|July 28, 2000
WASHINGTON (AP) - For years, doctors operated on premature
babies without anesthesia in the belief that even if the
infants felt the pain, they would not remember it. New
research with rats suggests that the body does remember the
pain and is forever changed.
A study using newborn rats at the National Institutes of
Health found that painful trauma that mimics medical
procedures commonly performed on premature infants caused the
rats to become much more sensitive to pain as they grew older.
The reason is that pain causes the developing nervous
system of the very young to grow more nerve cells that carry
the sensation of pain to the brain, NIH researcher M. A. Ruda
"We found that there are more nerve endings that fire and
transmit the (pain) information," said Ruda, the first author
of a study appearing Friday in the journal Science. "These
animals later were more sensitive and had a greater response
Ruda said the study only suggests what may happen in
"This is animal research so one has to be cautious in
extrapolating to humans," she said. "But we use these animals
as models of pain and they have been very valid for predicting
the responses that one sees in humans."
The study is part of a continuing effort by medical science
to understand how and when the nervous system develops and how
the growth of nerve tissue is affected by stimulation, such as
pain. Such research has a direct bearing on efforts to save
and improve the lives of infants born prematurely, before the
normal 40-week gestation.
Survival of babies born up to 15 weeks premature is now not
unusual, but it takes a major medical effort and many painful
procedures, including countless needle sticks, breathing tubes
and even surgery.
Just how much pain such babies feel has been uncertain,
said Dr. Patricia A. McGrath, a pain researcher and professor
of pediatrics at the University of Western Ontario, who was
not a member of the Ruda research team.
Ten years ago, she said, "there was a real belief that the
pain system in premature babies was not developed and these
infants would really not feel as much pain."
More important, McGrath said, doctors had concerns that
premature infants given powerful anesthetics "would not be
able to clear the drug as well as older infants." The choice
sometimes was between skipping anesthesia during lifesaving
surgery or passing on any therapy. Most doctors chose life and
hoped that the pain caused no lasting effect.
But Ruda said that the study in rats suggests there is a
lasting effect, a change in the nervous system caused by the
trauma. If this conclusion is the same in humans, she said, it
could mean that premature infants who endured pain of major
medical therapies may have a sharpened sensitivity to pain all
In the study, Ruda and her colleagues injected an irritant
that causes pain into the left rear paw of day old rats. Lab
rats at that age are in the same development stage as human
babies born at 25 weeks of gestation.
The paws were sore for several days before healing. Later,
when the rats were grown, the researchers tested their
perception of pain by exposing the treated paw to heat. In
effect, the test was to see how fast the animals would
withdraw from a hot surface. Their reaction time was compared
with that of control rats that had not been treated.
Ruda said the treated rats reacted to the heat about twice
as fast as the control rats.
When the heat test was administered on the right, or
untreated paw, of the test rats, they reacted just as did the
control rats. This suggested that the painful trauma early in
life had made the treated paw much more sensitive to pain.
Microscopic examination of nerves in the animals showed
why, Ruda said.
Nerves leading from the treated paw were much more dense
than were the nerves in the untreated paw or in control
animals, she said. The increased density means there were more
nerve circuits to carry pain stimuli to the brain, Ruda said.
Ruda said other studies have shown that premature babies
tend to report more pain in their childhood years and their
parents report that these children's pain response is greater
than their siblings'.
Dr. Jonelle C. Rowe, an NIH doctor who specializes in
treating premature babies, said surgery without anesthesia was
rare. Even now, procedure such as insertion of a breathing
tube, which require painkillers in adults, are done without
anesthesia in premature babies.
"We use anesthesia as well as we can in these babies," Rowe
said. A major research effort is under way to find the best
way to safely relieve medical procedure pain in the very