Activating the Adenosine A3 Receptor Subtype Is Key to Powerful Pain Relief
In research published in the medical journal Brain, Saint Louis University researcher Daniela Salvemini, Ph.D. and colleagues within SLU, the National Institutes of Health (NIH) and other academic institutions have discovered a way to block a pain pathway in animal models of chronic neuropathic pain including pain caused by chemotherapeutic agents and bone cancer pain suggesting a promising new approach to pain relief.
Daniela Salvemini, Ph.D.
The scientific efforts led by Salvemini, who is professor of pharmacological and physiological sciences at SLU, demonstrated that turning on a receptor in the brain and spinal cord counteracts chronic nerve pain in male and female rodents. Activating the A3 receptor – either by its native chemical stimulator, the small molecule adenosine, or by powerful synthetic small molecule drugs invented at the NIH – prevents or reverses pain that develops slowly from nerve damage without causing analgesic tolerance or intrinsic reward (unlike opioids).
An Unmet Medical Need
Pain is an enormous problem. As an unmet medical need, pain causes suffering and comes with a multi-billion dollar societal cost. Current treatments are problematic because they cause intolerable side effects, diminish quality of life and do not sufficiently quell pain.
The most successful pharmacological approaches for the treatment of chronic pain rely on certain “pathways”: circuits involving opioid, adrenergic, and calcium channels.
For the past decade, scientists have tried to take advantage of these known pathways – the series of interactions between molecular-level components that lead to pain. While adenosine had shown potential for pain-killing in humans, researchers had not yet successfully leveraged this particular pain pathway because the targeted receptors engaged many side effects.
A Key to Pain Relief
In this research, Salvemini and colleagues have demonstrated that activation of the A3 adenosine receptor subtype is key in mediating the pain relieving effects of adenosine.
“It has long been appreciated that harnessing the potent pain-killing effects of adenosine could provide a breakthrough step towards an effective treatment for chronic pain,” Salvemini said. “Our findings suggest that this goal may be achieved by focusing future work on the A3AR pathway, in particular, as its activation provides robust pain reduction across several types of pain.”
Researchers are excited to note that A3AR agonists are already in advanced clinical trials as anti-inflammatory and anticancer agents and show good safety profiles.
“These studies suggest that A3AR activation by highly selective small molecular weight A3AR agonists such as MRS5698 activates a pain-reducing pathway supporting the idea that we could develop A3AR agonists as possible new therapeutics to treat chronic pain,” Salvemini said.
The research was funded in part by the National Cancer Institute (NCI), (RO1CA169519) and the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) at the NIH in Bethesda, Maryland.
Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious diseases.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov
Carrie Bebermeyer | EurekAlert!
Spanish scientists create a 3-D bioprinter to print human skin
24.01.2017 | Carlos III University of Madrid
Tracking movement of immune cells identifies key first steps in inflammatory arthritis
23.01.2017 | Massachusetts General Hospital
A Swedish-German team of researchers has cleared up a key process for the artificial production of silk. With the help of the intense X-rays from DESY's...
For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.
According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
24.01.2017 | Physics and Astronomy
24.01.2017 | Life Sciences
24.01.2017 | Health and Medicine