Researchers have discovered a way to block chronic pain in rodents, including pain caused by chemotherapeutic agents and bone cancer, suggesting a promising new approach to pain relief.
The research, published in the medical journal Brain, 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 synthetic small molecule drugs invented at the National Institutes of Health — prevents or reverses pain that develops slowly from nerve damage, according to researchers at the National Institute of Health and Saint Louis University.
They add that this method of pain relief occurs without causing analgesic tolerance or intrinsic reward, unlike opioids.
Currently, 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, which are 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.
The new study, led by Daniela Salvemini, Ph.D., a professor of pharmacological and physiological sciences at Saint Louis University, 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.”
She added 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 current study was funded, in part, by the National Cancer Institute and the National Institute of Diabetes & Digestive & Kidney Diseases at the National Institute of Health in Bethesda, Maryland.
Source: Saint Louis University