The substance is composed of a normally inactive derivative of the local anesthetic lidocaine, called QX314, and capsaicin, the pain-producing substance in chili peppers.
Capsaicin works by opening channels present only in pain fibers to allow the QX314 only into these cells, where it blocks their function, Woolf explained in the keynote lecture "Using Pain to Block Pain" at the international conference "Development and function of somatosensation and pain" of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany. "This is the first example of using the body's own cellular channels as a drug delivery system, targeting treatment only at pain fibers," he pointed out.
Local anaesthetics are pain killers which are used during operations whereby patients remain alert during the procedure and thus, do not require general anaesthesia. "These common analgesics, including lidocaine, affect, however all neurons in the treated area," Woolf said. As a result, not only are pain receptors blocked but also touch receptors, producing numbness. Neurons, controlling muscles, are silenced as well, producing a temporary paralysis.
In order to specifically block pain receptors and leave touch sensors and motor function unharmed, the scientists used a normally inactive positively charged form of the local anaesthetic lidocaine called QX314. This particular type of lidocaine is special in that it is not able to pass through the cell membrane of neurons because it is charged. Since local anesthetics only operate inside neurons, an injection of QX314 alone is ineffective, unlike lidocaine which passes easily through the membrane of all cells and therefore blocks all neurons.
As QX314 only enters pain neurons and, thereby, acts exclusively as a pain killer, the researchers combined it with capsaicin. Capsaicin binds a membrane receptor which is only present in the membrane of neurons responsible for pain perception. Thus, the chili pepper substance opens channels, enabling QX314 to get into the cell and then block the pain receptors. Using rats, the scientists could show that, when applied to the animals' hind paws, the combination of QX314 and capsaicin exclusively blocks pain receptors. While completely blocking the response to painful stimuli, the animals could, nevertheless, move normally and were responsive to touch.
There is, however, one disadvantage of this current strategy, said Woolf. Capsaicin activates the sensors for pain and heat. "Thus, people's mouths seem to burn when eating very spicy food," he said. "To use the pain killing combination in patients, another way of opening the channel must be found to allow the QX314 into the cell without capsaicin causing its typical painful heat sensation until the QX314 gets into the cell and then kills the pain," commented Woolf. However, he and his colleagues are working on solving this problem and have recently found promising new non-painful ways of targeting QX314 into pain fibers, which they hope will be available soon for example, for dental patients or for mothers-to-be during labor."
Barbara Bachtler | Max-Delbrück-Centrum
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