The discovery of the gastrin-releasing peptide receptor (GRPR) gene in the central nervous system may lead to new therapies to directly target itchiness and provide relief for chronic and severe itching.
The GRPR gene codes for a receptor found in a very small population of spinal cord nerve cells where pain and itch signals are transmitted from the skin to the brain.
Led by Dr. Zhou-Feng Chen, the researchers gave itchy stimuli to mice. They found that rodents who lacked GRPR scratched much less than their normal cage-mates.
Chronic itching is a widespread problem, for which effective treatment options are limited. It can be caused by skin disorders like eczema or from a deeper problem like kidney failure or liver disease. It can be a serious side effect of cancer therapies or powerful painkillers like morphine.
Historically, scientists regarded itch as just a less intense version of the pain sensation, which is why research on itching has been somewhat neglected. Even Dr. Chen's team became interested in the GRPR gene because they had been looking for genes in the pain pathway.
Among potential pain-sensing genes that the researchers identified, GRPR got their special attention because it is present in only a few nerve cells in the spinal cord, which is know to relay pain and itch signals to the brain.
"The research was a little disappointing at first. The knockout mice seemed to have the same reactions to painful stimuli as normal mice," Nature magazine quoted Dr. Chen as saying.
However, when the researchers injected the spinal cords of normal mice with a substance that stimulates GRPR, the rodents began scratching themselves as if they had a bad itch.
"That's when we thought the gene might be involved in the itch sensation. So we began to systematically investigate this possibility," says Dr. Chen.
The researchers studied scratching behaviour in two sets of mice-normal mice and GRPR knockout mice. While normal mice scratched vigorously when exposed to a variety of itch-producing substances, the knockout mice scratched much less.
"The fact that the knockout mice still scratched a little suggests there are additional itch receptors. We know of some proteins that are similar to GRPR, so now we're trying to determine if there is functional redundancy in the itching pathway," Dr. Chen says.
According to researchers, the normal reactions of GRPR knockout mice to painful stimuli were the indications that pain and itch are mediated by separate sets of genes in the spinal cord. Dr. Chen says that this also suggests that drugs can be used to suppress the itch sensation without affecting the pain sensation.
"Scientists have been studying this receptor for more than a decade," Dr. Chen says.
"One interesting thing they've found is that GRPR is implicated in tumour growth. As a result of research like this, a lot of substances have been made that block the activity of GRPR. So now researchers can study the effect of these agents on the itch sensation and possibly move that research to clinical applications fairly soon," adds the researcher.