New Insights into Pain Regulation and Therapy

The results were published in the July 17 issue of Nature.

Researchers focused on a small region of the cerebral cortex known as the rostral agranular insular cortex (RAIC), one of the cortical areas consistently activated by painful stimuli. Since GABA is prolific in RAIC, they reasoned that changing levels of GABA could show how RAIC might regulate pain. When they increased levels of GABA throughout RAIC in normal rats, the animals displayed a clear and consistent analgesia. When the increase was sustained by injecting a gene (GAD 67) into neuronal and glial cells that encodes an enzyme that synthesizes GABA, the analgesia lasted up to 10 days. That suggested that GABA works through neural mechanisms that do not down-regulate over time.

When the researchers blocked transmission of signals through the descending pain inhibitory system, which extends from the RAIC to the spinal cord, the analgesic effect was reversed, indicating that GABA works partly through this system to enhance the inhibition of neurons that incite pain. Finding that a large number of RAIC neurons expressing GABA-B receptors project to the amygdala, they explored GABA's role in this pathway. After GABA was increased in the RAIC, GABA-B-bearing RAIC neurons that projected to the amygdala were selectively disinhibited. As a result, the rats experienced pain. When the activation was reversed, the pain was abolished.

"This finding demonstrates that the change in pain level works through two separate systems, with opposite effects,” said senior author Peter O'Hara, Ph.D., associate professor of anatomy at the University of California, San Francisco (USA; www.ucsf.edu). "This dual effect is probably a defining feature of pain modulation, and we speculate that an imbalance in the cortical output is likely to underlie some chronic pain states.”




Related Links:
University of California, San Francisco