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A Soothing Herpes Infection

The virus that causes herpes may someday bring relief, rather than misery. In the current Proceedings of the National Academy of Sciences, biologists show that the herpes virus can shuttle human antipain genes into nerve cells in mice, increasing their tolerance for pain. If the technique works in people, it could be used to relieve chronic pain.

Pharmacologist Steven Wilson at the University of South Carolina, Columbia, and molecular geneticist Joseph Glorioso of the University of Pittsburgh sought to exploit the herpes virus's tendency to take residence in sensory neurons. First, the duo deleted chunks of several of the virus's genes to prevent it from causing disease. They also attached a human gene to it that produces pro-enkephalin, a natural pain-blocking peptide, as well as a second gene that produces a blue dye, to trace the virus's path under a microscope. They then infected mice with the engineered virus.

To determine how the treatment affected the mice, David Yeomans of the University of Illinois, Chicago, watched how they reacted to a standard pain test. Mice pull their paw away from a heat lamp in about 12 to 15 seconds, but they feel pain and yank it back much faster after being sensitized by capsaicin, the active ingredient in hot peppers. Capsaicin stimulates the nerve cells that also cause chronic burning pain in humans. The sensitizing effect "was completely abolished by the virus," Wilson says. The infected mice still withdrew their paws--proving that they could feel normal pain sensations--but the hypersensitivity of chronic pain was gone.

"This is the first evidence that neuropeptide genes delivered in this way can actually have an effect on pain," says Gudarz Davar, an anesthesiologist at Brigham and Women's Hospital in Boston, Massachusetts. Davar is "cautiously optimistic" that gene therapy will eventually be used to control pain in people. Before that happens, he says, researchers must show it works in animal models that more closely mimic human diseases. They also need to make sure that the herpes virus couriers can't revert from friends to foes by "recombining" with active herpes virus lurking in the body.