Molecule may play role in pain reception

by Peter Kauffner

University lab rats helped researchers find new evidence on the source of pain — literally by the skin of their teeth.
The research, to be published today in the British scientific journal Nature, suggests that a molecule called adenosine triphosphate is used by damaged tissue to signal pain to the nervous system.
“We think that it is probably ATP in most cases (of pain) that gets the nervous system going,” said Robert Elde, dean of the University’s College of Biological Sciences and a professor of cell biology.
Others are not so sure that the discovery is quite that important.
“There are many different types of pain and there are many known mediators of pain, so ATP is most likely just one of the players,” said Lucy Vulchanova, graduate student in the neuroscience program who assists Elde.
The chemical is known to be an energy transmitter and has also been suspected of being a pain signal for the past 15 years.
“ATP is the energy source that every cell depends on,” Elde said. “It’s like an Eveready battery for every cell.”
The researchers applied chemicals to tooth pulp taken from the teeth of rats.
“Tooth pulp is an area where many, if not all, of the nerves are poised to sense pain and maybe nothing other than pain,” Elde said. In other parts of the body, pain-sensing nerve cells are mixed together with other nerve cells that sense heat, stretch, pressure and vibration.
“Rats are an experimental animal of a size that we can deal with them,” Elde said. “Their nervous system is well studied.”
The nerves in the tooth pulp responded to the application of ATP by firing in a particular pattern that indicates the presence of P2X3, a type of protein that acts as a receptor of ATP.
When ATP was applied to a muscle nerve, it fired in a pattern that indicated the presence of a receptor other than ATP.
These results suggest that P2X3 is the receptor that causes ATP to be sensed by the nervous system. If a drug could be developed that chemically blocked P2X3, it would have the potential to be a powerful pain killer.
“We’d like to develop a drug to block only P2X3,” Elde said. “Such a drug would work against pain, but not against the ability to sense muscle stretching or whatever. Several drug companies are excited about this.”
Elde said that the trickiest part of the experiment was the development of methods to analyze the nerves in tooth pulp.
“The tooth pulp is encased within a very hard bony layer of tooth,” Elde said. “It’s very difficult to get in there without damaging the nerve fibers in the process.”
Elde and his fellow researchers are now attempting to work out the exact structure of the pain receptors. The receptors appear to contain five or six sub-units, at least one of which is made of P2X3.
To determine the composition of a receptor, the researchers immunize an animal in such a way that its immune system produces antibodies that seek out particular proteins suspected of being present in a receptor.
“We make antibodies that specifically recognize a certain protein,” said Vulchanova. “We use these antibodies to stain different tissues and then we visualize the antibodies using fluids and molecules.”
Elde’s research was funded by a grant from the National Institutes of Health.