Chronic itch can be a debilitating condition
US scientists have pinpointed a type of nerve cell in mice which appears to generate the itch sensation.
The finding suggests itching is not simply a low-level variation of pain - but a distinct sensation.
A team from Washington University found itch and pain signals seem to be transmitted along different pathways in the spinal cord.
The study, published online by the journal Science, raises hopes of new treatments for itching.
Many scientists have regarded itching as just a less intense version of pain.
They spent decades searching in vain for itch-specific nerve cells to explain how the brain perceives itch differently from pain.
The latest study finally pinpoints these cells - but shows that the low-level pain theory was wrong.
The researchers were able to knock out the itch response in mice without affecting the animals' ability to sense pain and attempt to avoid it.
Lead researcher Dr Zhou-Feng Chen said: "This finding has very important therapeutic implications.
"We have shown that particular neurons are critical for the itching sensation but not for pain, which means those cells may contain several itch-specific receptors or signalling molecules that can be explored or identified as targets for future treatment or management of chronic itching."
The same team identified an "itch gene", called GRPR, in 2007.
This time, they injected the spinal cord of mice with a toxin that killed off cells in which the gene was active.
There are many causes of itch, including more than 50 diseases including shingles, Aids, gallbladder problems and Hodgkin's Disease
The itch produced by many diseases can greatly affect quality of life and cannot always be treated
It is not clear that itch serves any clear purpose in many cases
By doing this they were able to eliminate the scratch response in some animals completely.
However, the same animals continued to respond normally to pain.
This showed that the key cells were active in transmitting the sensation of itching, but not the sensation of pain.
There are two major types of itching. One, caused by bug bites or allergic reactions, is linked to the presence of the chemical histamine.
But most chronic, severe itching is not linked to the chemical - and does not respond to standard anti-histamine treatment.
However, mice whose itch cells had been destroyed did not scratch, regardless of the type of itching agent to which they were exposed.
Dr Glenn Giesler, an expert in itch at the University of Minnesota, said: "I believe this work is very important.
"It could pinpoint targets for future treatments for itch, a common and sometimes debilitating condition produced by more than 50 diseases."
However, Professor Gil Yosipovitch, another expert in the field at Wake Forest University in North Carolina, said the pathway uncovered by the latest study was not the only one that could transmit the itch sensation.
He said other work suggested there were other pathways which transmitted both the sensations of itch and pain.
He also warned that there was a long way to go from work on mice to the development of new drugs for humans.
However, he added: "It could surely help develop new treatments for itch.
"As yet there are no general purpose anti-pruritic (anti-itch) drugs that target the neural system."