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."
Les Lang | EurekAlert!
Live probiotics can re-balance the gut microbiome and modify immune system response
20.11.2018 | Symprove
Purdue cancer identity technology makes it easier to find a tumor's 'address'
16.11.2018 | Purdue University
Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.
Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
19.11.2018 | Event News
09.11.2018 | Event News
06.11.2018 | Event News
21.11.2018 | Power and Electrical Engineering
20.11.2018 | Life Sciences
20.11.2018 | Life Sciences