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“Itch gene” found—relief for scratchers at hand?

July 25, 2007
Courtesy Washington University 
School of Medicine
and World Science staff

Are you scratching yourself to distraction? Re­lief may come soon, sci­en­tists claim: they’ve found what they call the first known gene that con­trols the itch sensa­t­ion in the spi­nal cord or brain.

With a ge­ne­tic tweak, re­search­ers pro­duced mice that seem live bliss­fully itch-free lives.
The re­search­ers pro­duced mice with­out the gene, that seem to lead bliss­fully itch-free lives. The work may quickly lead to ef­fec­tive new treat­ments for chron­ic, se­vere itch­ing, they pre­dicted.

The “itch gene” is called GRPR, which stands for gastrin-releasing pep­tide re­cep­tor. The gene codes for the pro­duc­tion of a re­cep­tor—or mo­lec­u­lar gate­way for chem­i­cal sig­nal­s—found in a small num­ber of spi­nal cord nerve cells. These cells trans­mit pain and itch sig­nals from the skin to the brain. 

Lab mice lack­ing the gene scratched much less than nor­mal when giv­en itchy stim­u­li, said the re­search­ers, led by Zhou-Feng Chen at the Wash­ing­ton Un­ivers­ity School of Med­i­cine in St. Lou­is. The find­ings ap­pear in an ad­vance on­line edi­tion of the re­search jour­nal Na­ture this week.

Chron­ic itch­ing, a wide­spread prob­lem, can re­sult from skin dis­or­ders, or from deeper prob­lems such as kid­ney fail­ure or liv­er dis­ease. It can be a se­ri­ous side ef­fect of can­cer ther­a­pies or pow­er­ful painkillers. Chron­ic itch­ing can dis­rupt lives, in­ter­fer­ing with sleep or lead­ing to scars from all the scratch­ing. And ef­fec­tive treat­ments are few.

Itch re­search has been a bit ne­glected be­cause it “has lived in the shad­ow of pain re­search,” Chen said. “No one knew which gene was re­spon­si­ble for itch­ing in the brain or in the spi­nal cord un­til now.” 

Even Chen’s team be­came in­ter­est­ed in GRPR be­cause they were look­ing for pain-related genes. Among those they were ex­am­in­ing, GRPR stood out be­cause it’s found only in these few spi­nal cord cells. They be­gan to study some mice that were mis­sing the gene. 

Re­sults were “a lit­tle dis­ap­point­ing at first,” Chen said, since the “knock­out” mice seemed to feel pain just as as oth­er mice. But then a post-doctoral fel­low, Yan-Gang Sun, in­jected the spi­nal cords of nor­mal mice with a sub­stance that stim­u­lates the gene. The ro­dents started scratch­ing them­selves stre­nously.

“That’s when we thought the gene might be in­volved in the itch sensa­t­ion,” Chen said. Fu­ture treat­ments for itch might in­volve sub­stances that in­ter­fere with the GRPR re­cep­tor mol­e­cule, he added, such as by at­tach­ing them­selves to it and gum­ming up their func­tion. Luck­i­ly, a few GRPR-dis­rupting sub­stances are al­ready known, he added, so all that needs to be done may be to go ahead and start test­ing them. “Now re­search­ers can study the ef­fect of these agents on the itch sensa­t­ion and pos­sibly move that re­search to clin­i­cal ap­plica­t­ions fairly soon.”

* * *

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Itching for a better anti-itch remedy? Your wish may be granted soon, scientists claim: they’ve found what they call the first known gene that controls the itch sensation in the spinal cord or brain. The researchers produced mice that lead blissfully itch-free lives. The work may quickly lead to effective new treatments for chronic, severe itching, they predicted. The “itch gene” is called GRPR, which stands for gastrin-releasing peptide receptor. The gene codes for the production of a receptor—or molecular gateway for chemical signals—found in a small number of spinal cord nerve cells. These cells transmit pain and itch signals from the skin to the brain. Lab mice lacking the gene scratched much less than normal when given itchy stimuli, said the researchers, led by Zhou-Feng Chen at the Washington University School of Medicine in St. Louis. The findings appear in an advance online edition of the research journal Nature this week. Chronic itching, a widespread problem, can result from skin disorders, or from deeper problems such as kidney failure or liver disease. It can be a serious side effect of cancer therapies or powerful painkillers. Chronic itching can disrupt lives, interfering with sleep or leading to scars from all the scratching. And effective treatments are few. Itch research has been a bit neglected because it “has lived in the shadow of pain research,” Chen said. “No one knew which gene was responsible for itching in the brain or in the spinal cord until now.” Even Chen’s team became interested in GRPR because they were looking for pain-related genes. Among those they were examining, GRPR stood out because it’s found only in these few spinal cord cells. They began to study some mice that were missing the gene. Results were “a little disappointing at first,” Chen said, since the “knockout” mice seemed to feel pain just as as other mice. But then a post-doctoral fellow, Yan-Gang Sun, injected the spinal cords of normal mice with a substance that stimulates the gene. The rodents started scratching themselves strenously. “That’s when we thought the gene might be involved in the itch sensation,” Chen said. Future treatments for itch might involve substances that interfere with the GRPR receptor molecule, he added, such as by attaching themselves to it and gumming up their function. Luckily, a few GRPR-disrupting substances are already known, he added, so all that needs to be done may be to go ahead and start testing them. “Now researchers can study the effect of these agents on the itch sensation and possibly move that research to clinical applications fairly soon.”