Blocking Pain-Sensing Neurons Without Disrupting Other Functions

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Blocking Pain-Sensing Neurons Without Disrupting Other Functions

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

system disturbances.

" 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). NINDS and NIDCR are co-chairs of the NIH

Pain Consortium. The study appears in the October 4, 2007, issue of

Nature.*

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

hours.

" 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 medical treatments.

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.

http://www.medicalnewstoday.com/articles/84604.php