Patients in pain may soon be better treated with fewer side effects
using lower morphine doses combined with newer painkillers, according
to a study reported by researchers from the University of California,
San Francisco (UCSF), in the March 26th issue of Nature.
The research team led by Allan Basbaum, PhD, chairman of anatomy at
UCSF, discovered that mild pain and more intense pain are
biologically distinct and governed by different signaling molecules.
In order to effectively manage intense pain, clinicians should take
these distinctions into account.
"Pain is not a single phenomenon that can always be attacked
with one type of analgesic drug," said Dr. Basbaum.
Two Types of Neurotransmitters
Yu Qing Cao, a graduate student working in Dr. Basbaums
laboratory, conducted key experiments demonstrating that the
neurotransmitters that signal mild pain are different from those that
signal more intense pain. For several years, researchers have known
that the neurotransmitter glutamate is important in signaling pain.
Mr. Cao, along with researchers in the laboratory of Charles Epstein,
MD, professor of pediatrics, developed a "knockout" strain
of mice lacking a gene for substance P and neurokinin A, two members
of a class of neurotransmitters called the tachykinins. By measuring
how long it took the mice to move away from applied mechanical
pressure, or for how many seconds they licked skin after it had been
dotted with pepper extract, Mr. Cao determined that the knockout mice
were as sensitive to mild pain as normal mice but were much less
sensitive to moderate or more intense pain.
The research team concluded that substance P, neurokinin A, or both
are needed to transmit moderate or more intense pain signals.
Although both the mutant and normal mice required the same amount of
morphine to relieve mild pain, the mutant mice, which lacked the
tachykinins, needed less morphine to relieve more intense pain.
"Drug candidates need to be evaluated in the context of a
particular pain syndrome," Dr. Basbaum said. "Pain relief
often may depend on the particular medical condition and on the
quality and intensity of the pain. The undertreatment of pain is a
severe challenge to the quality of life of millions of seriously
ailing people worldwide," added Dr. Basbaum.
"Morphine, the strongest painkiller legally prescribed in the
United States, appears to act across the pain spectrum by inhibiting
the pain signals transmitted by glutamate." However, Dr. Basbaum
feels that morphine is not used as much as it should be because of
misplaced worries about its addiction potential in pain patients.
Research Could Lead to New Analgesics to Be Combined With Morphine
"Physicians need to better understand how to effectively
administer painkillers, including morphine," he added. "But
the new knowledge emerging from rodent studies about how neurokinin
A, substance P, and other neurotransmitters act on different
receptors could lead to drugs that provide good pain relief when used
in combination with lower, less problematic doses of morphine,"
continued Dr. Basbaum. "This could significantly reduce the
negative side effects associated with higher doses of morphine."