Featured Research

from universities, journals, and other organizations

Cell Protein Suppresses Pain Eight Times More Effectively Than Morphine

Date:
October 9, 2008
Source:
University of North Carolina School of Medicine
Summary:
Researchers have discovered a new therapeutic target for pain control, one that appears to be eight times more effective at suppressing pain than morphine.

Image shows PAP (in red) in pain-sensing neurons.
Credit: Mark Zylka, Ph.D.

More people suffer from pain than from heart disease, diabetes and cancer combined, but many of the drugs used to relieve suffering are not completely effective or have harmful side effects.

Now researchers at the University of North Carolina at Chapel Hill School of Medicine and the University of Helsinki have discovered a new therapeutic target for pain control, one that appears to be eight times more effective at suppressing pain than morphine.

The scientists pinpointed the identity and role of a particular protein that acts in pain-sensing neurons, or nerve cells, to convert the chemical messengers that cause pain into ones that suppress it.

"This protein has the potential to be a groundbreaking treatment for pain and has previously not been studied in pain-sensing neurons," said lead study author Mark J. Zylka, Ph.D., assistant professor of cell and molecular physiology at UNC. The results of the study will be published online in the journal Neuron, on Wednesday (Oct. 8) and in the print edition the following day.

The biological basis of pain is complex. To study the transmission of painful signals throughout the body, many researchers use "marker" proteins that label pain-sensing neurons. One such marker, FRAP (fluoride-resistant acid phosphatase), has been employed for this purpose for nearly 50 years, but the gene that codes for its production was never identified.

That is, until researchers at UNC found that FRAP is identical to PAP (prostatic acid phosphatase), a protein routinely used to diagnose prostate cancer whose levels increase in the blood of patients with metastatic prostate cancer.

Previous research hinted that FRAP and PAP may have a shared identity. To determine whether or not this was the case, Zylka teamed up with Dr. Pirkko Vihko, a professor from the University of Helsinki who had genetically engineered mice that were missing the gene for PAP. When Zylka and his colleagues studied tissues from these mutant mice, they were happy to see that FRAP activity was missing. This revealed that the two proteins were in fact identical.

Further, the mutant mice proved more sensitive than normal mice to inflammatory pain and neuropathic pain, two common forms of chronic pain in humans. These increased sensitivities diminished when researchers injected excess amounts of PAP into the spinal cords of the mutant mice.

"We were really blown away that a simple injection could have such a potent effect on pain," Zylka said. "Not only that, but it appeared to work much better than the commonly used drug morphine."

The new protein suppressed pain as effectively as morphine but for substantially longer. One dose of PAP lasted for up to three days, much longer than the five hours gained with a single dose of morphine.

The next question for the researchers was how PAP suppressed pain. It is already known that when pain-sensing neurons are stimulated, they release chemicals known as nucleotides, specifically adenosine triphosphate (ATP). This in turn sets off the events that invoke a painful sensation. But if ATP degrades to adenosine, that inhibits the neurons that transmit pain signals, thus relieving pain. Through a series of experiments, the UNC researchers showed that PAP removes the phosphate group, generating adenosine. Their study is the first to identify and characterize the role of such a protein in pain-sensing neurons.

Zylka and his colleagues are now searching for additional proteins that degrade nucleotides in these neurons. They are also working to develop small molecules that interact with PAP to enhance or mimic its activity.

"It is entirely possible that PAP itself could be used as a treatment for pain, through an injection just like morphine," Zylka said. "But we would like to modify it to be taken in pill form. By taking this field in a new direction, we are encouraged and hopeful that we will be able to devise new treatments for pain."

The research undertaken at UNC was supported by grants from the Sloan Foundation, the Searle Scholars Program, the Klingenstein Foundation, the Whitehall Foundation, the Rita Allen Foundation and the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health. The research undertaken at the University of Helsinki was supported by grants from the Sigrid Juselius Foundation, the Finnish Cancer Foundation and the Research Council for Medicine of the Academy of Finland.

Study co-authors include graduate student Nathaniel A. Sowa, research analyst Bonnie Taylor-Blake and research technician Margaret A. Twomey from UNC; and postdoctoral researchers Annakaisa Herrala and Vootele Voikar from the University of Helskinki.


Story Source:

The above story is based on materials provided by University of North Carolina School of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

University of North Carolina School of Medicine. "Cell Protein Suppresses Pain Eight Times More Effectively Than Morphine." ScienceDaily. ScienceDaily, 9 October 2008. <www.sciencedaily.com/releases/2008/10/081008150453.htm>.
University of North Carolina School of Medicine. (2008, October 9). Cell Protein Suppresses Pain Eight Times More Effectively Than Morphine. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2008/10/081008150453.htm
University of North Carolina School of Medicine. "Cell Protein Suppresses Pain Eight Times More Effectively Than Morphine." ScienceDaily. www.sciencedaily.com/releases/2008/10/081008150453.htm (accessed August 28, 2014).

Share This




More Health & Medicine News

Thursday, August 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Mini Pacemaker Has No Wires

Mini Pacemaker Has No Wires

Ivanhoe (Aug. 27, 2014) Cardiac experts are testing a new experimental device designed to eliminate major surgery and still keep the heart on track. Video provided by Ivanhoe
Powered by NewsLook.com
After Cancer: Rebuilding Breasts With Fat

After Cancer: Rebuilding Breasts With Fat

Ivanhoe (Aug. 27, 2014) More than 269 million women are diagnosed with breast cancer each year. Many of them will need surgery and radiation, but there’s a new simple way to reconstruct tissue using a patient’s own fat. Video provided by Ivanhoe
Powered by NewsLook.com
Blood Clots in Kids

Blood Clots in Kids

Ivanhoe (Aug. 27, 2014) Every year, up to 200,000 Americans die from a blood clot that travels to their lungs. You’ve heard about clots in adults, but new research shows kids can get them too. Video provided by Ivanhoe
Powered by NewsLook.com
Radio Waves Knock out Knee Pain

Radio Waves Knock out Knee Pain

Ivanhoe (Aug. 27, 2014) Doctors have used radio frequency ablation or RFA to reduce neck and back pain for years. But now, that same technique is providing longer-term relief for patients with severe knee pain. Video provided by Ivanhoe
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins