Scientists find molecular key to paradoxical pain: study pinpoints trigger of burning by anesthetics

Science News, July 19, 2008 by Ashley Yeager

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"Relax. Keep counting," the anesthesiologist says to the patient, who is having her hip surgically replaced. "You won't feel a thing."

Though the woman can no longer feel the dull ache in her hip, she can feel a prickly burning in her arm where a general anesthetic drips intravenously into her veins. It is a sensation she doesn't remember the doctor telling her about, she thinks, as she forces herself to mouth a few more numbers.

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For years, patients have reported a burning feeling at the site of a general anesthetic injection, or in the lungs when inhaling gaseous forms of the drugs, which put a patient into an unconscious sleep. But doctors could not pinpoint where the pain response originated.

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Now scientists have confirmed the patient perspective and identified the pain-promoting trigger associated with anesthesia. What's more, some anesthetics can also increase pain after surgery by adding to swelling of the tissue being operated on, a team of scientists from Georgetown University in Washington, D.C., reports in the June 24 Proceedings of the National Academy of Sciences.

The ion channel protein called TRPA1 is present on sensory neurons, found in most body tissues. Anesthetics activate this protein, also called the mustard-oil receptor, causing nerves to fire electrical signals. That message tells the brain that something painful is happening.

"Probably what is most significant for people to know is that this activation of a pain channel actually adds to post-surgery inflammation, so what we didn't know before was that you could exacerbate swelling of surgery-damaged tissue with general anesthetics," says Georgetown neuroscientist Gerard Ahern, who oversaw the new study with lead author and Georgetown postdoctoral researcher Josd Matta. "I don't think anyone has ever considered that before."

Until now, scientists did not understand how anesthetics activate and sensitize pain-response neurons in the peripheral nervous system. So anesthesiologists have not known how to reduce the drugs' painful side effects. The findings may lead to development of new anesthetics or increased use of the few anesthetics that don't add to post-surgery pain and inflammation.

"Now that we know the mechanism that triggers these ill side effects ... we can get closer to finding a single agent, a single general anesthetic to use rather than a bunch of drugs together," says Tim Hales of George Washington University in Washington, D.C., a neuropharmacologist not involved in the research. "The fewer drugs we have to administer, the safer it is for the patient. That single anesthetic is the ultimate, long-term goal."

Studying the inflammatory effects of different anesthetics in humans will also help doctors determine whether the pain of more inflammation is worth the benefit of healthier tissue healing, says Robert Pearce, chair of the anesthesiology department at the University of Wisconsin-Madison.