pág. 3535
TRPV1 AS A MOLECULAR TARGET FOR
THERAPEUTIC INTERVENTIONS IN
STOMATOLOGY
TRPV1 COMO DIANA MOLECULAR PARA INTERVENCIONES
TERAPÉUTICAS EN ESTOMATOLOGÍA
Paloma Montserrat Rosas Licona
Facultad de Ciencias Químicas de la Benemérita Universidad Autónoma de Puebla
Ana Delia Licona Ibarra
Clínica de Ortodoncia y Ortopedia Maxilar- Puebla de Zaragoza
Aurora Linares Campos
Facultad de Ciencias Químicas de la Benemérita Universidad Autónoma de Puebla
Laura Morales Lara
Facultad de Ciencias Químicas de la Benemérita Universidad Autónoma de Puebla
Victorino Gilberto Serafín Alatriste Bueno
Facultad de Ciencias Químicas de la Benemérita Universidad Autónoma de Puebla
pág. 3536
DOI: https://doi.org/10.37811/cl_rcm.v9i2.17156
TRPV1 as a molecular target for therapeutic interventions in stomatology
Paloma Montserrat Rosas Licona1
rosaspaloma122@gmail.com
https://orcid.org/0009-0001-0025-4444
Facultad de Ciencias Químicas de la Benemérita
Universidad Autónoma de Puebla
México
Ana Delia Licona Ibarra
analiconaibarra@hotmail.com
https://orcid.org/0009-0000-5507-8532
Clínica de Ortodoncia y Ortopedia Maxilar-
Puebla de Zaragoza
México
Aurora Linares Campos
alinares_campos@hotmail.com
https://orcid.org/0009-0001-5774-5869
Facultad de Ciencias Químicas de la Benemérita
Universidad Autónoma de Puebla
México
Laura Morales Lara
laura.morales@correo.buap.mx
https://orcid.org/0000-0001-5404-754X
Facultad de Ciencias Químicas de la Benemérita
Universidad Autónoma de Puebla
México
Victorino Gilberto Serafín Alatriste Bueno
victorino.alatriste@correo.buap.mx
https://orcid.org/0000-0001-8680-5018
Facultad de Ciencias Químicas de la Benemérita
Universidad Autónoma de Puebla
México
ABSTRACT
Transient receptor potential vanilloid 1 (TRPV1) is a cation channel involved in sensory perception in
various tissues, including the oral cavity. This review article addresses its distribution in structures such
as dental components, the oral mucosa, the trigeminal nerve, the tongue, and the salivary glands,
highlighting its role in the modulation of nociception and inflammation. It also participates in tissue
homeostasis and the response to chemical or thermal stimuli in oral physiology. Likewise, its role in
various oral conditions, such as dentin hypersensitivity and oral squamous cell carcinoma, is analyzed
since TRPV1 overexpression is associated with tumor progression. On the other hand, in the context of
COVID-19, the possible relationship between TRPV1 and sensory alterations linked to the viral
infection is discussed. Finally, therapeutic strategies based on the modulation of this receptor with enafis
are addressed in the use of agonists and antagonists for the control of orofacial pain and the improvement
of pathological conditions in the oral cavity.
Keywords: trpv1, oral cavity, sensitivity, nociception
1 Autor principal
Correspondencia: rosaspaloma122@gmail.com
DOI: https://doi.org/10.37811/cl_rcm.v9i2.17156
TRPV1 as a molecular target for therapeutic interventions in stomatology
Paloma Montserrat Rosas Licona1
rosaspaloma122@gmail.com
https://orcid.org/0009-0001-0025-4444
Facultad de Ciencias Químicas de la Benemérita
Universidad Autónoma de Puebla
México
Ana Delia Licona Ibarra
analiconaibarra@hotmail.com
https://orcid.org/0009-0000-5507-8532
Clínica de Ortodoncia y Ortopedia Maxilar-
Puebla de Zaragoza
México
Aurora Linares Campos
alinares_campos@hotmail.com
https://orcid.org/0009-0001-5774-5869
Facultad de Ciencias Químicas de la Benemérita
Universidad Autónoma de Puebla
México
Laura Morales Lara
laura.morales@correo.buap.mx
https://orcid.org/0000-0001-5404-754X
Facultad de Ciencias Químicas de la Benemérita
Universidad Autónoma de Puebla
México
Victorino Gilberto Serafín Alatriste Bueno
victorino.alatriste@correo.buap.mx
https://orcid.org/0000-0001-8680-5018
Facultad de Ciencias Químicas de la Benemérita
Universidad Autónoma de Puebla
México
ABSTRACT
Transient receptor potential vanilloid 1 (TRPV1) is a cation channel involved in sensory perception in
various tissues, including the oral cavity. This review article addresses its distribution in structures such
as dental components, the oral mucosa, the trigeminal nerve, the tongue, and the salivary glands,
highlighting its role in the modulation of nociception and inflammation. It also participates in tissue
homeostasis and the response to chemical or thermal stimuli in oral physiology. Likewise, its role in
various oral conditions, such as dentin hypersensitivity and oral squamous cell carcinoma, is analyzed
since TRPV1 overexpression is associated with tumor progression. On the other hand, in the context of
COVID-19, the possible relationship between TRPV1 and sensory alterations linked to the viral
infection is discussed. Finally, therapeutic strategies based on the modulation of this receptor with enafis
are addressed in the use of agonists and antagonists for the control of orofacial pain and the improvement
of pathological conditions in the oral cavity.
Keywords: trpv1, oral cavity, sensitivity, nociception
1 Autor principal
Correspondencia: rosaspaloma122@gmail.com
pág. 3537
TRPV1 como diana molecular para intervenciones terapéuticas en
estomatología
RESUMEN
El receptor de potencial transitorio vanilloide 1 (TRPV1) es un canal cationico involucrado en la
percepción sensorial en diversos tejidos, incluidos aquellos que constituyen a la cavidad oral. Este
artículo de revisión aborda su distribución en estructuras como los componentes dentales, la mucosa
bucal, el nervio trigemino, la lengua y las glándulas salivales, resaltando su papel en la modulación de
la nocicepción e inflamación. Así como su participación en la homeostasis tisular y la respuesta a
estímulos químicos o térmicos en la fisiología oral. De igual forma, se analiza su papel en diversas
afecciones orales, como la hipersensibilidad dentinaria y el carcinoma oral de células escamosas, puesto
que la sobreexpresión a TRPV1 se asocia con la progresión tumoral. Por otro lado, en el contexto del
COVID19, se discute la posible relación entre TRPV1 y alteraciones sensoriales vinculadas a la
infeccion viral. Finalmente, se abordan estrategias terapéuticas basadas en la modulación de este
receptor con enafis en el uso de agonistas y antagonistas para el control del dolor orofacial y la mejora
de condiciones patológicas en la cavidad oral.
Palabras clave: trpv1, cavidad oral, sensibilidad, nocicepción
Artículo recibido 15 enero 2025
Aceptado para publicación: 19 febrero 2025
TRPV1 como diana molecular para intervenciones terapéuticas en
estomatología
RESUMEN
El receptor de potencial transitorio vanilloide 1 (TRPV1) es un canal cationico involucrado en la
percepción sensorial en diversos tejidos, incluidos aquellos que constituyen a la cavidad oral. Este
artículo de revisión aborda su distribución en estructuras como los componentes dentales, la mucosa
bucal, el nervio trigemino, la lengua y las glándulas salivales, resaltando su papel en la modulación de
la nocicepción e inflamación. Así como su participación en la homeostasis tisular y la respuesta a
estímulos químicos o térmicos en la fisiología oral. De igual forma, se analiza su papel en diversas
afecciones orales, como la hipersensibilidad dentinaria y el carcinoma oral de células escamosas, puesto
que la sobreexpresión a TRPV1 se asocia con la progresión tumoral. Por otro lado, en el contexto del
COVID19, se discute la posible relación entre TRPV1 y alteraciones sensoriales vinculadas a la
infeccion viral. Finalmente, se abordan estrategias terapéuticas basadas en la modulación de este
receptor con enafis en el uso de agonistas y antagonistas para el control del dolor orofacial y la mejora
de condiciones patológicas en la cavidad oral.
Palabras clave: trpv1, cavidad oral, sensibilidad, nocicepción
Artículo recibido 15 enero 2025
Aceptado para publicación: 19 febrero 2025
pág. 3538
INTRODUCTION
Transient receptor potential (TRP) constitutes a superfamily of specialized proteins that comprise more
than 30 subtypes in mammals (Chen et al., 2024). Its primary function is modulating membrane potential
by increasing intracellular ion concentrations (Samanta et al., 2018). They act as integrators of
polymodal signals, responding to various environmental and physiological stimuli (Chen et al., 2024).
Considering the homology in their amino acid sequences, their structural characteristics, and the ligands
with which they interact, mammalian TRP proteins are grouped into six main subfamilies (TRPC,
TRPM, TRPA, TRPML, TRPP, and TRPV) as shown in Table 1.
Table 1. General classification of the mammalian TRP channel superfamily.
Subfamily Name Isoforms Function
TRPC Canonical 1-7 They are non-voltage-regulated channels that allow
the entry of Ca2+ and Na+ in response to PIP₂ and IP₃.
They contribute to cell signaling, proliferation, and
neuronal and muscle modulation (Wen et al., 2020).
TRPM Melastatin 1-8 They mediate the influx of Ca²⁺ and Mg²⁺ in response
to changes in ion and lipid concentrations. It detects
oxidative stress, endothelial permeability, and
vascular tone (Huang et al., 2020).
TRPML Mucolipin 1-3 They adjust the autophagy-lysosome system,
influencing cancer progression and immune evasion
(Santoni et al., 2020).
TRPA Ankyrin 1 It is in the dorsal root ganglia and trigeminal nerves.
It has ankyrin repeats and is activated by extreme cold
and electrophilic or non-covalent compounds (Nilius
et al., 2012).
INTRODUCTION
Transient receptor potential (TRP) constitutes a superfamily of specialized proteins that comprise more
than 30 subtypes in mammals (Chen et al., 2024). Its primary function is modulating membrane potential
by increasing intracellular ion concentrations (Samanta et al., 2018). They act as integrators of
polymodal signals, responding to various environmental and physiological stimuli (Chen et al., 2024).
Considering the homology in their amino acid sequences, their structural characteristics, and the ligands
with which they interact, mammalian TRP proteins are grouped into six main subfamilies (TRPC,
TRPM, TRPA, TRPML, TRPP, and TRPV) as shown in Table 1.
Table 1. General classification of the mammalian TRP channel superfamily.
Subfamily Name Isoforms Function
TRPC Canonical 1-7 They are non-voltage-regulated channels that allow
the entry of Ca2+ and Na+ in response to PIP₂ and IP₃.
They contribute to cell signaling, proliferation, and
neuronal and muscle modulation (Wen et al., 2020).
TRPM Melastatin 1-8 They mediate the influx of Ca²⁺ and Mg²⁺ in response
to changes in ion and lipid concentrations. It detects
oxidative stress, endothelial permeability, and
vascular tone (Huang et al., 2020).
TRPML Mucolipin 1-3 They adjust the autophagy-lysosome system,
influencing cancer progression and immune evasion
(Santoni et al., 2020).
TRPA Ankyrin 1 It is in the dorsal root ganglia and trigeminal nerves.
It has ankyrin repeats and is activated by extreme cold
and electrophilic or non-covalent compounds (Nilius
et al., 2012).
pág. 3539
TRPP Polycystin 2, 3 y 5 They form complexes with polycystins, and their
dysfunction is related to autosomal dominant
polycystic kidney disease (Semmo et al., 2014).
TRPV Vanilloids 1-4 They interact with vanilloid compounds and respond
to temperature increases and pH changes. They play
a key role in nociception (Zhang et al., 2023).
Among the TRP protein subfamilies, transient receptors potential vanilloid (TRPV), particularly
TRPV1, stand out for their relevance in detecting noxious stimuli and their fundamental role in specific
physiological processes. TRPV1 comprises intracellular N-terminal and C-terminal regions and a
transmembrane region, which includes six domains (S1-S6) that form the channel pore (Nadezhdin et
al., 2021). Its activation allows the entry of Ca²⁺ into the cell, which causes membrane depolarization or
starts signaling pathways (Zhang et al., 2023). While S5 and S6 are crucial for pore opening (Nadezhdin
et al., 2021), the TRP domain, located after S6, is critical to subunit assembly and allosteric modulation
of the channel (Liao et al., 2013).
This receptor opens its cationic pore to enter Ca2+ by interacting with ligands. The most studied
exogenous agonist for TRPV1 is capsaicin, the active ingredient in chili peppers (genus Capsicum)
(Yang & Zheng, 2017). Likewise, it interacts with other organic molecules such as piperine (bioactive
from pepper), cinnamodial (unsaturated dialdehyde terpenes, located in cinnamon), allicin (derived from
garlic), monoterpenes such as eugenol (derived from eucalyptus), phytocannabinoids, myrcene and
camphor (Andrei et al., 2023).
To open their channel, TRPV1 also uses endogenous inflammatory mediators, such as anandamide and
arachidonic acid metabolites (Elokely et al., 2016), and thermal stimulation. Molecular dynamics
simulations show that TRPV1 remains closed at 30°C with a stable lower gate, while at 60°C, it
undergoes changes that stimulate the channel (Zheng & Wen, 2019). This process can be modulated by
divalent cations, which reduce the activation temperature by inducing structural changes in the
extracellular region (Andrei et al., 2023). On the other hand, TRPV1 detects pH deviations with opening
promotion, implying a proton permeation mechanism that can occur even in the presence of
TRPP Polycystin 2, 3 y 5 They form complexes with polycystins, and their
dysfunction is related to autosomal dominant
polycystic kidney disease (Semmo et al., 2014).
TRPV Vanilloids 1-4 They interact with vanilloid compounds and respond
to temperature increases and pH changes. They play
a key role in nociception (Zhang et al., 2023).
Among the TRP protein subfamilies, transient receptors potential vanilloid (TRPV), particularly
TRPV1, stand out for their relevance in detecting noxious stimuli and their fundamental role in specific
physiological processes. TRPV1 comprises intracellular N-terminal and C-terminal regions and a
transmembrane region, which includes six domains (S1-S6) that form the channel pore (Nadezhdin et
al., 2021). Its activation allows the entry of Ca²⁺ into the cell, which causes membrane depolarization or
starts signaling pathways (Zhang et al., 2023). While S5 and S6 are crucial for pore opening (Nadezhdin
et al., 2021), the TRP domain, located after S6, is critical to subunit assembly and allosteric modulation
of the channel (Liao et al., 2013).
This receptor opens its cationic pore to enter Ca2+ by interacting with ligands. The most studied
exogenous agonist for TRPV1 is capsaicin, the active ingredient in chili peppers (genus Capsicum)
(Yang & Zheng, 2017). Likewise, it interacts with other organic molecules such as piperine (bioactive
from pepper), cinnamodial (unsaturated dialdehyde terpenes, located in cinnamon), allicin (derived from
garlic), monoterpenes such as eugenol (derived from eucalyptus), phytocannabinoids, myrcene and
camphor (Andrei et al., 2023).
To open their channel, TRPV1 also uses endogenous inflammatory mediators, such as anandamide and
arachidonic acid metabolites (Elokely et al., 2016), and thermal stimulation. Molecular dynamics
simulations show that TRPV1 remains closed at 30°C with a stable lower gate, while at 60°C, it
undergoes changes that stimulate the channel (Zheng & Wen, 2019). This process can be modulated by
divalent cations, which reduce the activation temperature by inducing structural changes in the
extracellular region (Andrei et al., 2023). On the other hand, TRPV1 detects pH deviations with opening
promotion, implying a proton permeation mechanism that can occur even in the presence of
pág. 3540
physiological concentrations of Na+, Mg2+, and Ca2+ (Hellwig et al., 2004) due to a hydrophilic bridge
that allows proton conductance and cation permeation (Hellwig et al., 2004).
TRPV1 was initially identified in thinly myelinated and unmyelinated slow-conducting primary
somatosensory afferent neurons of the dorsal root ganglia of the spinal cord (Andresen, 2019). However,
subsequent research has shown that this receptor is widely distributed in other body cell types and
tissues. It is essential to address its role in regions sensitive to stimuli that affect the receptor, such as
the oral cavity. In this area, TRPV1 is in sensory afferent nerve fibers, such as Aδ and C fibers (Smutzer
& Devassy, 2016). Furthermore, it is widely distributed in oral epithelial cells, where it plays a key role
in the inflammatory response and the regulation of local homeostasis (Moayedi et al., 2022). It has even
been reported that in keratinocytes, TRPV1 contributes to sensory perception and the modulation of the
immune system (Smutzer & Devassy, 2016).
Thus, TRPV1 plays an essential role in the response to external stimuli within the oral cavity, facilitating
the maintenance of tissue balance (Takahashi et al., 2020). Its activation releases neurotransmitters that
amplify nociceptive signals to the central nervous system, intensifying thermal sensation and algesia in
oral tissues (Arendt-Nielsen et al., 2022). Therefore, understanding TRPV1-mediated pain modulation
in oral diseases could lead to new therapeutic opportunities for managing such conditions.
Under this context, the present review article provides a global approach that includes studies on the
specific localization of TRPV1 in oral cavity structures, such as dental components, epithelial tissue,
cranial nerves, tongue, and salivary glands. Its link with painful conditions and its impact on
inflammatory and hyperesthetic processes, as well as the relationship between TRPV1 and conditions
such as cancer and COVID-19, are also addressed. Finally, the possible clinical and therapeutic
applications are discussed, highlighting their relevance in developing new strategies for managing oral
pain and inflammatory oral diseases.
METHODOLOGY
A bibliographic search of scientific information related to the expression of TRPV1 in the oral cavity
was carried out through the Scopus and Pubmed databases. The analysis revealed 680 documents using
the following search language: trpv1 AND (mouth OR cavity OR oral OR teeth OR buccal) AND
(treatment OR COVID-19 OR cancer).
physiological concentrations of Na+, Mg2+, and Ca2+ (Hellwig et al., 2004) due to a hydrophilic bridge
that allows proton conductance and cation permeation (Hellwig et al., 2004).
TRPV1 was initially identified in thinly myelinated and unmyelinated slow-conducting primary
somatosensory afferent neurons of the dorsal root ganglia of the spinal cord (Andresen, 2019). However,
subsequent research has shown that this receptor is widely distributed in other body cell types and
tissues. It is essential to address its role in regions sensitive to stimuli that affect the receptor, such as
the oral cavity. In this area, TRPV1 is in sensory afferent nerve fibers, such as Aδ and C fibers (Smutzer
& Devassy, 2016). Furthermore, it is widely distributed in oral epithelial cells, where it plays a key role
in the inflammatory response and the regulation of local homeostasis (Moayedi et al., 2022). It has even
been reported that in keratinocytes, TRPV1 contributes to sensory perception and the modulation of the
immune system (Smutzer & Devassy, 2016).
Thus, TRPV1 plays an essential role in the response to external stimuli within the oral cavity, facilitating
the maintenance of tissue balance (Takahashi et al., 2020). Its activation releases neurotransmitters that
amplify nociceptive signals to the central nervous system, intensifying thermal sensation and algesia in
oral tissues (Arendt-Nielsen et al., 2022). Therefore, understanding TRPV1-mediated pain modulation
in oral diseases could lead to new therapeutic opportunities for managing such conditions.
Under this context, the present review article provides a global approach that includes studies on the
specific localization of TRPV1 in oral cavity structures, such as dental components, epithelial tissue,
cranial nerves, tongue, and salivary glands. Its link with painful conditions and its impact on
inflammatory and hyperesthetic processes, as well as the relationship between TRPV1 and conditions
such as cancer and COVID-19, are also addressed. Finally, the possible clinical and therapeutic
applications are discussed, highlighting their relevance in developing new strategies for managing oral
pain and inflammatory oral diseases.
METHODOLOGY
A bibliographic search of scientific information related to the expression of TRPV1 in the oral cavity
was carried out through the Scopus and Pubmed databases. The analysis revealed 680 documents using
the following search language: trpv1 AND (mouth OR cavity OR oral OR teeth OR buccal) AND
(treatment OR COVID-19 OR cancer).
pág. 3541
Regarding the exclusion criteria, presentations, reports, and conference papers were eliminated. Articles
and reviews written in a language other than English were excluded, as were duplicate elements. From
the above, the number of manuscripts was reduced to 278.
Subsequently, a second filter was carried out based on the title, omitting information that was not directly
related to the topic of this review. Next, a third screen was applied based on the scope of the summaries
with the eventual evaluation of the total content of the articles considering the effectiveness of the
research presented in each of them. With this review, 27 articles were identified whose contributions
support the topic in question. 23 documents were also included to complement the general information
regarding TRPV1 and the oral cavity anatomy. The integration of these sources allows for a more
detailed discussion of its molecular functions, associated signaling pathways, and potential clinical
implications in oral health and disease.
RESULTS AND DISCUSSION
This is how the oral cavity is constructed.
The stomatognathic system is a morphofunctional unit made up of bone, muscular, nervous, and
glandular structures articulated at the craniofacial level (Zieliński et al., 2021) (Figure 1A). It can
integrate with the digestive, respiratory, and phonatory systems and participate in the sensory perception
of taste, touch, and balance (Gualdrón-Bobadilla et al., 2022).
Within this system is the oral cavity (Figure 1B), which is internally lined by the mucosa, composed of
stratified squamous epithelium and is kept hydrated thanks to the secretion of the submandibular and
sublingual salivary glands (McKnight et al., 2024). The oral cavity is primarily made up of the tongue.
It is delimited by the alveolar processes with teeth in the anterior and lateral region, while posteriorly, it
communicates with the oropharynx through the isthmus of the fauces (Xia, 2023). The roof constitutes
the hard palate in the anterior portion and the soft palate in the posterior portion, from which the uvula
extends. At the same time, the floor is formed by the mylohyoid muscles (Devine & Zur, 2021).
Regarding the exclusion criteria, presentations, reports, and conference papers were eliminated. Articles
and reviews written in a language other than English were excluded, as were duplicate elements. From
the above, the number of manuscripts was reduced to 278.
Subsequently, a second filter was carried out based on the title, omitting information that was not directly
related to the topic of this review. Next, a third screen was applied based on the scope of the summaries
with the eventual evaluation of the total content of the articles considering the effectiveness of the
research presented in each of them. With this review, 27 articles were identified whose contributions
support the topic in question. 23 documents were also included to complement the general information
regarding TRPV1 and the oral cavity anatomy. The integration of these sources allows for a more
detailed discussion of its molecular functions, associated signaling pathways, and potential clinical
implications in oral health and disease.
RESULTS AND DISCUSSION
This is how the oral cavity is constructed.
The stomatognathic system is a morphofunctional unit made up of bone, muscular, nervous, and
glandular structures articulated at the craniofacial level (Zieliński et al., 2021) (Figure 1A). It can
integrate with the digestive, respiratory, and phonatory systems and participate in the sensory perception
of taste, touch, and balance (Gualdrón-Bobadilla et al., 2022).
Within this system is the oral cavity (Figure 1B), which is internally lined by the mucosa, composed of
stratified squamous epithelium and is kept hydrated thanks to the secretion of the submandibular and
sublingual salivary glands (McKnight et al., 2024). The oral cavity is primarily made up of the tongue.
It is delimited by the alveolar processes with teeth in the anterior and lateral region, while posteriorly, it
communicates with the oropharynx through the isthmus of the fauces (Xia, 2023). The roof constitutes
the hard palate in the anterior portion and the soft palate in the posterior portion, from which the uvula
extends. At the same time, the floor is formed by the mylohyoid muscles (Devine & Zur, 2021).
pág. 3542
Figure 1. Anatomical representation of the stomatognathic system and the oral cavity. A) Lateral view
of the stomatognathic system, highlighting the segmentation into nasopharynx, oropharynx, and
hypopharynx. B) Detailed view of the oral cavity, showing its main structures. Also included are the
salivary glands, mylohyoid muscle, and the alveolar bone architecture associated with the dentition.
TRPV1: A key receptor in dental health
Teeth are key structures within the oral cavity, essential for chewing and digestion. Dental anatomy
(Figure 2A) comprises three main sections: the crown, the neck, and the root. Due to mineralization
processes, the crown has enamel, the outermost layer (Lacruz et al., 2017). This structure protects dentin,
a tissue structured by odontoblasts, with a yellow tone that is exposed when the enamel wears away
(Lacruz et al., 2017). According to Kamakura (2015), the dental neck connects the crown with the root,
located at the junction between the enamel and the cementum. The pulp is located inside the tooth and
is described as a vascularized tissue with nerve fibers extending to the root through the canal. Finally,
the root connects to the alveolar bone through the periodontal ligament, a tissue that contains nerves and
blood vessels.
Of these dental structures, TRPV1 expression has been identified in odontoblasts (Figure 2B),
suggesting its participation in sensory transduction (Okumura et al., 2005). In this context, the
"hydrodynamic receptor" theory stands out, which postulates the action of odontoblasts as
Figure 1. Anatomical representation of the stomatognathic system and the oral cavity. A) Lateral view
of the stomatognathic system, highlighting the segmentation into nasopharynx, oropharynx, and
hypopharynx. B) Detailed view of the oral cavity, showing its main structures. Also included are the
salivary glands, mylohyoid muscle, and the alveolar bone architecture associated with the dentition.
TRPV1: A key receptor in dental health
Teeth are key structures within the oral cavity, essential for chewing and digestion. Dental anatomy
(Figure 2A) comprises three main sections: the crown, the neck, and the root. Due to mineralization
processes, the crown has enamel, the outermost layer (Lacruz et al., 2017). This structure protects dentin,
a tissue structured by odontoblasts, with a yellow tone that is exposed when the enamel wears away
(Lacruz et al., 2017). According to Kamakura (2015), the dental neck connects the crown with the root,
located at the junction between the enamel and the cementum. The pulp is located inside the tooth and
is described as a vascularized tissue with nerve fibers extending to the root through the canal. Finally,
the root connects to the alveolar bone through the periodontal ligament, a tissue that contains nerves and
blood vessels.
Of these dental structures, TRPV1 expression has been identified in odontoblasts (Figure 2B),
suggesting its participation in sensory transduction (Okumura et al., 2005). In this context, the
"hydrodynamic receptor" theory stands out, which postulates the action of odontoblasts as
pág. 3543
mechanosensors capable of detecting changes in fluid pressure within the dentinal tubules, which
contributes to the perception of dental pain (Wen et al., 2017). When enamel is worn or damaged, dentin
exposure can intensify this response and promote the activation of TRPV1. After its stimulation,
inflammatory mediators, such as ATP, are released, which acts as a paracrine signal by binding to
purinergic P2X3 receptors (Hossain et al., 2019) (Figure 2B). P2X3 is predominantly located in Aδ
fibers (myelinated, responsible for acute and rapid pain) and C (unmyelinated, associated with dull and
persistent pain). It is crucial in transmitting nociceptive signals to the central nervous system (Hossain
et al., 2019). Thus, TRPV1 allows the integration of signals that influence dental hypersensitivity.
Regarding other regions, Sooampon et al. (2013) mention that TRPV1 is also located in human
periodontal ligament cells (Figure 2C), where its interaction by capsaicin modulates the homeostasis of
the osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL) axis. This
mechanism alludes to the regulation of bone resorption by TRPV1 based on the formation of osteoclasts.
Regarding thermal stimulation, the expression of TNF-α is induced through a calcium and protein kinase
C (PKC)-dependent pathway in a process that requires reorganization of the cytoskeleton. Osada et al.
(2022) identified that TRPV1 and acid-sensitive ion channels are stimulated in response to acidification
of the periodontium caused by tooth movement. The above contributes to mechanical hypersensitivity
by stimulating inflammatory signaling pathways, such as that mediated by protease-activated receptor
2 (PAR2). Therefore, TRPV1 sensitization could intensify pain perception during orthodontic treatment.
Gibbs et al. (2012) determined that in the dental pulp, the expression of TRPV1 is relatively low.
However, its regulation by inflammatory mediators can increase thermal sensitivity and enhance
nociceptive transmission (Figure 2D). The above favors the development of hyperalgesia in pathological
states such as irreversible pulpitis, where inflammation and hyperemia sensitize nociceptive fibers,
which is exacerbated by the release of neuropeptides that amplify the algesic signal. On the other hand,
TRVP1 is found to a limited extent in neurons that innervate the pulp compared to those of the
periodontal ligament, which suggests a difference in the ability to detect stimuli between both tissues.
This distribution could influence the variability of odontogenic pain perception.
mechanosensors capable of detecting changes in fluid pressure within the dentinal tubules, which
contributes to the perception of dental pain (Wen et al., 2017). When enamel is worn or damaged, dentin
exposure can intensify this response and promote the activation of TRPV1. After its stimulation,
inflammatory mediators, such as ATP, are released, which acts as a paracrine signal by binding to
purinergic P2X3 receptors (Hossain et al., 2019) (Figure 2B). P2X3 is predominantly located in Aδ
fibers (myelinated, responsible for acute and rapid pain) and C (unmyelinated, associated with dull and
persistent pain). It is crucial in transmitting nociceptive signals to the central nervous system (Hossain
et al., 2019). Thus, TRPV1 allows the integration of signals that influence dental hypersensitivity.
Regarding other regions, Sooampon et al. (2013) mention that TRPV1 is also located in human
periodontal ligament cells (Figure 2C), where its interaction by capsaicin modulates the homeostasis of
the osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL) axis. This
mechanism alludes to the regulation of bone resorption by TRPV1 based on the formation of osteoclasts.
Regarding thermal stimulation, the expression of TNF-α is induced through a calcium and protein kinase
C (PKC)-dependent pathway in a process that requires reorganization of the cytoskeleton. Osada et al.
(2022) identified that TRPV1 and acid-sensitive ion channels are stimulated in response to acidification
of the periodontium caused by tooth movement. The above contributes to mechanical hypersensitivity
by stimulating inflammatory signaling pathways, such as that mediated by protease-activated receptor
2 (PAR2). Therefore, TRPV1 sensitization could intensify pain perception during orthodontic treatment.
Gibbs et al. (2012) determined that in the dental pulp, the expression of TRPV1 is relatively low.
However, its regulation by inflammatory mediators can increase thermal sensitivity and enhance
nociceptive transmission (Figure 2D). The above favors the development of hyperalgesia in pathological
states such as irreversible pulpitis, where inflammation and hyperemia sensitize nociceptive fibers,
which is exacerbated by the release of neuropeptides that amplify the algesic signal. On the other hand,
TRVP1 is found to a limited extent in neurons that innervate the pulp compared to those of the
periodontal ligament, which suggests a difference in the ability to detect stimuli between both tissues.
This distribution could influence the variability of odontogenic pain perception.
pág. 3544
Figure 2. TRPV1 expression in dental tissues and its involvement in sensory transduction and pain
perception. (A) Anatomy of the tooth, composed of crown, neck, and root. The enamel, dentin, pulp,
and periodontal ligament stand out. (B) In odontoblasts, TRPV1 mediates the release of inflammatory
mediators in response to thermal and mechanical stimuli, activating purinergic receptors (P2X3) in Aδ
and C fibers. (C) TRPV1 regulates bone resorption in the periodontal ligament and participates in
mechanical hypersensitivity through PAR2-dependent inflammatory pathways. (D) In the dental pulp,
its expression is low under normal conditions but increases in the presence of inflammation, favoring
hyperalgesia in pathologies such as irreversible pulpitis.
TRPV1 is a bridge between sensation, inflammation, and immunity in the oral cavity
TRPV1 expression in the oral cavity encompasses various epithelial tissues and neuroanatomical
structures (Takahashi et al., 2020). Moayedi et al. (2022) highlight its location in intraepidermal nerve
fibers and the terminal bulbs of Krause (Figure 3). In these areas, TRPV1 facilitates stimulus detection
and is involved in ionic balance and modulation of epithelial permeability. Also, it triggers the release
of proinflammatory neuropeptides (substance P and calcitonin gene-related peptide), essential for
maintaining the oral microenvironment. Also, its role in neuronal plasticity alludes to a contribution to
physiological adaptation through sensitization and desensitization of primary afferent fibers.
Consequently, a modulated response to thermal fluctuations and exposure to pathogens is generated
(Takahashi et al., 2020). In this way, neuronal plasticity can influence orofacial pain perception,
protective reflexes, and mucosal homeostasis. Even according to the information collected by Takahashi
Figure 2. TRPV1 expression in dental tissues and its involvement in sensory transduction and pain
perception. (A) Anatomy of the tooth, composed of crown, neck, and root. The enamel, dentin, pulp,
and periodontal ligament stand out. (B) In odontoblasts, TRPV1 mediates the release of inflammatory
mediators in response to thermal and mechanical stimuli, activating purinergic receptors (P2X3) in Aδ
and C fibers. (C) TRPV1 regulates bone resorption in the periodontal ligament and participates in
mechanical hypersensitivity through PAR2-dependent inflammatory pathways. (D) In the dental pulp,
its expression is low under normal conditions but increases in the presence of inflammation, favoring
hyperalgesia in pathologies such as irreversible pulpitis.
TRPV1 is a bridge between sensation, inflammation, and immunity in the oral cavity
TRPV1 expression in the oral cavity encompasses various epithelial tissues and neuroanatomical
structures (Takahashi et al., 2020). Moayedi et al. (2022) highlight its location in intraepidermal nerve
fibers and the terminal bulbs of Krause (Figure 3). In these areas, TRPV1 facilitates stimulus detection
and is involved in ionic balance and modulation of epithelial permeability. Also, it triggers the release
of proinflammatory neuropeptides (substance P and calcitonin gene-related peptide), essential for
maintaining the oral microenvironment. Also, its role in neuronal plasticity alludes to a contribution to
physiological adaptation through sensitization and desensitization of primary afferent fibers.
Consequently, a modulated response to thermal fluctuations and exposure to pathogens is generated
(Takahashi et al., 2020). In this way, neuronal plasticity can influence orofacial pain perception,
protective reflexes, and mucosal homeostasis. Even according to the information collected by Takahashi
pág. 3545
et al. (2020), in gingival tissue, TRPV1 exerts a protective function of the epithelial barrier. It has also
been linked to the progression of periodontal diseases, including gingivitis and periodontitis. This is
because TRPV1 promotes the activation of macrophages and dendritic cells, favoring the release of
proinflammatory cytokines such as IL-1β, TNF-α, and IL-6.
Figure 3. TRPV1 in intraepidermal nerve fibers, terminal bulbs of Krause, and gingival tissue. TRPV1
induces the release of proinflammatory neuropeptides, promoting inflammation and periodontal
pathologies through immune activation and the release of proinflammatory cytokines.
Nerve bundles with TRPV1 are abundantly distributed in the lamina propria of circumvallate, foliate,
and fungiform papillae, with branches penetrating the taste buds (Kido et al., 2017). Although TRPV1
immunoreactivity within taste cells is limited, it is strongly expressed in the surrounding epithelium,
promoting peripheral sensory uptake (Kido et al., 2017). In fact, according to Roper (2014), TRPV1
favors the detection of thermal and chemical stimuli on the tongue by modulating the response to
pungent compounds such as capsaicin. This effect is achieved by associating the tissue with the afferent
fibers of the trigeminal nerve with the consequent transmission of nociceptive signals to the central
nervous system. Its sensory role is enhanced by interaction with TRPA1 receptors from a synergistic
response to irritants. Furthermore, the strong expression of TRPV1 at the top of the palatal wrinkles,
structures that protrude into the oral cavity, suggests the receptor's involvement in guiding food to the
larynx (Kido et al., 2017). Subsequently, in the afferent fibers of the trigeminal nerve, TRPV1 triggers
et al. (2020), in gingival tissue, TRPV1 exerts a protective function of the epithelial barrier. It has also
been linked to the progression of periodontal diseases, including gingivitis and periodontitis. This is
because TRPV1 promotes the activation of macrophages and dendritic cells, favoring the release of
proinflammatory cytokines such as IL-1β, TNF-α, and IL-6.
Figure 3. TRPV1 in intraepidermal nerve fibers, terminal bulbs of Krause, and gingival tissue. TRPV1
induces the release of proinflammatory neuropeptides, promoting inflammation and periodontal
pathologies through immune activation and the release of proinflammatory cytokines.
Nerve bundles with TRPV1 are abundantly distributed in the lamina propria of circumvallate, foliate,
and fungiform papillae, with branches penetrating the taste buds (Kido et al., 2017). Although TRPV1
immunoreactivity within taste cells is limited, it is strongly expressed in the surrounding epithelium,
promoting peripheral sensory uptake (Kido et al., 2017). In fact, according to Roper (2014), TRPV1
favors the detection of thermal and chemical stimuli on the tongue by modulating the response to
pungent compounds such as capsaicin. This effect is achieved by associating the tissue with the afferent
fibers of the trigeminal nerve with the consequent transmission of nociceptive signals to the central
nervous system. Its sensory role is enhanced by interaction with TRPA1 receptors from a synergistic
response to irritants. Furthermore, the strong expression of TRPV1 at the top of the palatal wrinkles,
structures that protrude into the oral cavity, suggests the receptor's involvement in guiding food to the
larynx (Kido et al., 2017). Subsequently, in the afferent fibers of the trigeminal nerve, TRPV1 triggers
pág. 3546
central and peripheral sensitization (Saunders et al., 2013). This mechanism favors orofacial
hyperalgesia and the development of chronic pain in conditions such as trigeminal neuralgia and
temporomandibular dysfunction (Roper, 2014). Thus, cooperation with sensory proteins (TRPA1 and
acid-sensitive ion channels) in these nerves increases the nociceptive response and synaptic plasticity in
trigeminal neuronal networks (Saunders et al., 2013).
Regarding its presence in salivary glands, TRPV1 regulates the function of ion channels and aquaporin
transporters (Takahashi et al., 2020). However, its involvement in salivary secretion does not seem to
be direct through the transcellular pathway (Choi et al., 2014). It has been observed that high
concentrations of capsaicin (100 μM) reduce transepithelial resistance, inducing a possible effect on
paracellular permeability (Choi et al., 2014). Likewise, it plays a relevant role in the innate immune
response, acting as a mediator in the detection of oral pathogens and in triggering pro-inflammatory
pathways (Tynan et al., 2019). Its intervention in tissue remodeling makes it a determining factor in the
healing of epithelial wounds, ensuring oral tissue's structural and functional restoration after mechanical
or infectious aggression (Takahashi et al., 2014).
The duality of TRPV1 in oral cancer: cytotoxicity or tumor resistance
Marincsák et al. (2009) documented the overexpression of TRPV1 in oral squamous cell carcinoma
(OSCC) through the significant increase in mRNA and protein levels compared to healthy epithelial
tissue. At the molecular level, the interaction of TRPV1 by agonists unleashed a massive influx of
intracellular Ca²⁺, recruiting effector caspases and the release of cytochrome c from mitochondria,
promoting apoptosis in tumor cells (Zhai et al., 2020) (Figure 4A). Nevertheless, TRPV1-induced
cytotoxicity is highly dependent on the agonist concentration and tumor context since sustained
activation of the channel can unleash survival mechanisms mediated by the PI3K/Akt pathway (Figure
4B), inducing cell proliferation and resistance to apoptosis (Zhai et al., 2020).
Hypersensitization of TRPV1 in oral cancer is associated with an increase in mechanical and chemical
pain, correlating with the increased expression of TRPV1 in trigeminal ganglion neurons that innervate
the tumor (Sawicki et al., 2022). The opening of TRPV1 in the tumor microenvironment is controlled
by the PAR2 receptor (Figure 4B), leading to sensitization of the channel through phosphorylation by
protein kinases A and C (PKA and PKC) (Scheff et al., 2022). In preclinical models, PAR2 inhibition
central and peripheral sensitization (Saunders et al., 2013). This mechanism favors orofacial
hyperalgesia and the development of chronic pain in conditions such as trigeminal neuralgia and
temporomandibular dysfunction (Roper, 2014). Thus, cooperation with sensory proteins (TRPA1 and
acid-sensitive ion channels) in these nerves increases the nociceptive response and synaptic plasticity in
trigeminal neuronal networks (Saunders et al., 2013).
Regarding its presence in salivary glands, TRPV1 regulates the function of ion channels and aquaporin
transporters (Takahashi et al., 2020). However, its involvement in salivary secretion does not seem to
be direct through the transcellular pathway (Choi et al., 2014). It has been observed that high
concentrations of capsaicin (100 μM) reduce transepithelial resistance, inducing a possible effect on
paracellular permeability (Choi et al., 2014). Likewise, it plays a relevant role in the innate immune
response, acting as a mediator in the detection of oral pathogens and in triggering pro-inflammatory
pathways (Tynan et al., 2019). Its intervention in tissue remodeling makes it a determining factor in the
healing of epithelial wounds, ensuring oral tissue's structural and functional restoration after mechanical
or infectious aggression (Takahashi et al., 2014).
The duality of TRPV1 in oral cancer: cytotoxicity or tumor resistance
Marincsák et al. (2009) documented the overexpression of TRPV1 in oral squamous cell carcinoma
(OSCC) through the significant increase in mRNA and protein levels compared to healthy epithelial
tissue. At the molecular level, the interaction of TRPV1 by agonists unleashed a massive influx of
intracellular Ca²⁺, recruiting effector caspases and the release of cytochrome c from mitochondria,
promoting apoptosis in tumor cells (Zhai et al., 2020) (Figure 4A). Nevertheless, TRPV1-induced
cytotoxicity is highly dependent on the agonist concentration and tumor context since sustained
activation of the channel can unleash survival mechanisms mediated by the PI3K/Akt pathway (Figure
4B), inducing cell proliferation and resistance to apoptosis (Zhai et al., 2020).
Hypersensitization of TRPV1 in oral cancer is associated with an increase in mechanical and chemical
pain, correlating with the increased expression of TRPV1 in trigeminal ganglion neurons that innervate
the tumor (Sawicki et al., 2022). The opening of TRPV1 in the tumor microenvironment is controlled
by the PAR2 receptor (Figure 4B), leading to sensitization of the channel through phosphorylation by
protein kinases A and C (PKA and PKC) (Scheff et al., 2022). In preclinical models, PAR2 inhibition
pág. 3547
has been shown to reduce capsaicin aversion in behavioral assays, suggesting a functional interaction
between these receptors in the perception of OSCC-induced pain (Scheff et al., 2022).
Figure 4. Expression and function of TRPV1 in oral squamous cell carcinoma (OSCC). (A) Activation
of TRPV1 by agonists increases intracellular Ca²⁺, promoting mitochondrial depolarization, production
of reactive oxygen species, and apoptosis. (B) In contrast, TRPV1 can generate survival pathways
mediated by PI3K/Akt in a specific tumor context, favoring cell proliferation. PAR2 receptor regulates
TRPV1 sensitization through phosphorylation by protein kinases, influencing tumor progression and
pain perception in OSCC. Phospholipase C (PLC), Inositol 1,4,5-trisphosphate (IP3), Store-Operated
Calcium Channels (SOC), Ca2+-Sarcoplasmic/Endoplasmic Reticulum ATPase (SERCA),
Phosphatidylinositol 3-kinase (PI3K), Phosphoinositide-dependent Kinase 1 & 2 (PDK1 & 2), Proto-
oncogene Tyrosine-protein Kinase Src (SRC), Protein Kinase B (AKT). Created in
TRPV1 has been proposed as a diagnostic biomarker due to its early overexpression in precancerous
lesions and in the epithelium surrounding the tumor (Marincsák et al., 2009). As a treatment,
intratumoral administration of capsazepine can reduce tumor size without affecting healthy tissues,
suggesting that TRPV1 antagonists could effectively inhibit the neoplastic progression of OSCC
(Gonzales et al., 2014). As a perspective, TRPV1 modulation could offer a targeted analgesic approach
to patients with OSCC, minimizing chemical hypersensitivity without compromising normal sensory
function (Sawicki et al., 2022).
has been shown to reduce capsaicin aversion in behavioral assays, suggesting a functional interaction
between these receptors in the perception of OSCC-induced pain (Scheff et al., 2022).
Figure 4. Expression and function of TRPV1 in oral squamous cell carcinoma (OSCC). (A) Activation
of TRPV1 by agonists increases intracellular Ca²⁺, promoting mitochondrial depolarization, production
of reactive oxygen species, and apoptosis. (B) In contrast, TRPV1 can generate survival pathways
mediated by PI3K/Akt in a specific tumor context, favoring cell proliferation. PAR2 receptor regulates
TRPV1 sensitization through phosphorylation by protein kinases, influencing tumor progression and
pain perception in OSCC. Phospholipase C (PLC), Inositol 1,4,5-trisphosphate (IP3), Store-Operated
Calcium Channels (SOC), Ca2+-Sarcoplasmic/Endoplasmic Reticulum ATPase (SERCA),
Phosphatidylinositol 3-kinase (PI3K), Phosphoinositide-dependent Kinase 1 & 2 (PDK1 & 2), Proto-
oncogene Tyrosine-protein Kinase Src (SRC), Protein Kinase B (AKT). Created in
TRPV1 has been proposed as a diagnostic biomarker due to its early overexpression in precancerous
lesions and in the epithelium surrounding the tumor (Marincsák et al., 2009). As a treatment,
intratumoral administration of capsazepine can reduce tumor size without affecting healthy tissues,
suggesting that TRPV1 antagonists could effectively inhibit the neoplastic progression of OSCC
(Gonzales et al., 2014). As a perspective, TRPV1 modulation could offer a targeted analgesic approach
to patients with OSCC, minimizing chemical hypersensitivity without compromising normal sensory
function (Sawicki et al., 2022).
pág. 3548
Oral neuroinflammation due to COVID-19 and the role of TRPV1
SARS-CoV-2 infection has been related to various sensory alterations, including oral hypersensitivity
and loss of taste, sparking interest in its molecular mechanisms (Nanjo et al., 2019). Since TRPV1 is
presented in sensory neurons in this area, a probable connection is established between the dysfunction
of these receptors and the alterations observed in patients with COVID-19 (Maaroufi, 2021).
The S protein of SARS-CoV-2 can interact with TRPV1 through ankyrin repeat binding motifs
(Maaroufi, 2021). The above could alter the functionality of TRPV1, affecting the transmission of
sensory signals in the oral cavity and contributing to the dysgeusia observed in infected patients
(Tsuchiya, 2023). Furthermore, since TRPV1 is involved in the inflammatory response, facilitating the
release of IL-6 and TNF-α, it exacerbates inflammatory processes and generates oral hypersensitivity
(Takahashi et al., 2020). Other studies have shown that respiratory viruses such as respiratory syncytial
virus and measles can induce the overexpression of TRPV1 in epithelial cells and neurons, evoking a
similar mechanism in SARS-CoV-2 infection (Omar et al., 2017).
As mentioned above, modifications in TRPV1 in the oral mucosa are linked to the immune response.
TRPV1 activation has been shown to play a crucial role in generating adaptive immune responses,
suggesting that its dysfunction affects the effectiveness of the response against the virus (Tynan et al.,
2019). In this sense, the possibility of using TRPV1 agonists as adjuvants in vaccines against SARS-
CoV-2 is raised (Maaroufi, 2021). Since TRPV1 is associated with the regulation of lung inflammation,
it could be related to the multisystem symptomatology of COVID-19, including effects at the
cardiovascular and neuronal level (Omar et al., 2017; Liviero et al., 2021; Tsuchiya, 2023). These
findings highlight the relevance of TRPV1 in the oral pathophysiology of COVID-19 infection and raise
new therapeutic perspectives to mitigate its effects in the oral cavity.
Therapeutic perspectives on TRPV1 in the treatment of oral disorders
The TRPV1 receptor has emerged as a promising therapeutic target in managing orofacial pain and oral
inflammation. Its activation by agonists such as capsaicin and resiniferatoxin induces progressive
neuronal desensitization, reducing nociceptive excitability and modulating neurogenic inflammation
(Smutzer & Devassy, 2016). The application of capsaicin has been shown to modulate the release of
pro-inflammatory neuropeptides, allowing the management of neuropathic pain associated with
Oral neuroinflammation due to COVID-19 and the role of TRPV1
SARS-CoV-2 infection has been related to various sensory alterations, including oral hypersensitivity
and loss of taste, sparking interest in its molecular mechanisms (Nanjo et al., 2019). Since TRPV1 is
presented in sensory neurons in this area, a probable connection is established between the dysfunction
of these receptors and the alterations observed in patients with COVID-19 (Maaroufi, 2021).
The S protein of SARS-CoV-2 can interact with TRPV1 through ankyrin repeat binding motifs
(Maaroufi, 2021). The above could alter the functionality of TRPV1, affecting the transmission of
sensory signals in the oral cavity and contributing to the dysgeusia observed in infected patients
(Tsuchiya, 2023). Furthermore, since TRPV1 is involved in the inflammatory response, facilitating the
release of IL-6 and TNF-α, it exacerbates inflammatory processes and generates oral hypersensitivity
(Takahashi et al., 2020). Other studies have shown that respiratory viruses such as respiratory syncytial
virus and measles can induce the overexpression of TRPV1 in epithelial cells and neurons, evoking a
similar mechanism in SARS-CoV-2 infection (Omar et al., 2017).
As mentioned above, modifications in TRPV1 in the oral mucosa are linked to the immune response.
TRPV1 activation has been shown to play a crucial role in generating adaptive immune responses,
suggesting that its dysfunction affects the effectiveness of the response against the virus (Tynan et al.,
2019). In this sense, the possibility of using TRPV1 agonists as adjuvants in vaccines against SARS-
CoV-2 is raised (Maaroufi, 2021). Since TRPV1 is associated with the regulation of lung inflammation,
it could be related to the multisystem symptomatology of COVID-19, including effects at the
cardiovascular and neuronal level (Omar et al., 2017; Liviero et al., 2021; Tsuchiya, 2023). These
findings highlight the relevance of TRPV1 in the oral pathophysiology of COVID-19 infection and raise
new therapeutic perspectives to mitigate its effects in the oral cavity.
Therapeutic perspectives on TRPV1 in the treatment of oral disorders
The TRPV1 receptor has emerged as a promising therapeutic target in managing orofacial pain and oral
inflammation. Its activation by agonists such as capsaicin and resiniferatoxin induces progressive
neuronal desensitization, reducing nociceptive excitability and modulating neurogenic inflammation
(Smutzer & Devassy, 2016). The application of capsaicin has been shown to modulate the release of
pro-inflammatory neuropeptides, allowing the management of neuropathic pain associated with
pág. 3549
peripheral hypersensitization (Chen et al., 2024). Likewise, resiniferatoxin, with greater potency and
lower systemic toxicity than capsaicin, has shown potential in the selective ablation of nociceptive fibers
without compromising general neuronal function (Smutzer & Devassy, 2016).
On the other hand, TRPV1 antagonists have gained relevance in developing anti-inflammatory and
analgesic treatments, particularly in managing hyperalgesia in patients with oral lesions. In the context
of periodontal pathology, the inhibition of TRPV1 by capsazepine has shown positive effects in
regulating bone resorption (Sooampon et al., 2013). However, its clinical application requires further
refinement, given that some antagonists have shown adverse effects on the regulation of intracellular
calcium (Smutzer & Devassy, 2016). This is due to the broad expression of TRPV1 in the nervous
system and other peripheral tissues (Smutzer & Devassy, 2016).
TRPV1 activation and blockade have been investigated as strategies to influence immune responses in
infectious and inflammatory diseases. This process enhances T cell and macrophage responses through
neuropeptide release in peripheral nociceptors (Tynan et al., 2024). This suggests its possible usefulness
in optimizing local immune responses, including those directed against oral pathogens. On the contrary,
the inhibition of TRPV1 can modulate inflammatory responses in oral tissues, having therapeutic
potential in periodontal diseases and pathological processes of the oral mucosa (Sooampon et al., 2013).
The study of TRPV1 as a therapeutic target offers an alternative route for treating oral conditions in
patients with pharmacological restrictions. Nevertheless, TRPV1 modulation may have dual effects
depending on the pathological context (Chen et al., 2024). That is why developing therapeutic strategies
based on this receptor requires a deeper understanding of its effects on immune balance and
inflammation. Designing drugs specific for TRPV1 in the oral cavity could represent a significant
innovation in regenerative dentistry and pain medicine.
CONCLUSIONS
The TRPV1 receptor plays a key role in the oral cavity by participating in sensory transduction,
inflammation, and tissue homeostasis. Its expression in various structures, such as dental components,
oral mucosa, cranial nerves, and salivary glands, highlights its importance in pain perception, immune
response, and modulation of pathophysiological processes. This receptor is associated with oral
squamous cell carcinoma's progression and sensory alterations in viral infections such as COVID-19.
peripheral hypersensitization (Chen et al., 2024). Likewise, resiniferatoxin, with greater potency and
lower systemic toxicity than capsaicin, has shown potential in the selective ablation of nociceptive fibers
without compromising general neuronal function (Smutzer & Devassy, 2016).
On the other hand, TRPV1 antagonists have gained relevance in developing anti-inflammatory and
analgesic treatments, particularly in managing hyperalgesia in patients with oral lesions. In the context
of periodontal pathology, the inhibition of TRPV1 by capsazepine has shown positive effects in
regulating bone resorption (Sooampon et al., 2013). However, its clinical application requires further
refinement, given that some antagonists have shown adverse effects on the regulation of intracellular
calcium (Smutzer & Devassy, 2016). This is due to the broad expression of TRPV1 in the nervous
system and other peripheral tissues (Smutzer & Devassy, 2016).
TRPV1 activation and blockade have been investigated as strategies to influence immune responses in
infectious and inflammatory diseases. This process enhances T cell and macrophage responses through
neuropeptide release in peripheral nociceptors (Tynan et al., 2024). This suggests its possible usefulness
in optimizing local immune responses, including those directed against oral pathogens. On the contrary,
the inhibition of TRPV1 can modulate inflammatory responses in oral tissues, having therapeutic
potential in periodontal diseases and pathological processes of the oral mucosa (Sooampon et al., 2013).
The study of TRPV1 as a therapeutic target offers an alternative route for treating oral conditions in
patients with pharmacological restrictions. Nevertheless, TRPV1 modulation may have dual effects
depending on the pathological context (Chen et al., 2024). That is why developing therapeutic strategies
based on this receptor requires a deeper understanding of its effects on immune balance and
inflammation. Designing drugs specific for TRPV1 in the oral cavity could represent a significant
innovation in regenerative dentistry and pain medicine.
CONCLUSIONS
The TRPV1 receptor plays a key role in the oral cavity by participating in sensory transduction,
inflammation, and tissue homeostasis. Its expression in various structures, such as dental components,
oral mucosa, cranial nerves, and salivary glands, highlights its importance in pain perception, immune
response, and modulation of pathophysiological processes. This receptor is associated with oral
squamous cell carcinoma's progression and sensory alterations in viral infections such as COVID-19.
pág. 3550
This evidence positions TRPV1 as a potential therapeutic target in stomatology, with applications in the
design of strategies for managing inflammatory diseases in the oral cavity.
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Devine, C., & Zur, K. (2021). Upper Airway Anatomy and Physiology. Diagnostic and
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Elokely, K., Velisetty, P., Delemotte, L., Palovcak, E., Klein, M. L., Rohacs, T., & Carnevale, V.
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resiniferatoxin. Proceedings of the National Academy of Sciences, 113(2), E137-E145.
Gibbs, J. L., Melnyk, J. L., & Basbaum, A. (2011). Differential TRPV1 and TRPV2 channel
expression in dental pulp. Journal of dental research, 90(6), 765-770.
Gonzales, C. B., Kirma, N. B., Jorge, J., Chen, R., Henry, M. A., Luo, S., & Hargreaves, K. M.
(2014). Vanilloids induce oral cancer apoptosis independent of TRPV1. Oral oncology, 50(5), 437–447.
This evidence positions TRPV1 as a potential therapeutic target in stomatology, with applications in the
design of strategies for managing inflammatory diseases in the oral cavity.
REFERENCES
Andrei, C., Zanfirescu, A., Nițulescu, G. M., Olaru, O. T., & Negreș, S. (2023). Natural active
ingredients and TRPV1 modulation: focus on key chemical moieties involved in ligand-target
interaction. Plants, 12(2), 339.
Andresen, M. C. (2019). Understanding diverse TRPV1 signaling–an update. F1000Research,
8.
Arendt-Nielsen, L., Carstens, E., Proctor, G., Boucher, Y., Clavé, P., Albin Nielsen, K., ... &
Reeh, P. W. (2022). The role of TRP Channels in Nicotinic provoked Pain and Irritation from the oral
cavity and Throat: translating Animal Data to humans. Nicotine and Tobacco Research, 24(12), 1849-
1860.
Chen, J., Sun, W., Zhu, Y., Zhao, F., Deng, S., Tian, M., ... & Gong, Y. (2024). TRPV1: The key
bridge in neuroimmune interactions. Journal of Intensive Medicine.
Choi, S., Shin, Y. H., Namkoong, E., Hwang, S. M., Cong, X., Yu, G., & Park, K. (2014). TRPV1
in salivary gland epithelial cells is not involved in salivary secretion via transcellular pathway. The
Korean Journal of Physiology & Pharmacology: Official Journal of the Korean Physiological Society
and the Korean Society of Pharmacology, 18(6), 525.
Devine, C., & Zur, K. (2021). Upper Airway Anatomy and Physiology. Diagnostic and
Interventional Bronchoscopy in Children, 17-37.
Elokely, K., Velisetty, P., Delemotte, L., Palovcak, E., Klein, M. L., Rohacs, T., & Carnevale, V.
(2016). Understanding TRPV1 activation by ligands: Insights from the binding modes of capsaicin and
resiniferatoxin. Proceedings of the National Academy of Sciences, 113(2), E137-E145.
Gibbs, J. L., Melnyk, J. L., & Basbaum, A. (2011). Differential TRPV1 and TRPV2 channel
expression in dental pulp. Journal of dental research, 90(6), 765-770.
Gonzales, C. B., Kirma, N. B., Jorge, J., Chen, R., Henry, M. A., Luo, S., & Hargreaves, K. M.
(2014). Vanilloids induce oral cancer apoptosis independent of TRPV1. Oral oncology, 50(5), 437–447.
pág. 3551
Gualdrón-Bobadilla, G. F., Briceño-Martínez, A. P., Caicedo-Téllez, V., Pérez-Reyes, G., Silva-
Paredes, C., Ortiz-Benavides, R., ... & Bermúdez, V. (2022). Stomatognathic system changes in obese
patients undergoing bariatric surgery: a systematic review—Journal of Personalized Medicine, 12(10),
1541.
Hellwig, N., Plant, T. D., Janson, W., Schäfer, M., Schultz, G., & Schaefer, M. (2004). TRPV1
acts as proton channel to induce acidification in nociceptive neurons. Journal of Biological
Chemistry, 279(33), 34553-34561.
Huang, Y., Fliegert, R., Guse, A. H., Lü, W., & Du, J. (2020). A structural overview of the ion
channels of the TRPM family. Cell Calcium, 85, 102111.
Hossain, M. Z., Bakri, M. M., Yahya, F., Ando, H., Unno, S., & Kitagawa, J. (2019). The role
of transient receptor potential (TRP) channels in the transduction of dental pain. International journal
of molecular sciences, 20(3), 526.
Kamakura, S. (2015). Tooth and tooth-supporting structures. Advances in Metallic
Biomaterials: Tissues, Materials and Biological Reactions, 99–122.
Kido, M. A., Yoshimoto, R. U., Aijima, R., Cao, A. L., & Gao, W. Q. (2017). The oral mucosal
membrane and transient receptor potential channels. Journal of Oral Science, 59(2), 189-193.
Liao, M., Cao, E., Julius, D., & Cheng, Y. (2013). Structure of the TRPV1 ion channel
determined by electron cryo-microscopy. Nature, 504(7478), 107–112.
Liu, M., Jia, X., Liu, H., He, R., Zhang, X., & Shao, Y. (2022). Role of TRPV1 in respiratory
disease and association with traditional Chinese medicine: A literature review. Biomedicine &
Pharmacotherapy, 155, 113676.
Liviero, F., Campisi, M., Mason, P., & Pavanello, S. (2021). Transient receptor potential
vanilloid subtype 1: potential role in infection, susceptibility, symptoms and treatment of COVID-19.
Frontiers in Medicine, 8, 753819.
Lacruz, R. S., Habelitz, S., Wright, J. T., & Paine, M. L. (2017). Dental enamel formation and
implications for oral health and disease. Physiological reviews, 97(3), 939–993.
Gualdrón-Bobadilla, G. F., Briceño-Martínez, A. P., Caicedo-Téllez, V., Pérez-Reyes, G., Silva-
Paredes, C., Ortiz-Benavides, R., ... & Bermúdez, V. (2022). Stomatognathic system changes in obese
patients undergoing bariatric surgery: a systematic review—Journal of Personalized Medicine, 12(10),
1541.
Hellwig, N., Plant, T. D., Janson, W., Schäfer, M., Schultz, G., & Schaefer, M. (2004). TRPV1
acts as proton channel to induce acidification in nociceptive neurons. Journal of Biological
Chemistry, 279(33), 34553-34561.
Huang, Y., Fliegert, R., Guse, A. H., Lü, W., & Du, J. (2020). A structural overview of the ion
channels of the TRPM family. Cell Calcium, 85, 102111.
Hossain, M. Z., Bakri, M. M., Yahya, F., Ando, H., Unno, S., & Kitagawa, J. (2019). The role
of transient receptor potential (TRP) channels in the transduction of dental pain. International journal
of molecular sciences, 20(3), 526.
Kamakura, S. (2015). Tooth and tooth-supporting structures. Advances in Metallic
Biomaterials: Tissues, Materials and Biological Reactions, 99–122.
Kido, M. A., Yoshimoto, R. U., Aijima, R., Cao, A. L., & Gao, W. Q. (2017). The oral mucosal
membrane and transient receptor potential channels. Journal of Oral Science, 59(2), 189-193.
Liao, M., Cao, E., Julius, D., & Cheng, Y. (2013). Structure of the TRPV1 ion channel
determined by electron cryo-microscopy. Nature, 504(7478), 107–112.
Liu, M., Jia, X., Liu, H., He, R., Zhang, X., & Shao, Y. (2022). Role of TRPV1 in respiratory
disease and association with traditional Chinese medicine: A literature review. Biomedicine &
Pharmacotherapy, 155, 113676.
Liviero, F., Campisi, M., Mason, P., & Pavanello, S. (2021). Transient receptor potential
vanilloid subtype 1: potential role in infection, susceptibility, symptoms and treatment of COVID-19.
Frontiers in Medicine, 8, 753819.
Lacruz, R. S., Habelitz, S., Wright, J. T., & Paine, M. L. (2017). Dental enamel formation and
implications for oral health and disease. Physiological reviews, 97(3), 939–993.
pág. 3552
Maaroufi, H. (2021). Interactions of SARS-CoV-2 spike protein and transient receptor potential
(TRP) cation channels could explain smell, taste, and/or chemesthesis disorders—arXiv preprint
arXiv:2101.06294.
Marincsák, R., Tóth, B. I., Czifra, G., Márton, I., Rédl, P., Tar, I., ... & Bíró, T. (2009). Increased
expression of TRPV1 in squamous cell carcinoma of the human tongue. Oral diseases, 15(5), 328-335.
McKnight, C. A., Diehl, L. J., & Bergin, I. L. (2024). Digestive Tract and Salivary Glands.
In Haschek and Rousseaux's Handbook of Toxicologic Pathology (pp. 1-148). Academic Press.
Moayedi, Y., Michlig, S., Park, M., Koch, A., & Lumpkin, E. A. (2022). Localization of TRP
channels in healthy oral mucosa from human donors. eneuro, 9(6).
Nadezhdin, K. D., Neuberger, A., Nikolaev, Y. A., Murphy, L. A., Gracheva, E. O., Bagriantsev,
S. N., & Sobolevsky, A. I. (2021). Extracellular cap domain is an essential component of the TRPV1
gating mechanism. Nature communications, 12(1), 2154.
Nanjo, Y., Okuma, T., Kuroda, Y., Hayakawa, E., Shibayama, K., Akimoto, T., ... & Takahashi,
K. (2022). Multiple Types of Taste Disorders among Patients with COVID-19. Internal Medicine,
61(14), 2127-2134.
Nilius, B., Appendino, G., & Owsianik, G. (2012). The transient receptor potential channel
TRPA1: from gene to pathophysiology. Pflügers Archiv-European Journal of Physiology, 464, 425-458.
Okumura, R., Shima, K., Muramatsu, T., Nakagawa, K. I., Shimono, M., Suzuki, T., ... &
Shibukawa, Y. (2005). The odontoblast as a sensory receptor cell? The expression of TRPV1 (VR-1)
channels. Archives of histology and cytology, 68(4), 251-257.
Omar, S., Clarke, R., Abdullah, H., Brady, C., Corry, J., Winter, H., ... & Cosby, S. L. (2017).
Respiratory virus infection up-regulates TRPV1, TRPA1 and ASICS3 receptors on airway cells. PloS
one, 12(2), e0171681.
Osada, A., Hitomi, S., Nakajima, A., Hayashi, Y., Shibuta, I., Tsuboi, Y., ... & Shinoda, M.
(2022). Periodontal acidification contributes to tooth pain hypersensitivity during orthodontic tooth
movement. Neuroscience Research, 177, 103-110.
Roper, S. D. (2014). TRPs in taste and chemesthesis. Mammalian Transient Receptor Potential
(TRP) Cation Channels: Volume II, 827–871.
Maaroufi, H. (2021). Interactions of SARS-CoV-2 spike protein and transient receptor potential
(TRP) cation channels could explain smell, taste, and/or chemesthesis disorders—arXiv preprint
arXiv:2101.06294.
Marincsák, R., Tóth, B. I., Czifra, G., Márton, I., Rédl, P., Tar, I., ... & Bíró, T. (2009). Increased
expression of TRPV1 in squamous cell carcinoma of the human tongue. Oral diseases, 15(5), 328-335.
McKnight, C. A., Diehl, L. J., & Bergin, I. L. (2024). Digestive Tract and Salivary Glands.
In Haschek and Rousseaux's Handbook of Toxicologic Pathology (pp. 1-148). Academic Press.
Moayedi, Y., Michlig, S., Park, M., Koch, A., & Lumpkin, E. A. (2022). Localization of TRP
channels in healthy oral mucosa from human donors. eneuro, 9(6).
Nadezhdin, K. D., Neuberger, A., Nikolaev, Y. A., Murphy, L. A., Gracheva, E. O., Bagriantsev,
S. N., & Sobolevsky, A. I. (2021). Extracellular cap domain is an essential component of the TRPV1
gating mechanism. Nature communications, 12(1), 2154.
Nanjo, Y., Okuma, T., Kuroda, Y., Hayakawa, E., Shibayama, K., Akimoto, T., ... & Takahashi,
K. (2022). Multiple Types of Taste Disorders among Patients with COVID-19. Internal Medicine,
61(14), 2127-2134.
Nilius, B., Appendino, G., & Owsianik, G. (2012). The transient receptor potential channel
TRPA1: from gene to pathophysiology. Pflügers Archiv-European Journal of Physiology, 464, 425-458.
Okumura, R., Shima, K., Muramatsu, T., Nakagawa, K. I., Shimono, M., Suzuki, T., ... &
Shibukawa, Y. (2005). The odontoblast as a sensory receptor cell? The expression of TRPV1 (VR-1)
channels. Archives of histology and cytology, 68(4), 251-257.
Omar, S., Clarke, R., Abdullah, H., Brady, C., Corry, J., Winter, H., ... & Cosby, S. L. (2017).
Respiratory virus infection up-regulates TRPV1, TRPA1 and ASICS3 receptors on airway cells. PloS
one, 12(2), e0171681.
Osada, A., Hitomi, S., Nakajima, A., Hayashi, Y., Shibuta, I., Tsuboi, Y., ... & Shinoda, M.
(2022). Periodontal acidification contributes to tooth pain hypersensitivity during orthodontic tooth
movement. Neuroscience Research, 177, 103-110.
Roper, S. D. (2014). TRPs in taste and chemesthesis. Mammalian Transient Receptor Potential
(TRP) Cation Channels: Volume II, 827–871.
pág. 3553
Samanta, A., Hughes, T. E., & Moiseenkova-Bell, V. Y. (2018). Transient receptor potential
(TRP) channels. Membrane protein complexes: Structure and function, 141-165.
Santoni, G., Santoni, M., Maggi, F., Marinelli, O., & Morelli, M. B. (2020). Emerging role of
mucolipins TRPML channels in cancer. Frontiers in Oncology, 10, 659.
Saunders, C. J., Li, W. Y., Patel, T. D., Muday, J. A., & Silver, W. L. (2013). Dissecting the
role of TRPV1 in detecting multiple trigeminal irritants in three behavioral assays for sensory irritation.
F1000Research, 2.
Sawicki, C. M., Janal, M. N., Nicholson, S. J., Wu, A. K., Schmidt, B. L., & Albertson, D. G.
(2022). Oral cancer patients experience mechanical and chemical sensitivity at the site of the
cancer. BMC cancer, 22(1), 1165.
Scheff, N. N., Wall, I. M., Nicholson, S., Williams, H., Chen, E., Tu, N. H., ... & Schmidt, B.
L. (2022). Oral cancer induced TRPV1 sensitization is mediated by PAR2 signaling in primary afferent
neurons innervating the cancer microenvironment. Scientific reports, 12(1), 4121.
Semmo, M., Köttgen, M., & Hofherr, A. (2014). The TRPP subfamily and polycystin-1 proteins.
Mammalian Transient Receptor Potential (TRP) Cation Channels: Volume I, 675-711.
Smutzer, G., & Devassy, R. K. (2016). Integrating TRPV1 receptor function with capsaicin
psychophysics. Advances in Pharmacological and Pharmaceutical Sciences, 2016(1), 1512457.
Sooampon, S., Phoolcharoen, W., & Pavasant, P. (2013). Thermal stimulation of TRPV1 up-
regulates TNFα expression in human periodontal ligament cells. Archives of Oral Biology, 58(7), 887–
895.
Takahashi, N., Matsuda, Y., Yamada, H., Tabeta, K., Nakajima, T., Murakami, S., & Yamazaki,
K. (2014). Epithelial TRPV1 signaling accelerates gingival epithelial cell proliferation. Journal of
Dental Research, 93(11), 1141-1147.
Takahashi, N., Tsuzuno, T., Mineo, S., Yamada-Hara, M., Aoki-Nonaka, Y., & Tabeta, K. (2020).
Epithelial TRPV1 channels: expression, function, and pathogenicity in the oral cavity. Journal of Oral
Biosciences, 62(3), 235-241.
Tsuchiya, H. (2023). COVID-19 oral sequelae: persistent gustatory and saliva secretory
dysfunctions after recovery from Covid-19. Medical Principles and Practice, 32(3), 166.
Samanta, A., Hughes, T. E., & Moiseenkova-Bell, V. Y. (2018). Transient receptor potential
(TRP) channels. Membrane protein complexes: Structure and function, 141-165.
Santoni, G., Santoni, M., Maggi, F., Marinelli, O., & Morelli, M. B. (2020). Emerging role of
mucolipins TRPML channels in cancer. Frontiers in Oncology, 10, 659.
Saunders, C. J., Li, W. Y., Patel, T. D., Muday, J. A., & Silver, W. L. (2013). Dissecting the
role of TRPV1 in detecting multiple trigeminal irritants in three behavioral assays for sensory irritation.
F1000Research, 2.
Sawicki, C. M., Janal, M. N., Nicholson, S. J., Wu, A. K., Schmidt, B. L., & Albertson, D. G.
(2022). Oral cancer patients experience mechanical and chemical sensitivity at the site of the
cancer. BMC cancer, 22(1), 1165.
Scheff, N. N., Wall, I. M., Nicholson, S., Williams, H., Chen, E., Tu, N. H., ... & Schmidt, B.
L. (2022). Oral cancer induced TRPV1 sensitization is mediated by PAR2 signaling in primary afferent
neurons innervating the cancer microenvironment. Scientific reports, 12(1), 4121.
Semmo, M., Köttgen, M., & Hofherr, A. (2014). The TRPP subfamily and polycystin-1 proteins.
Mammalian Transient Receptor Potential (TRP) Cation Channels: Volume I, 675-711.
Smutzer, G., & Devassy, R. K. (2016). Integrating TRPV1 receptor function with capsaicin
psychophysics. Advances in Pharmacological and Pharmaceutical Sciences, 2016(1), 1512457.
Sooampon, S., Phoolcharoen, W., & Pavasant, P. (2013). Thermal stimulation of TRPV1 up-
regulates TNFα expression in human periodontal ligament cells. Archives of Oral Biology, 58(7), 887–
895.
Takahashi, N., Matsuda, Y., Yamada, H., Tabeta, K., Nakajima, T., Murakami, S., & Yamazaki,
K. (2014). Epithelial TRPV1 signaling accelerates gingival epithelial cell proliferation. Journal of
Dental Research, 93(11), 1141-1147.
Takahashi, N., Tsuzuno, T., Mineo, S., Yamada-Hara, M., Aoki-Nonaka, Y., & Tabeta, K. (2020).
Epithelial TRPV1 channels: expression, function, and pathogenicity in the oral cavity. Journal of Oral
Biosciences, 62(3), 235-241.
Tsuchiya, H. (2023). COVID-19 oral sequelae: persistent gustatory and saliva secretory
dysfunctions after recovery from Covid-19. Medical Principles and Practice, 32(3), 166.
pág. 3554
Tynan, A., Tsaava, T., Gunasekaran, M., Bravo Iñiguez, C. E., Brines, M., Chavan, S. S., &
Tracey, K. J. (2024). TRPV1 nociceptors are required to optimize antigen-specific primary antibody
responses to novel antigens. Bioelectronic Medicine, 10(1), 14.
Wen, H., Gwathmey, J. K., & Xie, L. H. (2020). Role of transient receptor potential canonical
channels in heart physiology and pathophysiology. Frontiers in Cardiovascular Medicine, 7, 24.
Wen, W., Que, K., Zang, C., Wen, J., Sun, G., Zhao, Z., & Li, Y. (2017). Expression and
distribution of three transient receptor potential vanilloid (TRPV) channel proteins in human
odontoblast-like cells. Journal of Molecular Histology, 48, 367-377.
Yang, F., & Zheng, J. (2017). Understand spiciness: mechanism of TRPV1 channel activation
by capsaicin. Protein & cell, 8, 169-177.
Xia, M. (2023). Oral and Maxillofacial Anatomy. In Anesthesia for Oral and Maxillofacial
Surgery (pp. 7–26). Singapore: Springer Nature Singapore.
Zhai, K., Liskova, A., Kubatka, P., & Büsselberg, D. (2020). Calcium entry through TRPV1: a
potential target for the regulation of proliferation and apoptosis in cancerous and healthy cells.
International journal of molecular sciences, 21(11), 4177.
Zheng, W., & Wen, H. (2019). Heat activation mechanism of TRPV1: New insights from
molecular dynamics simulation. Temperature, 6(2), 120-131.
Zhang, M., Ma, Y., Ye, X., Zhang, N., Pan, L., & Wang, B. (2023). TRP (transient receptor
potential) ion channel family: Structures, biological functions and therapeutic interventions for
diseases. Signal Transduction and Targeted Therapy, 8(1), 261.
Zieliński, G., Filipiak, Z., Ginszt, M., Matysik-Woźniak, A., Rejdak, R., & Gawda, P. (2021).
The organ of vision and the stomatognathic system—Review of association studies and evidence-based
discussion. Brain Sciences, 12(1), 14.
Tynan, A., Tsaava, T., Gunasekaran, M., Bravo Iñiguez, C. E., Brines, M., Chavan, S. S., &
Tracey, K. J. (2024). TRPV1 nociceptors are required to optimize antigen-specific primary antibody
responses to novel antigens. Bioelectronic Medicine, 10(1), 14.
Wen, H., Gwathmey, J. K., & Xie, L. H. (2020). Role of transient receptor potential canonical
channels in heart physiology and pathophysiology. Frontiers in Cardiovascular Medicine, 7, 24.
Wen, W., Que, K., Zang, C., Wen, J., Sun, G., Zhao, Z., & Li, Y. (2017). Expression and
distribution of three transient receptor potential vanilloid (TRPV) channel proteins in human
odontoblast-like cells. Journal of Molecular Histology, 48, 367-377.
Yang, F., & Zheng, J. (2017). Understand spiciness: mechanism of TRPV1 channel activation
by capsaicin. Protein & cell, 8, 169-177.
Xia, M. (2023). Oral and Maxillofacial Anatomy. In Anesthesia for Oral and Maxillofacial
Surgery (pp. 7–26). Singapore: Springer Nature Singapore.
Zhai, K., Liskova, A., Kubatka, P., & Büsselberg, D. (2020). Calcium entry through TRPV1: a
potential target for the regulation of proliferation and apoptosis in cancerous and healthy cells.
International journal of molecular sciences, 21(11), 4177.
Zheng, W., & Wen, H. (2019). Heat activation mechanism of TRPV1: New insights from
molecular dynamics simulation. Temperature, 6(2), 120-131.
Zhang, M., Ma, Y., Ye, X., Zhang, N., Pan, L., & Wang, B. (2023). TRP (transient receptor
potential) ion channel family: Structures, biological functions and therapeutic interventions for
diseases. Signal Transduction and Targeted Therapy, 8(1), 261.
Zieliński, G., Filipiak, Z., Ginszt, M., Matysik-Woźniak, A., Rejdak, R., & Gawda, P. (2021).
The organ of vision and the stomatognathic system—Review of association studies and evidence-based
discussion. Brain Sciences, 12(1), 14.