Researchers discover substance in brain that acts like the chemical that gives chilies their fire

by Kristen Cole

An international group of researchers led by a Brown graduate student recently identified a substance in the brain similar in structure and function to the active ingredient in hot chili peppers.

Although they do not yet know exactly what drives the body’s production of the compound, researchers think its release in tissues would likely cause burning pain, much like the sensation caused by the chemical capsaicin in chili peppers.

“Thirty years ago when people first realized that capsaicin acted this way they wondered if there was anything in the body that did the same,” said J. Michael Walker, Brown professor of psychology and neuroscience and a researcher who has long investigated the body’s neurochemical control of pain sensitivity. “We found it.”

Researchers described the substance, known as NADA for its chemical name N-arachidonoyldopamine, in the July issue of the Proceedings of the National Academy of Sciences. A related paper based on the research will be presented next month at the annual conference of the Society for Neuroscience.

Imagine the substance as part of a signaling network in the body, said Walker.

When a person eats spicy hot foods, the chemical capsaicin that has been introduced to the mouth activates a person’s pain fibers, causing the burning sensation. A molecule created within the body, an endogenous substance, with a similar structure would likely have the same painful effect, activating the same circuitry.

However, although capsaicin is introduced to the human body in the form of a food or topical medication, what causes NADA to be produced within the body is yet unclear, he said.

Researchers described NADA as being made up of two molecules common in the body. NADA easily binds to a receptor called vanilloid, or VR1, that is abundant in the body’s peripheral sensory fibers – those located in the nerves in the skin. The VR1 receptor is a protein that loops in and out of the cell membrane and responds to heat and acids.

In the study, NADA caused increased sensitivity to heat, meaning a lower threshold of what the body can tolerate, said lead researcher Susan M. Huang, a neuroscience graduate student.

For example, in a certain temperature range, water can feel warm without causing pain. Introducing NADA may lower the temperature people can tolerate, said Huang.

Further, the study found, NADA caused burning sensations in response to stimuli at much lower doses than capsaicin, said Walker.

Originally researchers thought the primary function for VR1 receptors would be for sensing heat outside the body – as indicated by the location of the receptors in the periphery of the body. An example of NADA at work in that case would be a burning feeling from an inflamed cut on the skin.

But the highest concentrations of NADA were found in three regions of the brain: the striatum, a region linked to motor control and reward; the hippocampus, a region that plays a role in memory and spatial relations; and the cerebellum, a region that coordinates movement and balance.

At this point, NADA’s function in the brain is just beginning to be explored. But when looking at the similar chemical in hot chili peppers, scientists know capsaicin affects the body beyond the burning pain at the site of contact. Consumption of hot chili peppers has secondary effects, such as an increase in body temperature and effects on the digestive system, said Walker.

Researchers also cite a common over-the-counter pain reliever that contains capsaicin. It first acts to cause the skin to feel painfully hot before it takes the pain away.

As with any substance integral to pain registration, being able to control the production and release of NADA may some day provide a way to control pain, said Walker.

The research was an international collaboration involving five laboratories in three countries throughout the year.

The Brown group began its search for the molecule after Italian scientist and paper co-author Vincenzo Di Marzo synthesized the compound in the laboratory and described its biological activity. Researchers hypothesized that the body may produce the compound because it is comprised of components made by the body.

Technology now exists to allow scientists to identify new molecules within months instead of years. “It’s always easier to find something when you have an idea of the chemical structure you are looking for,” said Huang.

However, she added, finding NADA in the body was difficult because of its chemical properties. Easily broken down, it is somewhat elusive to someone trying to track it down before it changes, she said.

The study was funded by grants from the National Institutes of Health, and the Ministero dell’Universitá e della Ricerca Scientifica e Tecnologica and the Associazione di Ricerca e Cura dell’Asma-Padua, with support from MDS/Sciex-Applied Biosystems, a company that manufactures high technology chemical analysis equipment.