Scientists identify promising off-switch for chronic pain

Scientists have identified the A3 receptor in the brain as a potential off-switch for chronic pain (Image: Shutterstock)

The more successful ways of reducing chronic pain such as that arising from bone cancer and chemotherapy rely on blocking certain brain pathways, but these aren't without their of side effects. Scientists at St Louis University have discovered that the pathway A3AR could be the key to mitigating pain without some of the unwanted baggage, potentially pointing to new methods of therapeutic treatment.

The release of opiates, the harnessing of calcium and the targeting of adrenergic receptors are all existing approaches to pain relief. But the scientists says these can bring on another set of problems, such as impacting quality of life and inadequate suppression of pain.

Another potential agent for pain-killing is a small molecule called adenosine, though this is also known to trigger considerable side effects. But the St Louis researchers, led by Daniela Selvemini, a professor of pharmacological and physiological sciences, have discovered that the properties of a particular receptor in the brain could see adenosine used in viable therapeutic treatments.

“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,” says Salvemini. “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.”

The scientists showed that by switching on the A3 receptor in the brain, they were able to shut out chronic nerve pain in rodents. This receptor can be activated either through the natural stimulant adenosine or through synthetic drugs. They observed that it either prevented or reversed pain caused by nerve damage, without the typical side effects such as increasing a patient's tolerance to medication.

Advanced clinical trials are already underway, investigating the method's efficacy as anti-inflammatory and anticancer agents, with subjects showing good safety profiles.

The research was published in the journal Brain.

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