Pain And Itch Responses Regulated Separately

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Pain And Itch Responses Regulated Separately

http://medicalnewscenter.com/out/out.cgi?

http://www.sciencedaily.com/releases/2008/11/081117153156.htm

Historically, scientists have regarded itching as a less intense

version of the body's response to pain, but researchers at Washington

University School of Medicine in St. Louis have determined that pain

and itch actually are regulated by different molecular mechanisms.

At Neuroscience 2008, the annual meeting of the Society for

Neuroscience, the researchers report they have separated itch and

pain sensations in mice, a finding that could have important

implications for treating both pain and chronic itching. The two

problems often occur together because when patients are treated with

strong drugs for pain, itching is a common side effect.

Last year, the research team, led by Zhou-Feng Chen, Ph.D., an

investigator at Washington University's Pain Center, was the first to

identify an itch gene. The scientists published those findings in the

journal Nature. Now, further experiments have demonstrated that pain

signals are not affected when mice are bred without the itch gene or

the gene's actions are blocked.

The itch gene, called GRPR (gastrin-releasing peptide receptor),

makes a receptor found in a very small population of nerve cells in

the spinal cord. That region of the spinal cord transmits pain and

itch signals, as well as temperature sensation, from the skin to the

brain. When exposed to itchy stimuli, mice without the gene scratched

less than their normal littermates.

" There are two major types of itching, " says Chen, an associate

professor of anesthesiology, psychiatry and developmental

biology. " There is histamine-dependent itching caused by bug bites or

allergic reactions, the kind of itching that can be treated with

antihistamine drugs, such as Benadryl®. But the majority of chronic,

severe itching is resistant to antihistamine treatment. "

Many patients with chronic pain receive spinal injections of opioid

drugs, such as morphine, to control their pain. One of the well-known

side effects of that treatment is itchy skin.

" Most scientists believed that the itching could not be separated

from the drug's pain-killing effects, " Chen says. " This type of

itching cannot be relieved by anti-histamine treatment. We

hypothesized that GRPR may be responsible for the itching but not

involved in the pain response. "

So Chen's team went back to the mice bred with and without GRPR and

compared both scratching behaviors and pain-killing effects following

spinal injections of morphine. All of the mice got relief from a

mildly painful stimulus, but those without the GRPR gene did not

scratch.

Next they studied normal mice treated with a small peptide that

interferes with GRPR function. When injected with the GRPR blocker,

mice still got morphine's pain-killing benefits, but they did not

itch.

" If we inject a GRPR inhibitor and morphine into the mouse spinal

cord, the drug still has its normal analgesic effect, but the mice

don't scratch, " Chen says. " This is very interesting because it

demonstrates that analgesia and itching can be separated. There may

be itch-specific genetic pathways in the spinal cord that are not

related to pain sensation. "

This result contrasts with a previous finding from Chen's team. In

prior studies when GRPR mutant mice were compared to normal, control

mice, they demonstrated significantly decreased scratching behavior

in response to itchy stimuli, but they still scratched a little. In

this study, however, morphine-induced scratching behavior was

completely eliminated in GRPR mutant mice, suggesting GRPR is

essential in transmitting itching induced by opioids.

Chen says this genetic pathway for itch sensation seems to be

conserved in all mammals. Like mice, humans also have GRPR genes, so

he believes it may be possible to treat chronic itching in humans

with a similar strategy. Those people, he says, would continue to get

pain relief from drugs such as morphine, but they would not feel as

itchy after receiving the drug.

" Our findings could have important therapeutic implications, " Chen

says. " More research needs to be done, but it may be possible to

relieve itching in patients by blocking GRPR function without

affecting the pain pathway. "

Chen ZF, Molecular mechanisms of itch in the spinal cord. Abstract

for Neuroscience 2008. Presented on Nov. 17, 2008.

Related paper: Sun YG, Chen ZF. A gastrin-releasing peptide receptor

mediates the itch sensation in the spinal cord. Nature (448), pp. 700-

703. Aug. 9,2007 (published online July 25,2007).

doi:10.1038/nature06029.

Funding from the National Institutes of Health supported this

research.