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Wednesday, October 3, 2007

New anesthesia method blocks pain without numbness or paralysis

By Colin Nickerson, Globe Staff

The world's hottest work in anesthesiology is being done at Harvard, where researchers are pouring pepper on pain.

Scientists at Harvard Medical School and Massachusetts General Hospital today described a new "targeted" approach to anesthesia that uses the active ingredient in chili peppers as part of an ingenious recipe for blocking pain neurons. Most critically, the technique doesn't cause the numbness or partial paralysis that is the unwelcome side effect of anesthesia used for surgery performed on conscious patients.

If approved for use in humans, the method could dramatically ease the trial of giving birth -- by sparing women pain while allowing them to physically participate in labor. It could also diminish the trauma of knee surgery, for instance, or the discomfort of getting one's molars drilled. Not only would there be no "ouch," there would be none of the sickening wooziness or loss of motor control that comes from standard forms of "local" anesthesia.

In time, the process might even be employed for major surgery on the heart and other organs, the researchers said. More prosaically, the work might also represent a breakthrough cure for the common itch.

The work on lab rats, described in the scientific journal Nature, breaks from the standard approach to local anesthesia, which usually involves anesthetics delivered by catheter tubes or injections that silence all neurons in a given region of the body, not just those that sense pain. Shutting down just the pain neurons means that patients could still feel a light touch and other non-hurtful sensations.

"This could really change the experience of, for example, knee surgery, tooth extractions, or childbirth," said Dr. Clifford Woolf, senior author of the study and a researcher in anesthesia and pain management at Mass. General. "The possibilities are almost endless."

Woolf collaborated with Bruce Bean, professor of neurobiology at Harvard Medical School, in research that employed surprisingly basic scientific principles as well as some unlikely ingredients -- capsaicin, the stuff that imparts "hot" to chili peppers, as well as an all-but-forgotten variation of a standard anesthesia, long dismissed as clinically useless.

"We plucked a little of this and little of that off the shelves," Bean said. "The project is really a great illustration of how basic biological principles can have very practical applications."

Indeed, scientists with no involvement in the Harvard study were most surprised by its simplicity.

"It's a really clever piece of work, based on one of those 'I wish I'd thought of that' ideas," said Dr. Stephen G. Waxman, head of the department of neurology at Yale University's School of Medicine. "This is an important piece of research."

There's also sweet historic symmetry to the discovery.

Boston, after all, is the city that invented feeling no pain -- at least in surgery.

Modern anesthesia was first successfully employed in surgery in October 1846, one of the greatest moments in medicine. In Boston's Public Garden, the second-largest statue -- after that of George Washington on his horse -- is a soaring pillar, adorned with roaring lions and bas-relief depictions of 19th Century surgeons, that celebrates the "discovery that the inhaling of ether causes insensibility to pain. First proved to the world at the Massachusetts General Hospital."

Not far away, modern Mass. General's original "ether dome" still stands, a national landmark and popular pilgrimage point for anesthesiologists from around the world.

The work undertaken by Woolf, Bean and post-doctoral researcher Alexander Binshtok exploits well-known concepts of how electrical signals in the nervous system depend on ion channels -- proteins that make passageways through the membranes of nerve cells. Pain-sensing neurons possess a unique channel protein, TRPV1, but one that is usually blocked by a molecular "gate."

Medicine for more than 150 years has relied on general and standard anesthetics that penetrate and suppress sensation in all neurons, not just those nerve cells dedicated to sensing pain. That's why an epidural or a simple shot of Novocain leaves a whole region of the body numb or paralyzed, because all nerves cells are affected.

Enter the hot chili pepper, in the form of capsaicin.

Enter, too, a failed derivative of the common anesthetic lidocaine, invented in the 1940s. The derivative, known as QX-314, was deemed useless because it couldn't penetrate cell membranes to block sensation. In non-pharmaceutical terms, that's a bit like having a power shovel that can't cut earth.

In experiments, the Harvard researchers found that the chili pepper ingredient generated heat that opened the gate to pain neurons, but had no similar effect on other nerve cells. Then, when they introduced the lidocaine derivative, it charged through the open channels to block pain in those neurons, but was still unable to enter other nerve cells, such as "motor" neurons that control coordination and mobility.

Thus, in rat experiments, there appeared to be a total shutdown of pain, with no apparent numbness or paralysis.

The rats received injections near nerves leading to their hind feet, and lost the ability to feel pain in their paws. But they continued to scamper about their cages normally and showed sensitivity to touch and other stimulation.

"We introduced a local anesthetic selectively into specific populations of neurons," said Bean. "Now we can block the activity of pain sensing neurons without disrupting other kinds of neurons that control movements or non-painful sensations."

Experimentation will likely move on to to sheep, then humans. One problem that needs to be addressed is whether the capsaicin might cause such a burning sensation when first injected -- before the lidocaine derivitive shuts down the pain -- that it may be too uncomfortable for use as an anesthetic. But the researchers are confident they can find a more practical "warming" chemical to open the gateways to the pain neurons.

"This method could really transform surgical and post-surgical analgesia. Patients could remain alert without suffering pain. But they also wouldn't have to cope with numbness or paralysis," Woolf said.

Noting that itch-sensitive neurons are similar to nerves that sense pain, he added: "We may have even found a good treatment for the common itch."

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