Why individual thermo sensation and pain perception varies? Clue of disruptive mutations in TRPVs from 2504 human genome data

Ghosh, Arijit; Kaur, Navneet; Kumar, Abhishek; Goswami, Chandan

doi:10.1080/19336950.2016.1162365

Cited by 18 publications

(12 citation statements)

References 38 publications

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Section: Trp Genetic Variability and Painmentioning

confidence: 99%

“…A systematic analysis by Ghosh et al (2016) examining 2504 genome data suggested high variability in the TRPV family. Mutations in TRPV1 are associated with functional dyspepsia (Ile-315-Met) and decreased risk of asthma (Ile-585-Val) [59]. TRPV1 has also been associated with bone cancer pain; TRPV1 inactivation and TRPV1 gene disruption have been found to decrease pain in animals with bone cancer [60].…”

Section: Trp Genetic Variability and Painmentioning

confidence: 99%

“…TRPV1 has also been associated with bone cancer pain; TRPV1 inactivation and TRPV1 gene disruption have been found to decrease pain in animals with bone cancer [60]. Mutations in the TRPV3 gene result in Olmsted Syndrome, a rare genetic disorder characterized by painful "bilateral mutilating transgredient palmoplantar keratoderma and periorificial keratotic plaques" [59]. TRP4, an osmoreceptor, is activated by innocuous heat (threshold −27 • C), low pH, endocannabinoids, arachidonic acid metabolites, and nitric oxide; TRP4 may also play a role in mechanical hyperalgesia.…”

Section: Trp Genetic Variability and Painmentioning

confidence: 99%

“…Mutations in TRPV4 gene channels result in ion channel dysfunctions and are characterized by motor dysfunctions and neuropathies [57]. These disorders include scapuloperoneal spinal muscular atrophy (Arg-232-Cys) and Charcot-Marie-Tooth disease 2C (Arg-269-His) [57,59]. An Ala-563-Thr mutation in TRPV5 results in an increased Ca 2+ influx and may have an effect on the gating properties of TRPV5 [59].…”

Section: Trp Genetic Variability and Painmentioning

confidence: 99%

“…These disorders include scapuloperoneal spinal muscular atrophy (Arg-232-Cys) and Charcot-Marie-Tooth disease 2C (Arg-269-His) [57,59]. An Ala-563-Thr mutation in TRPV5 results in an increased Ca 2+ influx and may have an effect on the gating properties of TRPV5 [59]. Okamoto et al demonstrated that rs8065080 SNP associated with an amino acid substitution, I585V, was significantly related to elevated capsaicin sensitivity [61].…”

Section: Trp Genetic Variability and Painmentioning

confidence: 99%

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Taste the Pain: The Role of TRP Channels in Pain and Taste Perception

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Jaime-Lara

et al. 2020

IJMS

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Transient receptor potential (TRP) channels are a superfamily of cation transmembrane proteins that are expressed in many tissues and respond to many sensory stimuli. TRP channels play a role in sensory signaling for taste, thermosensation, mechanosensation, and nociception. Activation of TRP channels (e.g., TRPM5) in taste receptors by food/chemicals (e.g., capsaicin) is essential in the acquisition of nutrients, which fuel metabolism, growth, and development. Pain signals from these nociceptors are essential for harm avoidance. Dysfunctional TRP channels have been associated with neuropathic pain, inflammation, and reduced ability to detect taste stimuli. Humans have long recognized the relationship between taste and pain. However, the mechanisms and relationship among these taste–pain sensorial experiences are not fully understood. This article provides a narrative review of literature examining the role of TRP channels on taste and pain perception. Genomic variability in the TRPV1 gene has been associated with alterations in various pain conditions. Moreover, polymorphisms of the TRPV1 gene have been associated with alterations in salty taste sensitivity and salt preference. Studies of genetic variations in TRP genes or modulation of TRP pathways may increase our understanding of the shared biological mediators of pain and taste, leading to therapeutic interventions to treat many diseases.

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Section: Trp Genetic Variability and Painmentioning

confidence: 99%

Section: Trp Genetic Variability and Painmentioning

confidence: 99%

Section: Trp Genetic Variability and Painmentioning

confidence: 99%

Section: Trp Genetic Variability and Painmentioning

confidence: 99%

Section: Trp Genetic Variability and Painmentioning

confidence: 99%

See 3 more Smart Citations

Taste the Pain: The Role of TRP Channels in Pain and Taste Perception

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Jaime-Lara

et al. 2020

IJMS

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Ratio of Hydrophobic–Hydrophilic and Positive–Negative Residues at Lipid–Water-Interface Influences Surface Expression and Channel Gating of TRPV1

et al. 2022

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During evolution, TRPV1 has lost, retained or selected certain residues at Lipid-Water-Interface (LWI) and formed specific patterns there. The ratio of "hydrophobic-hydrophilic" and "positive-negative charged" residues at the inner LWI remains conserved throughout vertebrate evolution and play important role in regulating TRPV1 trafficking, localization and functions. Arg575 is an important residue as Arg575Asp mutant has reduced Capsaicin-sensitivity, surface expression, colocalization with lipid-raft markers, cell area, and increased cell lethality. This lethality is due to the disruption of the ratio between positive-negative charges there. Such lethality can be rescued by either using TRPV1-specfic inhibitor 5'-IRTX or by restoring the positive-negative charge ratio at that position, i.e. by introducing Asp576Arg mutation in Arg575Asp backbone. We propose that Arg575Asp mutant confers TRPV1 in a "constitutive-open-like" condition. These findings have broader implication in understanding the molecular basis of thermo-gating and channel-gating and the microenvironments involved in such process that goes erratic in different diseases.

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Residues of TRPM8 at the Lipid-Water-Interface have Coevolved with Cholesterol Interaction and are Relevant for Diverse Health Disorders

Shikha,

Dalai,

Kumar

et al. 2024

J Membrane Biol

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TRPM8 is a non-selective cation channel that is expressed in several tissues and cells and also has a unique property to be activated by low-temperature. In this work, we have analyzed the conservation of amino acids that are present in the lipid-water-interface (LWI) region of TRPM8, the region which experiences a microenvironment near the membrane surface. We demonstrate that the amino acids present in the LWI region are more conserved than the transmembrane or even full-length TRPM8, suggesting strong selection pressure in these residues. TRPM8 also has several conserved cholesterol-binding motifs where cholesterol can bind in different modes and energies. We suggest that mutations and/or physiological conditions can potentially alter these TRPM8-cholesterol complexes and can lead to physiological disorders or even apparently irreversible diseases such as cancer and neurodegeneration. Graphical abstract

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Why individual thermo sensation and pain perception varies? Clue of disruptive mutations in TRPVs from 2504 human genome data

Cited by 18 publications

References 38 publications

Taste the Pain: The Role of TRP Channels in Pain and Taste Perception

Taste the Pain: The Role of TRP Channels in Pain and Taste Perception

Ratio of Hydrophobic–Hydrophilic and Positive–Negative Residues at Lipid–Water-Interface Influences Surface Expression and Channel Gating of TRPV1

Residues of TRPM8 at the Lipid-Water-Interface have Coevolved with Cholesterol Interaction and are Relevant for Diverse Health Disorders

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