Researchers at the University of Illinois at Chicago will use a $2 million federal grant to investigate why patients with sickle cell disease experience chronic pain -- and to develop drugs to treat it.
The neurobiology of pain in sickle cell disease is poorly understood, said Z. Jim Wang, associate professor of pharmacology and pharmaceutics and lead researcher on the four-year study. Research has been conducted using several animal models, but the findings were limited, he said.
In preliminary studies conducted at UIC, Wang and his team observed that CaMKII, an enzyme called a protein kinase that plays an important role in the generation and maintenance of opioid addiction, is a critical component leading to persistent pain. Several pain tests -- some that are employed in ongoing human studies of sickle cell disease using quantitative sensory testing -- will be used on mouse models, Wang said.
Affecting more than 70,000 Americans, sickle cell disease causes red blood cells to become hard and pointed instead of soft and round. Sickle cell disease can damage lung tissue and cause excruciating pain and stroke. The blockage of blood flow caused by sickled cells also causes damage to most organs, including the spleen, kidneys and liver. About 2.5 million Americans have the sickle cell trait.
UIC researchers will examine the expression and activity of CaMKII in mice carrying human sickle mutations and test the hypothesis that spinal CaMKII is a "molecular mechanism that promotes and maintains the manifestation of chronic pain in sickle cell disease," Wang said.
Following the initial studies, Wang and his research team will conduct pharmacological studies using an FDA-approved oral antipsychotic prescription medication -- trifluoperazine -- that is found to be a CaMKII inhibitor that reduces inflammatory and neuropathic pain. The phase I work will be performed in humans with sickle cell disease, he said.
Wang's coworkers include Diana Wilkie, professor of biobehavioral health science; Robert Molokie, instructor in medicine; and Joseph Desimone, director of the UIC Sickle Cell Center. The study is funded by the National Heart, Lung and Blood Institute, one of the National Institutes of Health.
For more information about UIC, visit www.uic.edu
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