Learning Objectives
By the end of this section, you should be able to
- 8.4.1 Define the sense of chemesthesis with examples.
- 8.4.2 Describe the role of the somatosensory system and TRP channels in producing sensations we commonly refer to as spicy.
- 8.4.3 Describe the role that solitary chemosensory cells and airway taste receptors play in protecting the vertebrate airway.
Imagine being served a hot bowl of chili after spending a snowy winter day outside; as you are handed the steaming bowl, it warms your icy hands. The aroma of the heavily spiced dish is mouthwatering, but it is likely at a scalding temperature. So, you take the time to let a spoonful cool before eating. The savory dish is just what the day calls for but as you chew the slightly warm spoonful of chili, your mouth starts burning. You quickly reach for a glass of water to quench the sensation only to find temporary relief. You now recognize this burning sensation has nothing to do with the temperature of the food but rather chemicals from the chili plants that give this dish its name. In this section, you will learn how some chemicals create the sensation of cooling and warmth that influence our perception of flavor and play an important role in innate immunity.
The somatosensory system plays a role in flavor perception
The primary role of the somatosensory system is to detect kinetic and thermal energy (see Chapter 9 Touch and Pain), but somatosensory neurons are also capable of responding to chemicals. In most parts of the vertebrate body, these sensory neurons are protected from the environment by skin; however, where these neurons innervate the mucous membranes (e.g. eyes, mouth, airway, digestive, and reproductive tracts) or when skin is damaged, chemicals are granted access to the underlying free nerve endings. When chemicals activate somatosensory nerves, you experience sensations that are described as burning, cooling, stinging, irritating or pungent.
The capacity of the somatosensory system to detect these chemicals is referred to as chemesthesis. When neuroscientists were initially studying these sensations, it was not clear what neural subsystem was responsible for them. Thus, the term common chemical sense was long used to describe the seemingly ubiquitous ability of tissues to detect chemicals like capsaicin (the “hot” chemical found in chili peppers) or low pH solutions. Once experimental evidence mounted to suggest that these sensations were entirely mediated by the somatosensory system, the term chemesthesis was suggested to distinguish between the more typical stimulation of the somatosensory system with kinetic and heat energy—referred to as somesthesis. Both somesthesis and chemesthesis contribute to flavor, but, of the two, chemesthesis is more often confounded with the sense of “taste.”
Chemesthetic chemicals make a substantial contribution to the flavor of many foods we eat. Nearly all the cooking ingredients we refer to as seasonings or spices (the obvious exception being salt) have been cultivated because they contain chemicals that selectively activate receptors on somatosensory neurons. The neurophysiological properties of these chemicals are so sought after that nations have been drawn into economic, political, and military conflicts over access to their botanical sources.
Scientists that study chemesthesis have noted that it seems counterintuitive for humans to seek out these chemicals. Most chemesthetic chemicals produce sensation by activating polymodal nociceptors: small diameter free nerve endings that respond to stimuli as different as plant metabolites, low pH, and heat energy. The stimulation of this neuron produces noxious or painful sensations. Most animals avoid substances that stimulate polymodal nociceptors and even humans that willingly consume spices often describe the sensation as painful.
Many hypotheses have been formulated to explain why some humans enjoy spicy foods. Most of them center around chemesthetic chemicals providing some health benefit; improved secretion of digestive enzymes, enhanced thermoregulation, and antimicrobial resistance have all been suggested. One popular theory asserts that individuals learn to enjoy spicy foods because the noxious sensations cause the release of endogenous opioids. Several studies have presented data that the opioid antagonist naloxone decreases the preference for spicy foods as support for this theory. However, a preference for heavily spiced food is highly correlated with sensation and novelty seeking personality traits, and naloxone also blunts the enjoyment of other activities enjoyed by individuals that seek out novel sensations and do not directly involve noxious somatosensation, like gambling. Thus, the novelty or the intensity of spicy chemicals are more likely responsible for the involvement of the opioid system than any direct link with the noxious sensation produced by chemesthetic chemicals.
Thermal TRPs
Most chemicals that have chemesthetic properties selectively activate members of the Transient Receptor Potential (TRP) channel gene super family (Figure 8.19). TRP channels are ubiquitous in sensory systems, but several members of the family are activated at low or high temperatures. These thermal-TRPs are differentially expressed by sensory cells that allow animals to discriminate between different temperatures. Some of the thermal-TRPs are expressed by polymodal nociceptors; much of the polymodal capacity of these nerve fibers is due to the many different stimuli that can activate an individual TRP channel and the co-expression of multiple TRP channel family members on these free nerve endings.
The most well-known chemical with chemesthetic properties is capsaicin, which is produced by chili peppers and related plants. Most mammals perceive capsaicin as noxiously hot because it activates TRP Vanilloid 1 (TRPV1) channels present on small-diameter peptidergic polymodal nociceptors (c-fibers). A similar channel, TRP ankyrin 1 (TRPA1), is found on a subset of these neurons and is activated by allyl isothiocyanate (AITC), which is the pungent compound in mustard plants, like horseradish and wasabi. Menthol, the cooling compound in mint, activates TRP Melastatin 8 (TRPM8) which is found on different nerve fibers that respond to cold. Many chemical compounds produced by plants are capable of shaping human and animal behavior because of their ability to interact with the receptors of the somatosensory system.
Solitary chemosensory cells
The most common chemesthetic compounds are lipophilic and pass-through epithelial cells to stimulate the underlying nerves, but some stimulate somatosensory nerves indirectly though specialized epithelial cells. These neuro-epithelial cells have a microvillar brush or tuft projecting apically, resembling isolated taste receptor cells morphologically. Due to these cells being identified by independent research groups in a variety of tissues, they have alternatively been called tufted cells, microvillar cells, neuroendocrine cells, brush cells or solitary chemosensory cells (SCCs). They can be seen diagrammed as SCCs in Figure 8.20.
SCCs form synapses with polymodal nociceptive fibers of the somatosensory system (shown as a pain nerve fiber contacting the SCC in Figure 8.20). This anatomical arrangement allows for SCCs to monitor the lumen of organs for chemicals that would not normally be detected by the nervous system.
SCCs have been identified in many hollow organs at risk of bacterial infection—from the nose, trachea, eustachian tube (middle ear), tear duct, periodontium (tooth socket), and the urinary bladder. The SCCs in the respiratory epithelium of the nose and trachea have been best characterized. In the airway, these cells appear to resemble bitter-sensitive type II taste receptor cells. These cells respond to traditionally bitter compounds, but, more remarkably, are also stimulated by a class of chemicals produced by reproducing gram negative bacteria, called acyl-homoserine lactones (AHLs). This allows SCCs to act as sentinels of epithelial tissues, monitoring the apical surface of epithelium for potentially dangerous bacterial infections.
When SCCs detect a growing bacterial infection, they trigger local epithelial defenses, recruit an immune response, and activate polymodal nociceptive nerve fibers. SCCs form synapses with nerves (Figure 8.20) and on stimulation release the neurotransmitter acetylcholine (ACh) to activate those nerves. Activation of nociceptors in the airway results in the local and central release of pro-inflammatory neuropeptides, which further sensitize the airway and recruit an immune response (see Chapter 9 Touch and Pain). More immediately, stimulation of airway polymodal nociceptors produces sensations of burning and stereotyped changes to the respiratory rhythm that we commonly call sneezing and coughing. Mice that have had SCC signaling disrupted spend more time in chambers with nebulized bitter chemicals than controls (Xi et al., 2023). Sneezing and coughing are behaviors that ultimately increase the velocity air is expelled from the airway making it more likely that microorganisms are dislodged and expelled. SCCs are responsible for generating a response to invading microbes on the tissue level and triggering behaviors that together guard against airway pathogens.