Itch pathways and TRP channels

BioMed Radio - Washington University School of Medicine in St. Louis

Researchers have found how sensory nerve cells work together to transmit itch signals from the skin to the spinal cord, where neurons then carry those signals to the brain. Their discovery may explain why some people experience various types of itching, including chronic itching, and help scientists find ways to make some types of itching stop. The researchers report that by interfering with the activity of sensory neurons, they may be able to inhibit multiple types of itching.

THERE ARE SPECIFIC NEURONS IN THE SPINAL CORD THAT CARRY ITCH SIGNALS TO THE BRAIN, BUT BEFORE THOSE CELLS CAN BE ACTIVATED, OTHER SENSORY CELLS MUST PROCESS AND TRANSMIT ITCH SIGNALS. NOW, RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS HAVE IDENTIFIED CHANNELS IN NERVE CELLS THAT CARRY DIFFERENT TYPES OF ITCH SIGNALS TO THE SPINAL CORD. AND THE FINDINGS MAY GIVE SCIENTISTS NEW TARGETS TO HELP BLOCK OR RELIEVE ITCHING IN SOME PATIENTS. JIM DRYDEN HAS MORE�

THE RESEARCHERS STUDIED HOW ITCH SIGNALS ARE PROCESSED IN THE DORSAL ROOT GANGLION. THAT�S A CLUSTER OF NERVE CELLS THAT CARRIES SIGNALS FROM THE SKIN TO THE SPINAL CORD. ZHOU-FENG CHEN, DIRECTOR OF WASHINGTON UNIVERSITY�S CENTER FOR THE STUDY OF ITCH, SAYS THERE WERE TWO CALCIUM CHANNELS IN THE CELLS IN THAT STRUCTURE THAT WERE KNOWN TO BE INVOLVED IN TRANSMITTING DIFFERENT TYPES OF ITCH � KNOWN AS HISTAMINE-INDUCED ITCH, WHICH IS THE TYPE OF ITCHING THAT CAN BE TREATED WITH ANTIHISTAMINES LIKE BENADRYL, AND CHLOROQUINE-INDUCED ITCH, WHICH OFTEN EFFECTS PEOPLE WHO TAKE THE DRUG CHLOROQUINE FOR MALARIA. CHEN SAYS CALCIUM CHANNELS IN NERVE CELLS CALLED TRPV1 AND TRPA1 PROCESS THOSE ITCH SIGNALS.

(act) :20 o/c of histamine

TRPV1 is required for histamine, a very important itch mediator.
And TRPA1 is very important for chloroquine-mediated itch. So
these two types of itch are very different because chloroquine-
mediated itch is independent of histamine.

MEANING THAT ANTIHISTAMINES DON�T DO MUCH FOR PATIENTS WITH CHLOROQUINE-INDUCED ITCHING. BUT, STUDYING MICE, CHEN FOUND THAT A THIRD CALCIUM CHANNEL, CALLED TRPV4, ALSO WAS REQUIRED FOR CHLOROQUINE-INDUCED ITCH.

(act) :12 o/c itch sensations

Not only that. We also found TRPV4 also is required for histamine.
So, therefore, here you have one channel mediating two types of
very distinct itch sensations.

HE SAYS IT APPEARS THERE�S SOME CROSS-TALK BETWEEN THESE ITCH-PROCESSING CHANNELS IN THE NERVE CELLS.

(act) :24 o/c is surprising

There are so many TRP channels co-expressed in sensory neurons,
and there�s lots of cross-talk, but then, there are really no
studies of behavior, physiologically relevant studies to show
this kind of two TRP channels in a sensory cell may cross-talk
to relay each specific type of itch. So this is surprising.

AND CHEN SAYS THE SURPRISING DISCOVERY OF CROSS TALK BETWEEN THE THE V4 CHANNEL AND THE OTHER, PREVIOUSLY DISCOVERED ITCH-TRANSMITTING CHANNELS MEANS THAT SCIENTISTS AND DRUG MAKERS MAY HAVE ANOTHER TARGET THAT COULD BE USED TO BLOCK MULTIPLE TYPES OF ITCH SIGNALS.

(act) :13 o/c additional target

V4 is an important target, for both histamine-induced itch and for
chloroquine-induced itch. Our data suggest that it�s probably a very
important channel for the chloroquine itch, so you have an additional
target.

CHEN AND HIS COLLEAGUES REPORT THEIR FINDINGS IN THE JOURNAL SCIENCE SIGNALING. I�M JIM DRYDEN…

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