A specific potassium channel responsible for mediating the analgesic effects of morphine, but not the adverse side effects, is identified in a study in this week’s Nature Communications. These findings may help to develop pain treatments that have minimal side effects.
Morphine is highly effective in treating some forms of acute and chronic pain, however its use is often limited by associated negative side effects. The main side effects include constipation, respiratory depression and addiction. Morphine exerts its effects by acting at morphine receptors and is known to have indirect effects on the activity of potassium channels that control the excitability of neurons that transmit pain. The TREK-1 potassium channel is one such channel implicated in pain perception that Alain Eschalier and colleagues studied for its response to morphine. In mice that were lacking TREK-1 potassium channels, they found that morphine exerted a reduced analgesic effect, but still affected constipation, respiratory depression and dependence to the same extent as in normal mice. This suggests that only the positive analgesic effects are mediated by TREK-1 potassium channels.
Although these studies were conducted in mice, the authors hope that these findings will lead to further translational research using compounds that selectively activate TREK-1 potassium channels, resulting in new pain relief drugs with maximum efficacy and minimal side effects.