Pain central. The RAIC area in the rat brain (red dot, top) contains nerve cells with receptors for GABA (bottom) that are thought to be crucial in pain control.

How Badly Will It Hurt?

There's a glimmer of hope on the horizon for some of the millions of people suffering from chronic pain with few effective options for treatment. A new study shows that the pain threshold can be heightened by manipulating a particular neurotransmitter, at least in rats.

Pain is clearly malleable. A patient's sensitivity can be altered by mood, attention, or direct stimulation of certain parts of the brain, for example. Figuring out how the brain perceives pain has proved difficult, as has treating chronic pain. So neurosurgeon Luc Jasmin of the University of California, San Francisco, and a team of scientists went looking for clues in the rostral agranular insular cortex (RAIC), a part of the brain that responds to sensations including physical pain. Jasmin's team lessened activity in the RAIC of rats by injecting a drug that blocks the enzyme that digests g-aminobutyric acid (GABA), a common neurotransmitter, thus raising GABA levels. Two hours after the injection, the rats could tolerate more heat on their paws before they started feeling pain. And when the team used a modified herpesvirus to deliver genes that make their brains produce more of the neurotransmitter, the effect lasted for up to 10 days, they report in the 17 July issue of the journal Nature.

The study suggests that the RAIC somehow controls the rats' perception of pain, Jasmin says. It could do so in two ways. The area is known to affect a pain-inhibition system that kicks in under extreme stress or trauma, such as an accident or attack, to temporarily suppress the sensation of pain, thereby allowing the victim to get to safety or fight back. The RAIC also has a connection with the amygdala, an area of the brain that is responsible for fear of and attention to pain. Jasmin says he hopes the same technique could raise the pain threshold for humans with chronic pain. "I'm very confident it will become available and widely used in the next decade," he says.

But neurobiologist Arthur Craig of the Barrow Neurological Institute in Phoenix, Arizona, says the jump from rats may not be easy, because the RAIC is far more developed in humans. "The RAIC is where we seem to feel pain, but it's not the only place that's important--there's a network," Craig says. "We don't know how it all works together yet, and that's key."

Related sites
Luc Jasmin's research
Barrow Neurological Institute