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Helen, Queen of Pain --OR, Why Artie is So Sensitive

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  • Ed Wells
    http://www.post-gazette.com/healthscience/20010129smartmice4.asp Mice genetically modified to be smarter may feel more pain Monday, January 29, 2001 By Byron
    Message 1 of 1 , Jan 29, 2001
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      Mice genetically
      modified to be smarter
      may feel more pain

      Monday, January 29,

      By Byron Spice, Science
      Editor, Post-Gazette

      Mice that have been
      genetically modified to boost their memory and learning
      abilities may not only
      be smarter than the average mouse, but painfully so.

      A new study by
      neuroscientists at Washington University School of Medicine
      in St. Louis found that
      the same brain cell modification that made the so-called
      "Doogie" mice smarter
      may also have sensitized them to chronic pain.

      The study findings,
      being published in the February issue of the journal Nature
      Neuroscience, are not
      clearcut. The researchers found evidence that
      persistent pain seemed
      to be enhanced and that the mice even responded to
      what should have been
      non-painful touches. But it's also possible that the mice
      might have been
      displaying a learned response, rather than feeling actual pain.

      But the study is a
      cautionary reminder that genetic manipulations meant to
      enhance a desirable
      trait can have side effects that may prove detrimental,
      said Min Zhuo, a
      neuroscientist and one of the lead scientists of the
      Washington University

      Genetic enhancement,
      such as designer babies, is something that most
      scientists insist is
      still far in the future. A national panel of experts last year
      concluded that
      inheritable genetic modifications are not yet safe and should be
      banned until procedures
      and standards are in place. And no one claims to
      know precisely which
      genetic changes are necessary to safely make a person
      smarter, more charming
      or a more talented athlete, musician or writer.

      Nevertheless, the
      recent news that Oregon scientists have transferred a
      foreign gene into a
      near relative of humans, a rhesus monkey, has renewed
      speculation about
      designer babies. The earlier creation of the smart mouse,
      announced in September
      1999, likewise seemed to suggest that increasing
      intelligence by genetic
      changes might turn out to be relatively simple.

      That was an
      understandable reaction, admits Joe Tsien, the Princeton
      neurobiologist whose team developed the smart mouse. But that
      wasn't the team's
      intention, or conclusion. Rather, they created the mouse
      strain, dubbed Doogie
      after the precocious TV character Doogie Howser, to
      test a 50-year-old
      theory about how memory works.

      Scientists had
      speculated that memories are stored and behaviors are learned
      by strengthening or
      weakening various connections between brain cells in the
      forebrain. Proteins on
      the surface of brain cells, called NMDA receptors,
      were known to play a
      role in changing the strength of these interconnections.

      So Tsien created a
      mouse with extra copies of NR2B, a gene that produces
      one type of NMDA
      receptor. Tests, including some by Zhuo, showed that the
      mice did indeed have
      better memory and more learning ability, as predicted
      by the theory.

      That did not
      necessarily make the mice more intelligent, Tsien emphasized last
      week. "Learning and
      memory is just one component of intelligence," he said.
      But it did suggest that
      memory and learning might be enhanced by drugs that
      targeted the NR2B gene.

      The researchers
      realized, however, that the same changes in brain
      interconnections that
      affected memory also could affect pain perception, or
      even contribute to drug

      In the latest
      experiments, Zhuo and his colleagues in St. Louis found that the
      Doogie mice responded
      to acute pain, such as hot and cold, in the same way
      as regular mice. But
      when their hind paws were injected with substances that
      cause prolonged
      discomfort and inflammation, the researchers noticed that the
      transgenic mice
      displayed more painful reactions or would withdraw their
      paws when touched, even
      thought the amount of inflammation was the same.

      Based on that evidence,
      Tsien isn't sure the transgenic mice necessarily are
      feeling greater chronic
      pain. "I'm not sure if that produces a perception of pain
      or records a memory of
      pain," he said. They may simply have learned better
      than other mice what to
      expect of certain painful experiences.

      If the mice are feeling
      greater chronic pain, however, the experiment may
      serve not only as a
      warning about the side effects of genetic modification, but
      provide a clue to
      treatment of chronic pain. Rather than using opiates that
      numb chronic pain
      sufferers and make them sleepy, it may be possible to
      design drugs that
      target NR2B instead, relieving chronic pain while preserving
      protective reflex
      responses to acute pain.
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