Re: Glutamate transport in ALS (more on glutamate)

[Guest guest]

Found this article. There are other good ones at www.pain.com.

How receptors govern inflammatory pain

Researchers have shown in animal studies how receptors on nerve cells

can become altered to produce chronic pain triggered by inflammation.

They say that their findings could aid in developing new drugs to

treat such chronic pain, which is distinct from the relatively short-

lived pain from injury, which fades as the injury heals.

In their experiments, Bettina Hartmann and her colleagues studied

receptors called AMPA receptors, which are triggered by the

neurotransmitter glutamate. Such receptors are protein switches that

nestle in the membranes of nerve cells and, when triggered, induce

either short-term or long-term changes in the nerve cells. A short-

term change might be the triggering of a single nerve impulse; but

AMPA receptors have been implicated in long-lasting changes such as

adjusting the strength of nerve cell connections, or synapses, in

learning and memory. AMPA receptors regulate nerve cell response by

opening to enhance calcium flow into the cell, heightening the cells'

sensitivity to producing nerve impulses when triggered.

According to Hartmann and her colleagues, studies of spinal cord

tissue showed that AMPA receptors are found in spinal cord regions

known to be responsible for pain sensing, or nociception. However,

they said, there had been no studies that explored what role the

receptors played in whole animals.

To study that role, the researchers genetically altered mice to lack

one or another type of key component, or subunit, of the AMPA

receptor protein. Knocking out one type of subunit, called GluR-A,

would enhance AMPA permeability to calcium; and knocking out the

other, called GluR-B, would reduce its permeability. Normally, the

relative fraction of AMPA receptors with GluR-A or GluR-B on the

surfaces of nerve cells would determine the cell's permeability to

calcium.

Importantly, the researchers found that both of the types of

deficient mice showed normal response to discomforting stimuli, such

as heat. Thus, their pain responses were otherwise normal.

However, when the researchers used chemicals to induced an artificial

inflammation in the paws of the deficient mice, they found

significant differences in responses between the two mutant mouse

strains. The strain with increased permeability of their AMPA

channels was significantly more sensitive to heat or mechanical

pressure on their inflamed paws than were either the strain of mice

with " closed " AMPA channels or the normal mice.

In similar tests, the researchers also found that the altered mice

with more permeable AMPA channels showed evidence of greater

persisting pain from inflammation, compared with the altered mice

with less permeable channels. According to Hartmann and her

colleagues, this difference " supports that acute, short-term

plasticity at central nociceptive synapses is dependent on AMPA

receptors and their composition. "

The researchers also cited evidence from other laboratories that AMPA

receptors might be involved in pain-related changes in the brain that

are " involved in the perception, memory, and emotional modulation of

pain. "

The researchers concluded that " the present study demonstrates that

AMPA receptors are important determinants of pathological nociceptive

sensitivity and suggests their potential relevance in the therapeutic

approaches toward the prevention and treatment of chronic

inflammatory pain.

Bettina Hartmann, Seifollah Ahmadi, A. Heppenstall, R.

Lewin, Claus Schott, Thilo Borchardt, H. Seeburg, Hanns Ulrich

Zeilhofer, Rolf Sprengel, and Rohini Kuner: " The AMPA Receptor

Subunits GluR-A and GluR-B Reciprocally Modulate Spinal Synaptic

Plasticity and Inflammatory Pain "

Publishing in Neuron, Volume 44, Number 4, November 18, 2004, pages

637–650. http://www.neuron.org.

> Hey, thanks a ton for that reference. Theanine and taurine keep

> coming up. I will pursue this.

>

>