 binding nociceptors in rats”. Journal of Neuroscience. 24 April 2017, 1212-16; DOI: 10.1523/JNEUROSCI.1212-16.2017

Read the full paper.