pharmphys

Samson WK: The evolving story of orexin biology: the hits keep coming. f1000 Biology Reports 2009, 1:85.
Specific URL: http://f1000biology.com/f1000reports/articles/10.3410/b1-85/article.html

Orexin Receptor Subtype Activation and Locomotor Behavior in the Rat.
Willis K Samson, Sara L Bagley, Alastair V Ferguson, and Meghan M White
Acta Physiol (Oxf), November 4, 2009; .(online) PMID 19889100

Zahm D.S., Becker M.L., Freiman A.J., Strauch S., DeGarmo B., Geisler S., Meredith G.E., and Marinelli M.: Fos after single and repeated self-administration of cocaine and saline in the rat: emphasis on the basal forebrain and recalibration of expression. Neuropsychopharmacology, advance online publication, September 30, 2009; doi:10.1038/npp.2009.149.

CJ Price, WK Samson, AV Ferguson. Neuropeptide W has cell phenotype-specific effects on the excitability of different subpopulations of paraventricular nucleus neurons. Journal of Neuroendocrinology 21: 850-857, 2009. PMID 19686447

Bryant L, Doyle T, Chen Z, Cuzzocrea S, Masini E, Vinci MC, Esposito E, Mazzon E, Petrusca DN, Petrache I, Salvemini D. Spinal ceramide and neuronal apoptosis in morphine antinociceptive tolerance. Neurosci Lett. 2009 Sep 29;463(1):49-53. Epub 2009 Jul 23.

Kucenas, S., Cox, J.A., Soto, F., LaMora, A. and Voigt, M.M. (2009) Ectodermal P2X receptor function plays a pivotal role in craniofacial development of the zebrafish. Purinergic Signaling 5:395-407.

Thanks to a two year, $974,024 NIH-funded ARRA (American Recovery and Reinvestment Act) grant, Saint Louis University and Southern Illinois University Edwardsville researchers are working to find better ways to manage chronic pain by treating neuroinflammation.

One-third of all Americans suffer from some sort of chronic pain, and the estimated cost of managing it with pain medication is $100 billion each year. Of those patients, 30 percent are resistant to pain killing medications. Chronic neuropathic pain, common with arthritis, cancer, diabetes and nerve injuries, can be debilitating and the ability to manage pain is a major determiner of quality of life. Current treatments often have varying degrees of effectiveness as well as side effects.

Working to address this problem, Daniela Salvemini, Ph.D., associate professor of pharmacological and physiological science at SLU School of Medicine and William Neumann, assistant professor of medicinal chemistry in the SIUE School of Pharmacy, are leading a study to find a new approach to pain management drugs. Over the past decade, Salvemini's pioneering research led to the discovery of a key compound called peroxynitrite that is produced when there is inflammation in the body. It is the overproduction of this molecule that can cause chronic pain.

 "We discovered a substance, peroxynitrite, which turns out to be very important in the development of pain and inflammation. If we target that molecule, we hope we can find new therapies with fewer side effects," said Salvemini. "Currently, pain is often poorly managed. Our hope is to find better ways to eliminate human suffering.

"I'm so pleased that we are partnering with SIUE on this important work that has the potential to ease the pain of millions."

With peroxynitrite identified, researchers now will aim to target and destroy the offending molecule.

"Dr. Salvemini has pioneered some of the landmark preliminary pharmacological research and we're now working together to create a medicine to combat the chronic pain by targeting peroxynitrite," said Neumann.

"When you have inflammation in the body, reactive oxygen and nitrogen species are produced, which can lead to formation of the neurotoxic molecule, peroxynitrite," said Neumann. "Normally, these reactive molecules are kept under tight wraps by the body's own antioxidant defense systems. But, if these systems become compromised, as in a state of chronic pain, it actually can make the problem worse. We'll be looking at creating a synthetic enzyme that will go in and destroy the peroxynitrite."

The study is being funded by the NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Dr Salvemini has been invited to speak at the "Biology and genetics in the pathogenesis of atherosclerosis: basic research and clinical implications" that will be held in Rome, Italy on October 16-17 2009. The title of her seminar will be "Novel antioxidants for therapeutic use in vascular injury and inflammation"