Researchers discover mechanism involved in chronic pain

Zizhen Zhang

Zizhen Zhang

Chronic pain is one of the most common reasons people visit their doctor, and basic scientists have long been trying to understand it. In Canada, chronic pain costs more than heart disease, HIV and cancer combined. New animal research, published online in Cell Reports on July 23, out of the Cumming School of Medicine has made a discovery that provides more insight into the mechanisms of pain.

Pain is an unpleasant feeling caused by intense or damaging stimuli. It can be classified as being either physical (due to injury at a definitive location on the body, also known as the periphery), or emotional (such as sadness).

“We wanted to understand how pain signals are transmitted from the periphery to the central nervous system, and how nerve signals are processed in higher brain centres such as the prefrontal cortex (PFC),” says Zizhen Zhang, PhD, lead author on the study. “We demonstrated that during nerve injury, there is reduced neural activity in the principal cells of the prelimbic cortex in animal models, which corresponds to the PFC in humans,” explains Zhang, a research associate in the lab of the Gerald Zamponi, PhD, and member of the Alberta Children’s Hospital Research Institute and Hotchkiss Brain Institute (HBI).

The PFC, which sits directly behind the forehead, plays an important role in pain perception and provides top down control of sensory and emotional pain processing. To study this region of the brain, researchers used a technique called optogenetics – using light-based tools to target neurons that are genetically altered to be light-sensitive.

Use of optogenetic technologies was made possible by the HBI Advanced Light and Optogenetics (HALO) initiative. Launched in 2011 to support the establishment of optogenetics research in the Institute, the HALO facility continues to expand its capacity and expertise.

Using animal models, the researchers used optogenetics to either excite or inhibit neurons to simulate or inhibit pain responses. The team used a blue laser to activate neurons to stimulate a pain perception, and used a yellow light to inhibit these neurons, and thereby reduce pain perception. By doing this, they discovered that the low neural activity in the PFC is caused by the enhancement of an inhibitory circuit. Researchers believe that this pathway could one day be used as a target to inhibit the perception of pain.

Zizhen says there is still further research to be done so they can understand this new mechanism in greater detail. But in the long term, he hopes the discovery will eventually lead to non-invasive treatments for pain management.

“Imagine in the future, if we were able to reduce pain using laser light manipulation.”

Additional contributors to this research include: Vinicius De Maria Gadotti, PhD, Lina Chen, Ivana Assis Souza, PhD, Patrick L. Stemkowski,PhD, and Gerald W. Zamponi, PhD.

Source of text and photo: Hotchkiss Brain Institute

Photo credit: Photo by Bruce Perrault

Original Research Article:

Zhang Z, Gadotti VM, Chen L, Souza IA, Stemkowski PL, Zamponi GW. Role of Prelimbic GABAergic Circuits in Sensory and Emotional Aspects of Neuropathic Pain. Cell Rep. 2015 Aug 4;12(5):752-9. doi: 10.1016/j.celrep.2015.07.001. Epub 2015 Jul 23.