While searching for novel painkillers, a team of KU Leuven researchers came to the surprising conclusion that some candidate drugs actually increase pain.
At the cellular level, pain involves the stimulation of a network of pain nerves spread through the skin, mucosa and bodily organs.
Embedded in the cell wall surrounding these nerves are ion channels. These tiny, microscopic pathways respond to stimuli such as extreme cold or heat, mechanical pressure or harmful chemicals. When ion channels open, an electrical signal is created, transmitted to the brain, and interpreted as pain.
a particular ion channel – TRPM3 – acts as a molecular fire detector: the ion channel detects heat and the hormone pregnenolone sulfate, a precursor to the sex hormones estrogen and testosterone and a trigger for pain and inflammation. In the present study, the researchers were looking for TRPM3 inhibitors that could potentially be used as painkillers.
Surprisingly, their results show that a number of drugs meant as painkillers actually increased pain in mice
“Normally, when the ion channel is closed, no electrical signal is sent to the brain and therefore no pain is detected. But we found that pain can indeed occur despite a closed ion channel. How? A short circuit in the ion channel. When short-circuiting occurs, the electrical signal effected by a stimulus does not follow the normal pathway through the central pore of the ion channel. Instead, it navigates an alternative path through the surrounding material. This ‘electrical leak’ activates the pain nerves, thus increasing the sensation of pain. This may explain the pain-enhancing side effects of some drugs – such as clotrimazole, a common remedy for yeast infections that often causes unpleasant side effects such as irritation and burning sensations.”
“It is striking that short circuits in the ion channel only occur at high hormone levels. This could explain why some patients experience these side effects while others do not,