Protein essential for hearing also vital for pain perception

[Guest guest]

Protein essential for hearing also vital for pain perception

26 May 2005 Medical News Today

The same protein that " translates " sound into nerve signals to the

brain and enables individuals to hear is also required for pain

perception, researchers from Northwestern University Feinberg School

of Medicine have found.

Because the protein, TRPA1, is found in the majority - about 75

percent -- of the body's pain-perceiving neurons, but not in major

organs, drugs that could block TRPA1 would be novel pain killers with

few or no side effects, although targeting the inner ear may have to

be avoided, said -Añoveros, who led the research.

-Añoveros, assistant professor of anesthesiology, neurology and

physiology at Feinberg and the Northwestern University Institute for

Neuroscience and a fellow of the Hugh Knowles Center for Hearing

Research, described the dual role of the protein, TRPA1, in the cover

article of the April 20 issue of the Journal of Neuroscience. The

other authors, all members of his research group at Northwestern

University, were Keiichi Nagata, Anne Duggan and Gagan Kumar.

-Añoveros and his colleagues showed conclusive evidence that

TRPA1, in addition to being expressed in nociceptors, or pain

neurons, is present in the stereocilia of hair cells, the sensory

part of the cells of the inner ear used for hearing as well as

detecting gravity and maintaining balance.

-Añoveros and Duggan, currently a research assistant professor

in anesthesiology at Feinberg and a researcher at the Northwestern

University Institute for Neuroscience, initiated the study of TRPA1

in the late 90s, while searching for the channel that mediates

hearing.

After they discovered that TRPA1 is expressed in the organ of Corti,

the hearing organ of the inner ear, they were joined by colleagues at

Harvard Medical School and Northwestern, and thus founded the

groundbreaking group of scientists who in 2004 proposed that TRPA1

was a candidate for mechanosensory channel of hair cells.

In the current study, the Northwestern researchers also demonstrated

that TRPA1 channels display a unique combination of properties

displayed by the hair cell transducer and by no other known channel.

These similarities strongly suggest that TRPA1 is the pore that opens

in response to sound, initiating the electrical signal cascade that

ultimately reaches the brain as we perceive sounds.

But the researchers have also found properties of the TRPA1 channel

that account for its suspected parallel role in pain sensation, such

as why in some cases pain from an injury will not go away as long as

the injury remains.

Essentially, TRPA1 opens in response to painful stimulation, and ions

enter the cell, making it less negatively charged, or depolarized. At

this point most ion channels close, a phenomenon known as

inactivation, because their signaling task has been achieved.

But TRPA1 senses the depolarization and responds to it by staying

open; it will close only when the harmful stimulus goes away.

However, if the depolarization is small, the TRPA1 channels close.

This means that TRPA1 could allow sensory neurons to ignore sustained

innocuous stimuli (such as gentle pressure) but to respond to noxious

stimuli (such as a pinch that causes tissue damage) and remain active

as long as the noxious stimuli persist.

It also means that TRPA1 is sensitized by the opening of other

nociceptor channels in the same sensory nerves; for example, those

that respond to painful heat. This property of TRPA1 may thus account

for painful phenomena in damaged tissues such as lack of

desensitization or even some forms of enhanced sensitization, such as

hyperalgesia (extreme sensitivity to pain) or allodynia (pain

resulting from non-noxious stimuli to normal skin).

" Now we can look for TRPA1 channel blockers, which potentially will

constitute novel analgesics that block pain at its initiation, "

-Añoveros said.

" Such TRPA1 channel blockers should probably be used topically -

preferably avoiding contact with the inner ear - but could also be

applied systemically. In that case the patient might have to put up

with temporary deafness, a side effect that is probably better than

extreme pain. What is critical at this point is to identify drugs or

treatments that very specifically inhibit TRPA1, " he said.

TRPA1 is known to be activated by pain-producing chemicals such as

the pungent components of edibles such as wasabi, horseradish,

mustard, cinnamon and Listerine®, which explains why they sting the

mouth.

The full article is available online at: http://www.jneurosci.org [25

(16):4052-4061].

[Guest guest]

Gretchen,

Could you try to explain this to me in " me " language. It seems very

interesting, but I don't really understand what they're trying to say.

By the way, I went to a wedding 2 days ago, had to buy shoes, ugh!!, got some

slingbacks, and son-of-a-gun....they still fell off!! somehow, someway!! I

walked around barefoot, which hurt so much, but couldn't keep the darn things

on. I even tried on a shoe with a somewhat heel. I almost broke my foot in

Payless!!...Smile, the wedding was beautiful (300 very nice people).

Thanks,