Pain is a leading cause of disability in the US, affecting more Americans than cancer, diabetes and heart disease combined. But in a new study, researchers say they have discovered an “off switch” for pain, paving the way for new treatments.

The research team, led by Daniela Salvemini, professor of pharmacological and physiological sciences at Saint Louis University, MO, publish their findings in the journal Brain.

According to Prof. Salvemini and her team, there are few successful treatments for chronic pain. “The most successful pharmacological approaches for the treatment of chronic pain rely on engagement of endogenous circuits involving opioid, adrenergic and calcium channel mechanisms,” the researchers note.

These medications, however, can cause severe side effects – such as muscle pain, anxiety, irritability and even drug tolerance and addiction. This can lead to discontinued use, reduced quality of life and inadequate pain relief.

Past studies have shown that a drug called adenosine may be effective for pain relief in humans, but the medication activates an array of circuits, or “pathways,” causing a number of side effects. It has been unclear as to which specific pathway mediates the pain-relieving effects of adenosine, so Prof. Salvemini and her team wanted to find out.


The researchers analyzed more than 300 rodent models of chronic neuropathic pain – pain that results from nerve damage.

They found that activating a receptor in the brain called A3 halted or reversed chronic pain in the rodents, and that this receptor could be activated by a small adenosine molecule and other small-molecule medication created by the National Institutes of Health.

What is more, activating the A3 receptor with a small adenosine molecule did not alter the normal pain threshold in rodents or trigger the reward center of the brain – a process that can lead to addiction with opioid use.

Commenting on their findings, Prof. Salvemini says:

“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.

Our findings suggest that this goal may be achieved by focusing future work on the A3 adenosine receptor (A3AR) pathway, in particular, as its activation provides robust pain reduction across several types of pain.”

The team notes that A3AR agonists are already undergoing clinical trials for treatment of inflammation and cancer, and – as demonstrated in this study – the drugs have caused no serious side effects so far.

“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,” adds Prof. Salvemini.

Medical News Today recently reported that the Food and Drug Administration (FDA) have approved a prescription opioid with abuse-deterrent properties. The drug – Hysingla ER (hydrocodone bitartrate) – forms a thick gel, which makes it difficult to inject, crush, break or dissolve.

Written by Honor Whiteman

<article_copyright>Copyright: Medical News Today

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