General anesthetics are welcomed for their ability to banish pain during surgery, but some of these drugs increase postsurgical pain and inflammation. Pharmacologist Gerard P. Ahern of Georgetown University and colleagues believe they have found a possible explanation (Proc. Natl. Acad. Sci. USA 2008, 105, 8784). Using cell cultures and mouse studies, the researchers discovered that certain anesthetics activate the TRPA1 receptor on nerve cells. This ion channel protein, which also responds to irritants found in hot peppers and mustard, plays a key role in the biochemical pathways for pain and inflammation. The researchers showed that intravenous anesthetics such as propofol and inhaled anesthetics such as isoflurane activate and sensitize nerve cells. This activation can lead to nerve-mediated inflammation. Although some general anesthetics don't activate the TRPA1 receptor, they might not be as effective as the irritating anesthetics, Ahern says. "This tells us that there is room for improvement in these drugs," he adds. "We hope these findings are ultimately helpful in providing more comfort to patients."