get a GRIP on this (longish)

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Posted by Miguel ( on March 03, 2000 at 00:20:56:

Interesting article:

November 29, 1999
'Silent' Nerve Pathways May Cause
Chronic Pain

There's much that's not understood about chronic pain and body processes that
produce it. A recent study may provide new approaches to managing this pain by
targeting part of the nervous system that, until now, researchers didn't know had
anything to do with pain.

A multicenter team led by researchers from the Washington University School of
Medicine in St. Louis, Missouri, looked at how certain nerve cells in the spinal cord
transmit pain signals. Using samples of spinal cord from laboratory rats, they
discovered that pain sensations can be transmitted by a group of nerve connectors
(synapses) that are normally inactive.

Pain sensations happen when nerve receptors on the skin, muscle, or internal
organs send an electrical impulse along a nerve fiber to the base of the spinal cord.
There, another nerve cell passes the signal up the spinal cord to the brain, which
translates it into feelings of pain. It's because signals have to cross a junction, or
synapse, that permits interference with them. For example, many painkillers block
the synapse so the message never reaches the brain.

The spinal cord contains a network of synapses that normally don't do anything.
Researchers have known about these "silent synapses" for years, but until recently
lacked the technology to study them.

In this study, published in the November 1999 issue of "Nature Neuroscience," the
researchers report that silent synapses can be activated by strong pain signals and
by messages sent from the brain to the spinal cord. Pain signals from the brain
cause a protein called GRIP to attach itself to a nerve cell receptor called AMPA.
When this happens, the receptor "awakens" the silent synapse and makes the
signal stronger. Once activated, the silent synapses stay activated, sending pain
signals even when there's no stimulus.

The researchers created a protein fragment, or peptide, to block the brain's signal
by binding to the AMPA receptors and displacing GRIP. This kept the silent
synapses silent, but allowed cells to communicate with other cells normally.

The authors think silent synapses may be over-sensitive to nerve signals, amplifying
them even when a stimulus isn't painful. They say this could explain two aspects of
chronic pain: hyperalgesia, where painful stimuli are felt as more painful than they
ought to be, and allodynia, where normally non-painful stimuli, such as a gentle
touch, are felt as painful.

Knowing how this network of silent synapses works means it might be possible to
block it. The researchers suggest that using peptides to keep GRIP from attaching
to receptors is one way, and blocking the brain chemicals that activate the silent
synapses is another.

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