POSSIBLE NEW APPROACH TO RELIEF FROM CHRONIC PAIN: Drugs Targeting A3 Adenosine Receptor Restore GABA Signaling and Turn Off Pain Signals in Spine; Lead Molecules for Potential Clinical Trials Have Been Identified

In a study published in the April 15, 2015 issue of the Journal of Neuroscience, Saint Louis University (SLU) scientists, led by Professor of Pharmacological and Physiological Sciences Daniela Salvemini, Ph.D., discovered that drugs targeting the A3 adenosine receptor can "turn off" pain signals in the spinal cord to provide relief from chronic pain. The article is titled “Engagement of the GABA to KCC2 Signaling Pathway Contributes to the Analgesic Effects of A3AR Agonists in Neuropathic Pain.” Pain is the most common reason that people seek medical attention, but the available treatments--most commonly non-steroidal anti-inflammatory drugs (NSAIDs) and opioids--are not always successful at relieving pain in patients with chronic pain. For this reason, Dr. Salvemini and colleagues teamed up with researchers from the NIH, the University of Arizona, and two institutes in Quebec, Canada, to investigate a new target for treating chronic pain: the A3 adenosine receptor (A3AR). In earlier studies, Dr. Salvemini's laboratory demonstrated that two drugs that target the A3AR--IB-MECA and MRS5698--were effective in treating several models of chronic pain, including painful chemotherapy-induced neuropathy, metastatic cancer pain, and nerve injury. More recently, the group sought to uncover the mechanism of A3AR pain relief. "Chronic pain can result from the loss of regulatory mechanisms in the nervous system pathway that transmits pain," Dr. Salvemini said. "Adenosine acts as a regulatory signaling molecule in other areas of the nervous system, so we hypothesized that A3AR might also play a role in regulating pain signals during pain processing." Indeed, Dr.
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