Published online 4 October 2007 | Nature | doi:10.1038/news.2007.140

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Active chemical from peppers allows painkilling without affecting other sensations.

An anaesthetic method that kills pain without producing numbness or preventing movement has been developed.

Pain relief: good for moms-to-be Photodisc

Current local anaesthetics work by indiscriminately blocking all the channels in a nerve cell, so they can block movement and sensation as well as pain.

However, the new technique involves using a combination of two compounds to home in on pain-sensing nerves in a specific area, leaving other functions unaffected. It could prove useful for situations where patients require anaesthetic, but also need to be able to move or control muscles, such as in childbirth and in some dental procedures.

Bruce Bean of Harvard Medical School in Boston, Massachusetts, and his colleagues targeted the pain by taking advantage of an ion channel called TRPV1, which is only present in pain-sensing nerve cells. This channel opens when it senses capsaicin, the active ingredient in chilli peppers.

“It’s a match made in heaven” Michael Caterina

Johns Hopkins University School of Medicine

Working on cultures of neurons, the researchers used capsaicin to open the ion channel, allowing their painkiller of choice — a local anaesthetic called QX-314 — to enter the cell. QX-314 is similar to the commonly-used local anaesthetic lidocaine, but, unlike lidocaine, it has no effect unless it is acting from within a cell. The team found that capsaicin did indeed allow the anaesthetic to only enter pain-sensing neurons, where it could then dampen the action of these cells.

The combination of compounds also worked in live animals. When the team injected rats with QX-314 and capsaicin, the animals didn’t react to a normally-painful stimulus applied to their foot once the painkiller had taken effect. But the rats could move around as normal. The team’s results are reported online in Nature1.

Better together

Capsaicin is already in use as a painkiller for conditions where pain fibres are overactive, says Michael Caterina of Johns Hopkins University School of Medicine in Baltimore, Maryland, who also studies the TRPV1 channel. Applying it overstimulates the nerve endings and de-sensitises them, persuading them to stop overreacting. But, as its link to chilli peppers suggests, it produces an uncomfortable burning sensation and can’t be given in high doses.

Caterina say he thinks the new study is a neat trick, because it may be able to get around this problem. As the capsaicin and anaesthetic are applied at the same time, the capsaicin grants the anaesthetic admission to the cell, where activity is dampened down so that pain (including the burning sensation) is relieved.

“It’s a match made in heaven,” he says. “They’ve taken a number of reagents in common use in pain, and put them together in a very creative way.”

Better for baby

A number of clinical procedures could benefit from a local anaesthetic that doesn’t paralyse or numb the patient. The most obvious is childbirth, where retaining muscle control is important. The commonly-used epidural, which involves injecting anaesthetic into the spine to block the nerves leading to the womb and lower parts of the body, also blocks all movement and feeling, making it harder for the mother-to-be to ‘push’ the baby out.

Another use could be in dentistry, where blocking some nerves can lead to unhelpful drooling. The method could also be used to treat some chronic pain conditions, where constant pain is caused by abnormally active pain fibres.

Developing the technique for clinical use shouldn’t be too difficult because the two substances are already approved for clinical use. “Our prediction is that it should be as safe as lidocaine,” says co-author Clifford Woolf, an anaesthesiologist at Massachusetts General Hospital in Boston. “We think this could lead to a new therapeutic advance quite rapidly.”

Bean believes that a few refinements could make the technique even more effective. “In these initial experiments we used off-the-shelf molecules that we knew about — there may be other agents that would give longer-lasting anaesthesia,” he says.