In clinical trials so far, it has provided powerful pain relief without sedation or risk of addiction.

Researchers at Japan's Kyoto University Scientists have developed an oral medication that targets the α2B adrenoceptor, a little-studied brain receptor that scientists have found actually plays a major role in mechanical pain. This makes it the first-ever α2B-selective painkiller.

This receptor belongs in the adrenergic receptor family – α2A, α2B, α2C – but no approved drug has targeted a2B to inhibit the receptor with high precision. Existing drugs like dexmedetomidine target broad a2 receptors and in this example's case cause sedation and are not oral. This in itself makes this small-molecule drug candidate, also known as compound c545, a potentially new class of pain-relief drug.

"If successfully commercialized, ADRIANA would offer a new pain management option that does not rely on opioids, contributing significantly to the reduction of opioid use in clinical settings," said corresponding author Masatoshi Hagiwara, a specially-appointed professor at Kyoto University.

The researchers found how a2B becomes more active after nerve injury, and in mice was able to perform the genetic knockout required to inhibit a2B, significantly shutting down neuropathic pain in the animals. However, it's not just applicable for this kind of pain. Preclinical work has shown it has promise for treating inflammatory and post-operative pain too.

ADRIANA (aka adrenergic inducer of analgesia) is the first known compound to selectively block the α2B adrenoceptor. It was able to reverse pain in models of nerve injury, inflammation and post-surgical conditions. And it did this without causing sedation, motor impairment or cardiovascular issues – which has been one of the limitations of A2 receptor drugs to date. It provided powerful pain relief in mice with spinal nerve ligation, paw inflammation and surgical incisions.

Clinical trials at Kyoto University Hospital found that the drug was both safe and tolerable, and effective for patients with postoperative pain following lung cancer surgery. Now, a broader Phase II trial is planned.

"We aim to evaluate the analgesic effects of ADRIANA across various types of pain and ultimately make this treatment accessible to a broader population of patients suffering from chronic pain," said Hagiwara.

This is Japan's first non-opioid analgesic, and could play a pivotal role in relieving pain as effectively as opioids, without the negative outcomes, making it a strong candidate for both post-operative care and chronic pain relief.