Chemical Senses Vol. 30 No. suppl 1 © Oxford University
Press 2005; all rights reserved
Neural Correlates of Oral Irritation by Mustard Oil and other Pungent Chemicals: A Hot Topic
Section of Neurobiology, Physiology and Behavior, University of California, Davis, 1 Shields Avenue, Davis, CA 95616, USA
Correspondence to: E. Carstens, e-mail: eecarstens{at}ucdavis.edu
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Introduction |
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 Top Introduction AcknowledgementsReferences |
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Together with taste and smell, oral sensations of touch, temperature, chemical irritation and pain play an important role in determining food flavor. Trigeminal sensations are mediated by sensory fibers innervating the oral mucosa that project via the lingual nerve to reach the brainstem trigeminal complex, with extensive terminations in subnucleus caudalis (Vc) (Carstens et al., 1995
). Neurons in superficial laminae of dorsomedial Vc often
respond to a wide range of thermal, mechanical and irritant chemical stimuli (Carstens et al., 1998).
Different pungent chemicals elicit distinct temporal patterns of oral irritation.
Repetitive application of capsaicin elicits a progressive rise in irritancy
(sensitization;
Green, 1989), as do piperine and
concentrated salts and acids. In contrast, nicotine, menthol and cinnamaldehyde elicit
irritation that declines across trials (desensitization; for a review, see
Carstens et al., 2002). These
contrasting patterns are also observed in the responses of Vc neurons (Dessirier et al., 2000) and may depend
on the relative strength of opposing excitatory and desensitizing processes that are
initiated in trigeminal nerve endings by a particular irritant.
Recent molecular studies have uncovered the existence of six transient receptor
potential (TRP) channels that account for thermal sensations from extreme cold to extreme
heat (Jordt et al., 2003;
Montell, 2003). Several of these also
respond to irritant chemicals. Thus, TRPV1 (VR-1) is activated by noxious heat and
capsaicin (Caterina et al.,
1997), TRPM8 (CMR-1) by cooling and menthol (McKemy et al., 2002;
Peier et al., 2002) and
TRPA1 (ANKTM1) by intense cold, mustard oil, cinnamaldehyde, cannabinoids and other
chemicals (Story et al.,
2003;
Bandell et al., 2004;
Jordt et al., 2004). Our
laboratory is particularly interested in the sensory properties of mustard oil in
relation to TRPA1.
In psychophysical experiments, lingual application of mustard oil (allyl
isothiocyanate, 0.125%) elicited a desensitizing pattern of oral irritation and
exhibited mutual cross-desensitization with capsaicin (Simons et al., 2003). Mustard oil similarly
elicited a desensitizing firing pattern in Vc neurons recorded in anesthetized rats and
cross-desensitized responses to pentanoic acid (Simons et al., 2004). However, mustard oil
(1.25%) sensitized Vc responses to noxious heat, consistent with its well-known
sensitizing effect on the skin. These contrasting effects of mustard oil (i.e. heat
sensitization and chemical desensitization) are not consistent with peripheral or central
sensitization, but might reflect a TRPA1-mediated enhancement of thermal gating of TRPV1
and an inhibition of chemical gating of TRPV1 (or other channels) co-expressed in the
same trigeminal nerve endings.
TRPA1 is activated by intense cold, mustard oil and cinnamaldehyde (Bandell et al., 2004) and we routinely
record from Vc neurons that respond to these stimuli as well as to noxious heat and
capsaicin (but not menthol). An example is shown in Figure
1. TRPA1 exhibits desensitization to
repeated cooling (Story et al.,
2003). We observed a significant decline in successive responses of Vc
neurons to repeated lingual cooling (3°C) at rapid (15 s) intervals (Figure
2A,C). Vc responses usually also
exhibited desensitization to repeated application of mustard oil or cinnamaldehyde
(Figure
2B). Moreover, cold-evoked responses
were significantly reduced following application of mustard oil or cinnamaldehyde (Figure
2B,D), suggesting a TRPA1 chemically
mediated cross-desensitization of thermal gating of TRPA1.
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In conclusion, a substantial population of Vc neurons receives input from trigeminal afferents expressing TRPA1 and/or TRPV1, with some properties of TRPA1 being reflected in the responses of Vc neurons. It is curious that mustard oil, associated with a burning quality and intense cold, both apparently act via a common transduction mechanism. It is additionally puzzling as to how the nervous system can make qualitative discriminations based on input from neurons that respond to both noxious hot and cold stimuli. Nevertheless, the discovery of thermo- and chemosensitive TRP channels has certainly spiced up the field of trigeminal chemoreception.
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Acknowledgements |
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TopIntroductionAcknowledgementsReferences |
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Supported by NIH (DE 13685) and the California Tobacco-related Disease Research Program (No. 11RT-0053).
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References |
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TopIntroductionAcknowledgementsReferences |
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