Photo: Raymond Quock, professor of pharmacology, observes effects of nitrous oxide in easing mouse’s anxiety. (Photo by Bob Hubner, WSU Photo Services.)
Deep in your brain are a myriad of lock-and-tumbler type systems that, when activated, trigger the production of substances that can reduce pain or help you to deal with anxiety. Raymond Quock, professor of pharmacology, and his staff are trying to gain a better understanding of these systems by looking for and testing various “keys” that can activate these processes.
Quock’s research is opening doors that allow his staff and others to explore how the brain and body work. His successes, and those of his colleagues throughout the nation, have changed the way pharmaceuticals are designed.
What that means to the average person is that prescription drugs are becoming more precise and safe, with fewer side effects.
Quock began research into how the brain and body work to overcome pain more than 20 years ago, when he was a professor of pharmacology at Marquette University’s School of Dentistry. One of the primary substances for his research was nitrous oxide (fondly known as laughing gas), which has been widely used among dentists to lessen patient discomfort.
“As a pharmacology instructor at a dental school, the relationship between pain relief, nitrous oxide and how the brain works was a natural research topic for me,” said Quock.
Spurring him on was a study published in the 1970s suggesting that nitrous oxide relieves pain by activating opioid receptors, similar to the way morphine, codeine and heroin turn on mechanisms in the brain that lessen pain. However, there was no documentation showing how nitrous oxide might make that happen.
Beginning in the early 1980s, Quock partnered with a succession of graduate students and research technicians, first at Marquette University, then the University of Illinois College of Medicine in Rockford, and now at WSU, to explore these brain mechanisms. They found that when laboratory mice inhale nitrous oxide, it stimulates their brains to produce and release elevated amounts of opioid peptides. These peptides, in turn, act like keys, unlocking or activating opioid receptors, which reduce pain in mice (and humans).
By measuring the levels of these peptides, found in the cerebrospinal fluid (CSF) of the mice, Quock and his associates became the first researchers to demonstrate that nitrous oxide indirectly activates opioid receptors through release of opioid peptides. Later studies identified the specific receptor subtypes that are responsible for nitrous oxide’s ability to relieve pain.
Quock’s research is currently funded via two grants from the National Institute on Drug Abuse (NIDA), one of 27 institutes and centers that comprise the National Institutes of Health (NIH).
One grant, for $192,000, is titled “Signaling Pathways for Benzodiazepine-Induced Behaviors.” This project compares the effects of nitrous oxide, benzodiazepine and cannabinoid (marijuana) drugs on behavior and reduction of anxiety.
The other grant, for $236,000, is titled “Genetic Control of Responsiveness to Nitrous Oxide Antinociception” and focuses on how nitrous oxide works to reduce pain and how genetics affects that process.
Although Quock’s studies use nitrous oxide, his research does not focus on the drug itself. The purpose of the research is to get a better understanding of how the brain works. Nitrous oxide is simply a tool that allows him to study brain functions.
“The brain has a lot of different, built-in mechanisms that regulate pain, temperature, blood pressure and other systems, and that control behavior,” he said. “The better we understand how the system works, the better we are able to develop new drugs that can turn on the system to relieve pain and anxiety from a variety of different points.
“What people once thought was a very simple, monolithic concept, is really much more complicated and heterogeneous. We now know there are a variety of both opioid peptides and opioid receptors that can interact in different ways. You might have a very specific drug that will activate or block just one type of receptor or you might have another drug that will activate or block a variety of receptors.”
Quock notes that his research capitalizes on results of the “Genome Project,” which is helping researchers all over the world better understand how the brain and body work.
“The more we understand how the brain and body work, the more researchers and manufacturers will be able to specifically design drugs that offer better pain relief, and that don’t pose addiction problems or possible side effects to the gastrointestinal tract, blood pressure or other systems,” he said.
And, to some degree, that’s already happening. Due to this kind of research, the entire approach to drug development is different than what it was 50 to 70 years ago.
“It used to be that pharmaceutical companies would come up with a new compound, then give it to a pharmacologist to see what it would do to the heart, kidney, brain,” he said. “But today, it’s no longer serendipitous. We focus on understanding how the brain, heart and other systems work. This knowledge, in turn, is used to better design drugs that target specific systems and minimize side effects.”
