Researchers Discover an 'Off Switch' For Pain in the Brain

Scientists working together from several international universities have discovered that it is possible to block a pathway in the brain of animals suffering from neuropathic pain, which could have a huge impact on improving pain relief in humans.

Pain, an unpleasant sensory and emotional experience triggered by nerve endings reacting to actual or potential tissue damage or disease, is a huge problem in healthcare and the number one reason why people seek medical help.

It is such a big problem that there are many medical journals dedicated solely to pain research.

In the UK alone, back pain alone costs the Chancellor of the Exchequer around £5bn ($7.9bn) in disability benefits a year, according to the British Pain Society, and women suffering from pain-related problems on average lose 55 days from work per annum.

Adenosine as a pain killer

So far, the most successful ways to treat chronic pain from a pharmacological point of view are to create drugs that that interact or interfere with various channels in the brain to decrease pain, including adrenergic, opioid and calcium receptors.

However, there is another way – a chemical stimulator called adenosine that binds to brain receptors to trigger a biological response.

Adenosine has shown potential for killing pain in humans, but so far, no one has managed to harness this pain pathway successfully without causing a myriad of side effects.

Researchers from Saint Louis University Medical School (SLU), University College London, Second University of Naples, University of Arizona and US government agency National Institutes of Health studied chronic nerve pain in male and female rodents.

Their study, entitled "Endogenous adenosine A3 receptor activation selectively alleviates persistent pain states" is published in the journal Brain.

The A3 brain receptor

Led by Dr Daniela Salvemini of SLU, the researchers discovered that by activating the A3 adenosine receptor in the rodents' brains and spinal cords, the receptor was able to prevent or reverse pain from nerve damage (the cause of chronic pain).

The A3 receptor also prevents analgesic tolerance, i.e. when the body gets used to a pain relief medication and gradually the medication becomes less effective, or intrinsic reward, where the individual becomes dependent on a narcotic pain reliever like morphine and self-administers the drug.

"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."

Interestingly, A3AR chemical stimulators are already being used in other advanced clinical trials to prevent inflammation and cancer, and are known to be safe for human use, so this could speed up the time it takes to get approval for the A3 receptor to be used for pain relief.

"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," said Salvemini.