Researchers use A3 adenosine receptors to activate ‘off signals’ for chronic pain.
In a new study from Saint Louis University, researchers discovered that drugs targeting the A3 adenosine receptor can turn off pain signals in the spinal cord to provide relief from chronic pain. Pain is the most common reason that people seek medical attention, but the available treatments, most commonly non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, are not always successful at relieving pain in patients with chronic pain state the team. For this reason the researchers decided to investigate a new target for treating chronic pain; the A3 adenosine receptor or A3AR.
In previous studies the lab has demonstrated that two drugs which target the A3AR, IB-MECA and MRS5698, were effective in treating several models of chronic pain, including painful chemotherapy-induced neuropathy, metastatic cancer pain, and nerve injury. More recently, the group sought to uncover the mechanism of A3AR pain relief. Chronic pain can result from the loss of regulatory mechanisms in the nervous system pathway that transmits pain, explain the team. Adenosine acts as a regulatory signaling molecule in other areas of the nervous system, so the team hypothesized that A3AR might also play a role in regulating pain signals during pain processing.
Indeed, the team found that A3AR drugs not only relieved pain, but did so by activating an inhibitory transmitter system known as the gamma amino-butyric acid (GABA) system. In areas of the spinal cord and brain dedicated to pain processing, A3AR activation promoted GABA signaling by preventing the breakdown and removal of GABA from neuronal synapses. The team explain that in chronic pain, GABA signaling is often lost or diminished. However, their A3AR drugs were able to restore GABA signaling in areas that process pain and turn off the signals that maintain the pain state.
With the team’s A3AR drugs demonstrating good safety profiles in clinical trials as anti-inflammatory and anti-cancer agents they are enthusiastic about the potential of these new drugs to treat chronic pain in patients.
The lab will continue to investigate the intricate mechanisms underlying A3AR pain relief with the hope of providing better palliative care to individuals suffering from unnecessary chronic pain.