Activating Adenosine A3 Receptor Alleviates Chronic Pain In Rodents

Chronic pain can occur for many reasons, including chemotherapy or nerve damage from diabetes. The most common drug treatments for chronic pain rarely alleviate pain entirely, and some have unintended consequences such as being addictive. Daniela Salvemini of St. Louis University School of Medicine and colleagues have found that activating adenosine A₃ receptors in the brain and spinal cord can counteract chronic nerve pain in male and female rodents (Brain 2014, DOI: 10.1093/brain/awu330). Researchers have studied adeno­sine receptors as chronic pain targets, but they have focused on the A₁ and A_2A receptors—pathways that can lead to cardiovascular side effects. Salvemini’s team instead activated the A₃ receptor either by treating the animals with an agent to boost in vivo adenosine concentration or by administering MRS5698, a selective A₃ adenosine receptor activator invented by NIH’s Kenneth A. Jacobson and coworkers. Both approaches alleviated chronic pain in rats and mice without producing the drug tolerance seen with morphine. Other adenosine A₃ receptor activators are in human clinical trials for nonpain indications, and reports suggest they have good safety profiles.