|Treatment Blocks Pain Without Disrupting Other
A combination of two drugs can selectively block pain-sensing
neurons in rats without impairing movement or other sensations
such as touch, according to a new study by National Institutes
of Health (NIH)-supported investigators. The finding suggests an
improved way to treat pain from childbirth and surgical procedures.
It may also lead to new treatments to help the millions of Americans
who suffer from chronic pain.
The study used a combination of capsaicin — the substance
that makes chili peppers hot — and a drug called QX-314.
This combination exploits a characteristic unique to pain-sensing
neurons, also called nociceptors, in order to block their activity
without impairing signals from other cells. In contrast, most pain
relievers used for surgical procedures block activity in all types
of neurons. This can cause numbness, paralysis and other nervous
"The Holy Grail in pain science is to eliminate pathologic
pain without impairing thinking, alertness, coordination, or other
vital functions of the nervous system. This finding shows that
a specific combination of two molecules can block only pain-related
neurons. It holds the promise of major future breakthroughs for
the millions of persons who suffer with disabling pain," says
Story C. Landis, Ph.D., director of the National Institute of Neurological
Disorders and Stroke (NINDS) at the NIH, which funds the investigators'
research along with the National Institute of Dental and Craniofacial
Research (NIDCR) and the National Institute of General Medical
Sciences (NIGMS). The study appears in the October 4, 2007, issue
Lidocaine, the most commonly used local anesthetic, relieves pain
by blocking electric currents in all nerve cells. Although it is
a lidocaine derivative, QX-314 alone cannot get through cell membranes
to block their electrical activity.
That's where capsaicin comes in. It opens large pores called TRPV1
channels — found only within the cell membrane of pain-sensing
neurons. With these channels propped open by capsaicin, QX-314
can pass through and selectively block the cells' activity.
The research team, led by Clifford J. Woolf, M.D., Ph.D., of Massachusetts
General Hospital and Harvard Medical School and Bruce Bean, Ph.D.,
at Harvard Medical School, tested the combination of capsaicin
and QX-314 in neurons isolated in Petri dishes and found that it
blocked pain-sensing neurons without affecting other nerve cells.
They then injected the drugs into the paws of rats and found that
the treated animals could tolerate much more heat than usual. They
also injected the two drugs near the sciatic nerve that runs down
the hind leg. The treated rats did not show any signs of pain,
and five of the six animals continued to move and behave normally.
This showed that the drugs could block pain without impairing motor
neurons that control movement.
The drug combination took half an hour to fully block pain in
the rats. However, once it began, the pain relief lasted for several
"Current nerve blocks cause paralysis and total numbness," Dr.
Woolf says. "This new strategy could profoundly change pain
treatment in the perioperative setting."
The treatment tested in this study is unique in that it uses a
type of ion channel (TRPV1 channels) as an avenue to deliver medication.
Ion channels are pores in the cell membrane that control the flow
of electrically charged ions in and out of cells. "I'm not
aware of any other strategy that uses a channel within cells to
deliver a drug to a select set of cells," Dr. Woolf says.
The strategy builds on research done since the 1970's, largely
supported by NIH, that shows how electrical signaling in the nervous
system results from expression of dozens of different types of
ion channels. Some of these ion channels are found only in specific
types of neurons.
"This project is a nice illustration of how research trying
to understand very basic biological principles can have practical
applications," says Dr. Bean.
This type of treatment has great potential to improve pain treatment
during childbirth, dental procedures, and surgery, the researchers
say. "Surgical pain is the obvious first application for
this type of treatment," Dr. Woolf says. However, similar
therapies might eventually be useful for treating chronic pain,
he adds. Chronic pain continues for weeks, months, or even years
and can cause severe problems, and is often resistant to standard
While the researchers focused on finding a treatment for pain,
this strategy might also be useful for treating itch from eczema,
poison ivy rashes, and other conditions, Dr. Woolf says. Like pain
sensations, itch signals come from nociceptors.
One problem with the combination treatment is that the capsaicin
can cause unpleasant burning sensations until the QX-314 takes
effect, Dr. Woolf says. Administering the QX-314 ten minutes before
the capsaicin minimized this problem in rats. The investigators
are now looking for ways to open the TRPV1 channels without the
burning sensations, perhaps by finding an alternative to capsaicin.
They also hope to find ways of prolonging the pain relief. Eventually,
they might be able to develop pills that will stop pain signals
without requiring injections, Dr. Woolf adds.
Reporters: for more information, call 301-496-5924 or go to www.ninds.nih.gov/PressRequest/.
The NINDS is the nation's primary funder of research on the brain
and nervous system. More information about pain and other neurological
disorders can be found on the NINDS web site, http://www.ninds.nih.gov/.
The NIDCR (http://www.nidcr.nih.gov/)
is the nation's leading funder of research on oral, dental, and
craniofacial health. The NIGMS (http://www.nigms.nih.gov)
supports basic biomedical research that is the foundation for advances
in disease diagnosis, treatment, and prevention. The NINDS, NIDCR,
and NIGMS are components of the National Institutes of Health (NIH).
The NIH Pain Consortium, co-chaired by the NIDCR, the National
Institute of Nursing Research, and the NINDS, strives to enhance
pain research and promote collaboration among researchers across
the many NIH Institutes and Centers that have programs and activities
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.