|Irritating Smells Alert Special Cells, NIH-Funded
If you cook, you know. Chop an onion and you risk crying over
your cutting board as a burning sensation overwhelms your eyes
and nose. Scientists do not know why certain chemical odors, like
onion, ammonia and paint thinner, are so highly irritating, but
new research in mice has uncovered an unexpected role for specific
nasal cavity cells. Researchers funded by the National Institute
on Deafness and Other Communication Disorders (NIDCD), part of
the National Institutes of Health, describe this work in the March
issue of the Journal of Neurophysiology, now available
Weihong Lin, Ph.D., of the University of Colorado Denver School
of Medicine and University of Maryland, Baltimore County, led the
study which discovered that a particular cell, abundant near the
entry of many animal noses, plays a crucial and previously unknown
role in transmitting irritating and potentially dangerous odors.
Dr. Lin and colleagues from both universities plus the Mount Sinai
School of Medicine identified the role of this solitary chemosensory
cell in transmitting irritating chemical odors in the noses of
Scientists have found similar solitary chemosensory cells in the
nasal cavities, airways and gastrointestinal tracts of many mammals
as well as fish, frogs and alligators; they think it is likely
that they are also present in humans, explains Thomas Finger, Ph.D.,
one of the senior co-authors at the University of Colorado Denver.
Prior to this work, scientists who study smell and taste thought
that irritating odors directly stimulated the trigeminal nerve,
which senses touch, temperature and pain throughout the head region,
including the delicate membranes that line the inside of the nose.
The research team, under the guidance of Diego Restrepo, Ph.D.,
found that solitary chemosensory cells scattered in the epithelium
inside the front of the nose respond to high levels of irritating
odors and relay signals to trigeminal nerve fibers.
"This elegant research corrects an erroneous assumption about
how irritating odors are perceived and expands our understanding
of olfaction," says James F. Battey, M.D., Ph.D., director
of NIDCD. "With further investigation, it also might lead
to a better understanding of why some people are exceptionally
sensitive to irritating odors."
Solitary chemosensory cells on the surface of the nasal cavity
are in close contact with trigeminal nerve fibers which end just
below the surface. Earlier research revealed that these cells contain
bitter taste receptors and that bitter substances applied to the
surface of the nasal cavity trigger a trigeminal nerve response.
Intrigued, Drs. Restrepo and Finger decided to explore whether
solitary chemosensory cells respond to irritating odors. Using
nasal tissue from mice, the scientists measured a variety of changes
in solitary chemosensory cells as they exposed the cells to low
and high levels of several irritating, volatile chemical odors.
Among their observations were changes in electrical activity in
the cells — which indicates a response to an outside stimulus — and
changes in intracellular calcium ion concentration — which
indicates signaling to other cells. Their measurements demonstrated
that the solitary chemosensory cells responded to the odors and
relayed sensory information to trigeminal nerve fibers.
Once stimulated, the trigeminal nerve will convey pain and burning
sensations and can trigger protective reflexes such as gagging
and coughing. The architecture of nasal tissue with solitary chemosensory
cells on the surface and trigeminal nerve fibers just below allows
the nose to detect a greater number of irritating odors, the scientists
Fortunately, the threshold for triggering a response is high,
so exposure to a small amount of an irritating chemical, as might
naturally emanate from some kinds of fresh fruit, will not bring
on gagging and coughing. For example, lemons contain the volatile
chemicals citral and geraniol but at levels too low to trigger
a trigeminal response. Only high, potentially dangerous levels
of odors will trigger the protective gagging-and-coughing response.
The researchers point out that their findings provide an example
of the Law of Specific Nerve Energies, conceived by Johannes Peter
Muller in 1826. Muller said that the way we perceive a stimulus
depends on the nerve or sensory system that conveys it rather than
the physical nature of the stimulus itself. In the case of irritating
odors, we perceive them as irritating because they are transmitted
via the trigeminal nerve, leading the brain to interpret the message
as pain rather than as a smell.
The researchers say their findings raise new questions about how
irritating odors are detected. They say more research is needed
to explore whether solitary chemosensory cells are programmed to
recognize specific irritants, which receptors are involved, and
what steps a solitary chemosensory cell uses to convert a chemical
stimulus to a signal it relays to the trigeminal nerve.
The NIDCD supports and conducts research and research training
on the normal and disordered processes of hearing, balance, smell,
taste, voice, speech and language and provides health information,
based upon scientific discovery, to the public. For more information
about NIDCD programs, see the Web site at www.nidcd.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.