'Off switch' for pain discovered in the brain

Scientists 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.
The study led by Saint Louis University researcher Daniela Salvemini 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 - prevents or reverses pain that develops slowly from nerve damage without causing analgesic tolerance or intrinsic reward.

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.

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," said Salvemini.
The research was published in the journal Brain.