(Snigdha Mukerjee/Vanderbilt University)
The burning sensation you feel in your mouth when you sip alcohol has a name: oral chemesthesis. Understanding this sensation better could lead to new treatments for alcohol use disorders, but research in this area is scarce.
Vanderbilt Assistant Professor of Pharmacology Cody Siciliano aims to change that with his project, “Neural Mechanisms of Oral Chemesthesis,” which has been awarded a $1.3 million grant from the W.M. Keck Foundation.
“Cody Siciliano’s research on the neural mechanisms of chemical sensation in the mouth has the potential to revolutionize our understanding and treatment of alcohol use disorders,” said John Kuriyan, dean of the School of Medicine Basic Sciences. “This prestigious Keck Foundation grant is a well-deserved recognition of his innovative work in this critically important and underexplored area.
“We are proud to support Cody and his team as they conduct this transformative research that could offer new hope to millions affected by this devastating condition.”
Oral chemesthesis is caused by the chemical activation of nerve fibers in the mouth. “It’s not a taste; it’s a separate sensation that includes things like the burning from chili peppers or the cooling from menthol,” Siciliano said. The sensation can influence a wide range of behaviors, including the preference for spicy foods, avoidance of chemically contaminated food sources, and, most importantly for Siciliano’s research, attraction to alcoholic beverages.
Despite its significant behavioral impact, the brain mechanisms underlying oral chemesthesis remain largely unexplored—a PubMed search for “chemesthesis” returns less than 150 hits, nearly half of which are review articles, highlighting the scarcity of research in this area.
Not surprisingly, the concept for Siciliano’s project began over a drink. “Honestly, it was pretty organic,” he said. “I was having a mixed drink and just wondering, ‘How can you accurately detect alcohol in something that has several other ingredients in it?’ With alcohol, even the smallest amount in a drink, you can typically sense it right away.”
Siciliano’s research aims to uncover the sensory mechanisms that detect monohydroxy alcohols in the mouth and how these signals are interpreted by the brain to produce either attraction or avoidance of various alcohols based on their chemical structures.
“One thing that we’re going to try is to see if we can harness the chemesthetic system to control alcohol intake,” he said. “We’re making designer alcohol receptors to see if we can make a 5 percent (alcohol by volume) drink feel like a 50 percent one, with the aim to reduce alcohol consumption to more reasonable levels.”
With minimal existing research to guide him, Siciliano is pioneering new methods and exploring unfamiliar terrain in the human skull. “Getting the preliminary data for the application took quite a bit of time because the things we’re trying simply have not been tried before. Every step has involved adapting methods and mapping out unexplored areas, like the trigeminal ganglion,” which rests in the base of the skull and transmits sensory information from the mouth to the brain.
“We are hopeful that this will start a new field at the intersection of sensory and addiction sciences. Our work now can ultimately provide foundational research for future studies, whether by us or others,” Siciliano said.
Siciliano’s award marks the third Keck Foundation grant to Vanderbilt researchers since 2020. These accolades underscore Vanderbilt’s commitment to fostering transformative research that addresses critical scientific and medical challenges.
Research Development and Support, based in the Office of the Vice Provost for Research and Innovation, played a crucial role in the development of Siciliano’s proposal and interview preparation. RDS manages the Keck limited submission process throughout the year, which includes consultation calls with the Keck Foundation before submissions can be made.
“RDS was extremely helpful throughout the application process,” Siciliano said. “They have worked with the Keck Foundation successfully in the past and guided us every step of the way, from putting the application together to the virtual site visit.”
The W.M. Keck Foundation, established by Superior Oil Company founder William Myron Keck in 1954, is one of the nation’s largest philanthropic organizations. It supports outstanding science, engineering and medical research, along with undergraduate education and programs within Southern California that support arts and culture, education, health and community service projects.
