RESEARCH KNOCKS OUT PAIN

A CU psychologist discovers that opiates irritate certain cells,
making the drugs less effective. The finding offers hope for chronic sufferers.

University of Colorado psychologist Linda Watkins has successfully
used a genetherapy technique to treat laboratory rats suffering
chronic pain. (Special to The Denver Post / Larry Harwood)

Boulder - Morphine works wonders for a broken bone, but barely takes
the edge off the phantom pain of an amputated limb.

Chronic pain is notoriously difficult to treat, and University of
Colorado psychologist Linda Watkins thinks she knows why. Her answer
has the potential to change the way doctors manage patient pain.

"It's the glia," Watkins said, referring to a class of cells that has
suddenly emerged as the hottest target of anti-pain medicine.

"Glia don't like morphine. It irritates them," Watkins said.

Irritated glial cells, Watkins has discovered, mess with the ability
of morphine to calm down everyday pain neurons.

A research team, including Watkins, reports its findings in a paper
scheduled for the December issue of the academic journal Trends in
Neuroscience.

The research could help explain why opiate withdrawal is so painful.

It has already spawned a business connection between Watkins and the
California company Avigen Inc., which is studying two drugs to calm
down overexcited glia.

Drugs currently used to manage chronic pain are woefully inadequate,
Watkins said. For the ongoing agony of a back injury, an amputation
or chemotherapy, pain drugs considered "good" still fail 60 percent
to 80 percent of the time, she said. Chronic-pain victims respond
poorly to opiates, or need very high doses, she said.

"It's a horrible situation. These are not minor issues. These are
people who commit suicide," Watkins said.

The American Pain Foundation estimates that one in four U.S. adults
suffers chronic pain, and for some, it's completely debilitating.

Robert Schwartzman, chair of the neurology department at the Drexel
University College of Medicine in Philadelphia, works with people who
develop a complicated pain syndrome after seemingly minor injuries,
such as whiplash.

"They get narcotics but they remain in terrible pain," Schwartzman
said. "They sit home and lose their jobs and friends."

Schwartzman and others have known for several years that certain
chemicals - called cytokines - are somehow involved in that ongoing
pain, but it took Watkins to explain how.

Glial cells, which become overactive during exaggerated pain
responses, pump out cytokines, she found. Opiate drugs make it worse,
exciting glia and counteracting the effect of the pain drug.

"That's a really major advance," Schwartzman said. "Now we're finally
starting to understand this pain business."

Watkins used a gene-therapy technique to treat overexcited glial
cells in laboratory rats suffering chronic pain, with clear results.
She injected genes that coax spinal cells to make anti-inflammatory
cytokines. The treatment calmed the glial cells, but didn't affect
normal pain neurons.

Rats that previously avoided using a painful paw began running
around, Watkins said. "We turned off neuropathic pain completely."

Watkins said she expects Avigen to begin clinical trials with a
similar technique next year.