scholarly journals Odontoblast TRPC5 channels signal cold pain in teeth

2021 ◽  
Vol 7 (13) ◽  
pp. eabf5567
Author(s):  
Laura Bernal ◽  
Pamela Sotelo-Hitschfeld ◽  
Christine König ◽  
Viktor Sinica ◽  
Amanda Wyatt ◽  
...  
Keyword(s):  
Relative Sensitivity ◽  
Cellular Component ◽  
Sensory Transduction ◽  
Cold Sensation ◽  
Cold Pain ◽  
Sensing System ◽  
Cold Sensitive ◽  
Cellular Components ◽  
Cold Sensor ◽  
Cold Sensing

Teeth are composed of many tissues, covered by an inflexible and obdurate enamel. Unlike most other tissues, teeth become extremely cold sensitive when inflamed. The mechanisms of this cold sensation are not understood. Here, we clarify the molecular and cellular components of the dental cold sensing system and show that sensory transduction of cold stimuli in teeth requires odontoblasts. TRPC5 is a cold sensor in healthy teeth and, with TRPA1, is sufficient for cold sensing. The odontoblast appears as the direct site of TRPC5 cold transduction and provides a mechanism for prolonged cold sensing via TRPC5’s relative sensitivity to intracellular calcium and lack of desensitization. Our data provide concrete functional evidence that equipping odontoblasts with the cold-sensor TRPC5 expands traditional odontoblast functions and renders it a previously unknown integral cellular component of the dental cold sensing system.

Role of Ih in the firing pattern of mammalian cold thermoreceptor endings

2012 ◽  
Vol 108 (11) ◽  
pp. 3009-3023 ◽  
Author(s):  
Patricio Orio ◽  
Andrés Parra ◽  
Rodolfo Madrid ◽  
Omar González ◽  
Carlos Belmonte ◽  
...  
Keyword(s):  
Skin Temperature ◽  
Neural Coding ◽  
Firing Pattern ◽  
Firing Frequency ◽  
Sensory Transduction ◽  
Nerve Endings ◽  
Subthreshold Resonance ◽  
Cold Sensitive ◽  
Hcn1 Channels

Mammalian peripheral cold thermoreceptors respond to cooling of their sensory endings with an increase in firing rate and modification of their discharge pattern. We recently showed that cultured trigeminal cold-sensitive (CS) neurons express a prominent hyperpolarization-activated current ( Ih), mainly carried by HCN1 channels, supporting subthreshold resonance in the soma without participating in the response to acute cooling. However, peripheral pharmacological blockade of Ih, or characterization of HCN1−/− mice, reveals a deficit in acute cold detection. Here we investigated the role of Ih in CS nerve endings, where cold sensory transduction actually takes place. Corneal CS nerve endings in mice show a rhythmic spiking activity at neutral skin temperature that switches to bursting mode when the temperature is lowered. Ih blockers ZD7288 and ivabradine alter firing patterns of CS nerve endings, lengthening interspike intervals and inducing bursts at neutral skin temperature. We characterized the CS nerve endings from HCN1−/− mouse corneas and found that they behave similar to wild type, although with a lower slope in the firing frequency vs. temperature relationship, thus explaining the deficit in cold perception of HCN1−/− mice. The firing pattern of nerve endings from HCN1−/− mice was also affected by ZD7288, which we attribute to the presence of HCN2 channels in the place of HCN1. Mathematical modeling shows that the firing phenotype of CS nerve endings from HCN1−/− mice can be reproduced by replacing HCN1 channels with the slower HCN2 channels rather than by abolishing Ih. We propose that Ih carried by HCN1 channels helps tune the frequency of the oscillation and the length of bursts underlying regular spiking in cold thermoreceptors, having important implications for neural coding of cold sensation.

scholarly journals Inflammatory and neuropathic cold allodynia are selectively mediated by the neurotrophic factor receptor GFRα3

2016 ◽  
Vol 113 (16) ◽  
pp. 4506-4511 ◽  
Author(s):  
Erika K. Lippoldt ◽  
Serra Ongun ◽  
Geoffrey K. Kusaka ◽  
David D. McKemy
Keyword(s):  
Chronic Pain ◽  
Neurotrophic Factor ◽  
Neutralizing Antibodies ◽  
Tissue Injury ◽  
Cold Sensitivity ◽  
Mechanical Stimuli ◽  
Cold Pain ◽  
Cold Allodynia ◽  
Cold Sensitive ◽  
Striking Contrast

Tissue injury prompts the release of a number of proalgesic molecules that induce acute and chronic pain by sensitizing pain-sensing neurons (nociceptors) to heat and mechanical stimuli. In contrast, many proalgesics have no effect on cold sensitivity or can inhibit cold-sensitive neurons and diminish cooling-mediated pain relief (analgesia). Nonetheless, cold pain (allodynia) is prevalent in many inflammatory and neuropathic pain settings, with little known of the mechanisms promoting pain vs. those dampening analgesia. Here, we show that cold allodynia induced by inflammation, nerve injury, and chemotherapeutics is abolished in mice lacking the neurotrophic factor receptor glial cell line-derived neurotrophic factor family of receptors-α3 (GFRα3). Furthermore, established cold allodynia is blocked in animals treated with neutralizing antibodies against the GFRα3 ligand, artemin. In contrast, heat and mechanical pain are unchanged, and results show that, in striking contrast to the redundant mechanisms sensitizing other modalities after an insult, cold allodynia is mediated exclusively by a single molecular pathway, suggesting that artemin–GFRα3 signaling can be targeted to selectively treat cold pain.

scholarly journals Neurological Assessment Using a Quantitative Sensory Test in Patients with Chronic Unilateral Orofacial Pain

2018 ◽  
Vol 12 (1) ◽  
pp. 53-58
Author(s):  
Talal H Salame ◽  
Antony Blinkhorn ◽  
Zahra Karami
Keyword(s):  
Orofacial Pain ◽  
Pain Clinic ◽  
Research Network ◽  
Research Centre ◽  
P Value ◽  
Cold Sensation ◽  
Cold Pain ◽  
Royal North Shore Hospital ◽  
Warm Sensation ◽  
Thermal Stimuli

Background: Quantitative Sensory Testing (QST) has been used in clinical and experimental settings to establish sensory assessment for different types of pains, and may be a useful tool for the assessment of orofacial pain, but this premise needs to be tested. Objective: The aim of the study was to evaluate responses to thermal stimuli between painful and non-painful facial sites in subjects with orofacial pain using QST. Methods: A total of 60 participants (5o females: 28-83 years; 10 males: 44-81 years) with unilateral orofacial pain were recruited from the Orofacial Pain Clinic at the Pain Management and Research Centre, Royal North Shore Hospital, Sydney, Australia. The study followed the methods of limits of the German Research Network testing four modalities of thermal thresholds, the Warm Sensation, the Cold Sensation, the Heat Pain and the Cold Pain using a TSA-II Neurosensory Analyser. The results were compared to the results from the unaffected side of the same patient on the same area and a single t test statistical analysis was performed, where a p value of less than 0.05 was considered significant. Results: The Mean Difference for Cold Sensation between the pain side and the non-pain side was 0.48 °C ± 1.5 (t= 2.466, p=0.017), 0.68 °C ± 2.04 for Warm Sensation (t= -2.573, p= 0.013), 2.56 °C ± 2.74 for Cold Pain (t= 7.238, p<0.001) and -1.21 °C ± 2.59 for Hot Pain (t= -3.639, p=0.001). Conclusion: The study showed that QST methods using thermal stimuli could be used to evaluate sensory dysfunction in orofacial pain patients using the specific parameters of cool and warm sensation, and cold and hot pain.

scholarly journals Acute corneal epithelial debridement unmasks the corneal stromal nerve responses to ocular stimulation in rats: implications for abnormal sensations of the eye

2017 ◽  
Vol 117 (5) ◽  
pp. 1935-1947 ◽  
Author(s):  
Harumitsu Hirata ◽  
Kamila Mizerska ◽  
Valentina Dallacasagrande ◽  
Victor H. Guaiquil ◽  
Mark I. Rosenblatt
Keyword(s):  
Epithelial Cell ◽  
Sensory Information ◽  
Sensory Transduction ◽  
High Threshold ◽  
Nerve Terminals ◽  
Transduction Mechanisms ◽  
Cell Layers ◽  
Cold Sensitive ◽  
Low Threshold ◽  
Ganglion Neurons

It is widely accepted that the mechanisms for transducing sensory information reside in the nerve terminals. Occasionally, however, studies have appeared demonstrating that similar mechanisms may exist in the axon to which these terminals are connected. We examined this issue in the cornea, where nerve terminals in the epithelial cell layers are easily accessible for debridement, leaving the underlying stromal (axonal) nerves undisturbed. In isoflurane-anesthetized rats, we recorded extracellularly from single trigeminal ganglion neurons innervating the cornea that are excited by ocular dryness and cooling: low-threshold (<2°C cooling) and high-threshold (>2°C) cold-sensitive plus dry-sensitive neurons playing possible roles in tearing and ocular pain. We found that the responses in both types of neurons to dryness, wetness, and menthol stimuli were effectively abolished by the debridement, indicating that their transduction mechanisms lie in the nerve terminals. However, some responses to the cold, heat, and hyperosmolar stimuli in low-threshold cold-sensitive plus dry-sensitive neurons still remained. Surprisingly, the responses to heat in approximately half of the neurons were augmented after the debridement. We were also able to evoke these residual responses and follow the trajectory of the stromal nerves, which we subsequently confirmed histologically. The residual responses always disappeared when the stromal nerves were cut at the limbus, suggesting that the additional transduction mechanisms for these sensory modalities originated most likely in stromal nerves. The functional significance of these residual and enhanced responses from stromal nerves may be related to the abnormal sensations observed in ocular disease. NEW & NOTEWORTHY In addition to the traditional view that the sensory transduction mechanisms exist in the nerve terminals, we report here that the proximal axons (stromal nerves in the cornea from which these nerve terminals originate) may also be capable of transducing sensory information. We arrived at this conclusion by removing the epithelial cell layers of the cornea in which the nerve terminals reside but leaving the underlying stromal nerves undisturbed.

scholarly journals Body temperature and cold sensation during and following exercise under temperate room conditions in cold-sensitive young trained females

2017 ◽  
Vol 5 (20) ◽  
pp. e13465 ◽  
Author(s):  
Naoto Fujii ◽  
Erii Aoki-Murakami ◽  
Bun Tsuji ◽  
Glen P. Kenny ◽  
Kei Nagashima ◽  
...  
Keyword(s):  
Body Temperature ◽  
Cold Sensation ◽  
Cold Sensitive

scholarly journals Peripheral kappa opioid receptor activation drives cold hypersensitivity in mice

2020 ◽  
Author(s):  
Manish K. Madasu ◽  
Loc V. Thang ◽  
Priyanka Chilukuri ◽  
Sree Palanisamy ◽  
Joel S. Arackal ◽  
...  
Keyword(s):  
Calcium Release ◽  
Receptor Activation ◽  
Kappa Opioid Receptor ◽  
Central Administration ◽  
Cold Sensation ◽  
Kappa Opioid ◽  
Cold Pain ◽  
Simultaneous Application ◽  
Cold Hypersensitivity ◽  
Noxious Cold

AbstractNoxious cold sensation is commonly associated with peripheral neuropathies, however, there has been limited progress in understanding the mechanism of cold pain. Transient receptor potential (TRP) A1 channels facilitate the perception of noxious cold at the level of dorsal root ganglia (DRG), where kappa opioid receptors (KOR) are also expressed but have not previously been implicated in cold sensation. Here we identify a new role for KOR in enhancing cold hypersensitivity. First, we show that systemic KOR agonism (U50,488, KOR agonist), significantly potentiates the latency to jump and the number of jumps on the cold plate compared controls at 3°C. Importantly, NorBNI (KOR antagonist) attenuates U50,488-induced cold hypersensitivity. However, the central administration of NorBNI does not block U50,488-induced cold hypersensitivity suggesting that peripheral KOR likely modulate this effect. Furthermore, the peripherally-restricted KOR agonist, ff(nle)r-NH2 also induces cold hypersensitivity. Using fluorescent in situ hybridization, we show that KOR mRNA colocalizes with the transcripts for the cold-activated TRPA1 and TRPM8 channels in DRG. Finally, using calcium imaging in DRG, we show that intracellular calcium release is potentiated during the simultaneous application of a TRPA1 agonist, mustard oil (MO), and a KOR agonist (U50,488), when compared to MO alone. This potentiated calcium response is absent in TRPA1 KO mice. Together our data suggest that KOR-induces cold hypersensitivity through modulation of peripheral TRPA1 channels. These findings indicate that whether activation of peripheral KOR is protective or not may be dependent on the pain modality.

scholarly journals CNGA3 acts as a cold sensor in hypothalamic neurons

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Viktor V Feketa ◽  
Yury A Nikolaev ◽  
Dana K Merriman ◽  
Sviatoslav N Bagriantsev ◽  
Elena O Gracheva
Keyword(s):  
Preoptic Area ◽  
Ground Squirrels ◽  
Cold Sensitivity ◽  
Neuronal Circuitry ◽  
Ictidomys Tridecemlineatus ◽  
Wide Range ◽  
Cold Sensitive ◽  
Thermoregulatory System ◽  
Cold Sensor ◽  
Thermogenic Response

Most mammals maintain their body temperature around 37°C, whereas in hibernators it can approach 0°C without triggering a thermogenic response. The remarkable plasticity of the thermoregulatory system allowed mammals to thrive in variable environmental conditions and occupy a wide range of geographical habitats, but the molecular basis of thermoregulation remains poorly understood. Here we leverage the thermoregulatory differences between mice and hibernating thirteen-lined ground squirrels (Ictidomys tridecemlineatus) to investigate the mechanism of cold sensitivity in the preoptic area (POA) of the hypothalamus, a critical thermoregulatory region. We report that, in comparison to squirrels, mice have a larger proportion of cold-sensitive neurons in the POA. We further show that mouse cold-sensitive neurons express the cyclic nucleotide-gated ion channel CNGA3, and that mouse, but not squirrel, CNGA3 is potentiated by cold. Our data reveal CNGA3 as a hypothalamic cold sensor and a molecular marker to interrogate the neuronal circuitry underlying thermoregulation.

Freeze-Fracture Replication in the Ultrastructure of Blue-Green Algae

1967 ◽  
Vol 25 ◽  
pp. 74-75
Author(s):  
L. V. Leak
Keyword(s):  
Cell Wall ◽  
Electron Microscope ◽  
Green Algae ◽  
Three Dimensional ◽  
Freeze Fracture ◽  
Electron Microscopic ◽  
Photosynthetic Membranes ◽  
Blue Green Algae ◽  
Cell Biol ◽  
Cellular Components

Electron microscopic observations of freeze-fracture replicas of Anabaena cells obtained by the procedures described by Bullivant and Ames (J. Cell Biol., 1966) indicate that the frozen cells are fractured in many different planes. This fracturing or cleaving along various planes allows one to gain a three dimensional relation of the cellular components as a result of such a manipulation. When replicas that are obtained by the freeze-fracture method are observed in the electron microscope, cross fractures of the cell wall and membranes that comprise the photosynthetic lamellae are apparent as demonstrated in Figures 1 & 2.A large portion of the Anabaena cell is composed of undulating layers of cytoplasm that are bounded by unit membranes that comprise the photosynthetic membranes. The adjoining layers of cytoplasm are closely apposed to each other to form the photosynthetic lamellae. Occassionally the adjacent layers of cytoplasm are separated by an interspace that may vary in widths of up to several 100 mu to form intralamellar vesicles.

Mitochondrial Reconstructions Based on Serial Thick Sections and HVEM

1975 ◽  
Vol 33 ◽  
pp. 286-287
Author(s):  
Jerome J. Paulin
Keyword(s):  
Imaging Techniques ◽  
Three Dimensional ◽  
Posterior Pole ◽  
Dimensional Structure ◽  
Stereo Imaging ◽  
Thin Sections ◽  
Anatomical Features ◽  
The Past ◽  
Cellular Components ◽  
Mitochondrial Reticulum

Within the past decade it has become apparent that HVEM offers the biologist a means to explore the three-dimensional structure of cells and/or organelles. Stereo-imaging of thick sections (e.g. 0.25-10 μm) not only reveals anatomical features of cellular components, but also reduces errors of interpretation associated with overlap of structures seen in thick sections. Concomitant with stereo-imaging techniques conventional serial Sectioning methods developed with thin sections have been adopted to serial thick sections (≥ 0.25 μm). Three-dimensional reconstructions of the chondriome of several species of trypanosomatid flagellates have been made from tracings of mitochondrial profiles on cellulose acetate sheets. The sheets are flooded with acetone, gluing them together, and the model sawed from the composite and redrawn.The extensive mitochondrial reticulum can be seen in consecutive thick sections of (0.25 μm thick) Crithidia fasciculata (Figs. 1-2). Profiles of the mitochondrion are distinguishable from the anterior apex of the cell (small arrow, Fig. 1) to the posterior pole (small arrow, Fig. 2).

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