Drug Combo Blocks Pain Without Impairing Movement
WEDNESDAY, Oct. 3 -- A visit to the dentist could one day involve no pain and no numbness, Harvard researchers report.
In experiments with rats, the scientists combined capsaicin -- the ingredient that makes chili peppers hot -- and a drug called QX-314. This combination blocked pain-sensing neurons without the side effects of numbness or paralysis that typically accompany current pain relievers.
"We found a way to target local anesthetics to block only pain fibers," said lead researcher Dr. Clifford Woolf, the Richard Kitz Chair of Anesthesia Research at Harvard Medical School. "At present, any standard local anesthetic blocks pain fibers and fibers that produce numbness and paralysis. We have managed to block pain fibers without the numbness or paralysis."
QX-314 is a derivative of the lidocaine, a common local anesthetic. But QX-314 alone isn't able to get into cells to block electrical activity, and thus pain. When capsaicin is added, it opens the cell membranes of pain-sensing neurons and lets QX-314 into the cell.
One expert thinks the discovery could one day be used to treat some types of chronic pain.
Ways of suppressing localized pain haven't improved much since the advent of aspirin, explained Edwin W. McCleskey, scientific officer at the Howard Hughes Medical Institute and author of an accompanying journal editorial.
"It's basically aspirin and morphine," he said. "That's why a new strategy is big news."
"This has only been done in rats, so it is unclear that it is going to work on humans," McCleskey noted.
In the study, Woolf's team found that the combination of capsaicin and QX-314 blocked pain-sensing neurons without affecting other nerve cells.
In additional experiments, the researchers injected the drugs into the paws of rats and found that the animals could tolerate more heat than usual. They also tried the drug combination on the nerve that runs down the rat's hind leg. These rats did not show any signs of pain, and five of the six moved and behaved normally. This showed that the drugs could block pain without affecting the nerves that control movement.
Woolf noted that this type of anesthetic could make dental visits easier. "Someone going to the dentist would be able to have a dental procedure without numbness," he said.
The anesthetic also could be used during childbirth. "The woman would feel something, but not pain," Woolf said. "More importantly, she would be able to walk instead of being paralyzed for some time, and there wouldn't be a reduction in blood pressure, which is a major reason why after an epidural people have to be monitored and kept flat," he said.
A problem with the treatment is that the capsaicin can cause burning sensations until the QX-314 takes effect. But giving QX-314 about 10 minutes before the capsaicin minimizes this problem, Woolf noted.
The researchers are looking for ways to prevent the burning sensations. "We need to get a formulation that is as effective in humans as it was in the animals," Woolf said.
They are also looking for ways to prolong the pain relief and at the possibility of developing a pill instead of using injections, Woolf said.
McCleskey thinks this new method of pain control could treat conditions such as sciatica.
"There, you know the nerve that is causing pain, and if you could inject this cocktail into that nerve you could just eliminate pain," he said. "That would be huge."
For more information on pain, visit the U.S. National Library of Medicine.
Posted: October 2007
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