Specialized cutaneous Schwann cells initiate pain sensation

Science ◽  
2019 ◽  
Vol 365 (6454) ◽  
pp. 695-699 ◽  
Author(s):  
Hind Abdo ◽  
Laura Calvo-Enrique ◽  
Jose Martinez Lopez ◽  
Jianren Song ◽  
Ming-Dong Zhang ◽  
...  
Keyword(s):  
Sensory Nerve ◽  
Physiological Role ◽  
Pain Sensation ◽  
Cell Type ◽  
Mechanical Sensitivity ◽  
Functional Connection ◽  
Current Belief ◽  
Nociceptive Information ◽  
Noxious Stimuli ◽  
Essential Prerequisite

An essential prerequisite for the survival of an organism is the ability to detect and respond to aversive stimuli. Current belief is that noxious stimuli directly activate nociceptive sensory nerve endings in the skin. We discovered a specialized cutaneous glial cell type with extensive processes forming a mesh-like network in the subepidermal border of the skin that conveys noxious thermal and mechanical sensitivity. We demonstrate a direct excitatory functional connection to sensory neurons and provide evidence of a previously unknown organ that has an essential physiological role in sensing noxious stimuli. Thus, these glial cells, which are intimately associated with unmyelinated nociceptive nerves, are inherently mechanosensitive and transmit nociceptive information to the nerve.

scholarly journals The input-output relation of primary nociceptive neurons is determined by the morphology of the peripheral nociceptive terminals

2020 ◽  
Author(s):  
Omer Barkai ◽  
Rachely Butterman ◽  
Ben Katz ◽  
Shaya Lev ◽  
Alexander M. Binshtok
Keyword(s):  
Action Potential ◽  
Input Output ◽  
Pain Sensation ◽  
Action Potential Firing ◽  
Nociceptive Neurons ◽  
Pathological Conditions ◽  
Potential Firing ◽  
Noxious Stimuli ◽  
The Individual ◽  
Neuronal Output

AbstractThe output from the peripheral terminals of primary nociceptive neurons, which detect and encode the information regarding noxious stimuli, is crucial in determining pain sensation. The nociceptive terminal endings are morphologically complex structures assembled from multiple branches of different geometry, which converge in a variety of forms to create the terminal tree. The output of a single terminal is defined by the properties of the transducer channels producing the generation potentials and voltage-gated channels, translating the generation potentials into action potential firing. However, in the majority of cases, noxious stimuli activate multiple terminals; thus, the output of the nociceptive neuron is defined by the integration and computation of the inputs of the individual terminals. Here we used a computational model of nociceptive terminal tree to study how the architecture of the terminal tree affects input-output relation of the primary nociceptive neurons. We show that the input-output properties of the nociceptive neurons depend on the length, the axial resistance, and location of individual terminals. Moreover, we show that activation of multiple terminals by capsaicin-like current allows summation of the responses from individual terminals, thus leading to increased nociceptive output. Stimulation of terminals in simulated models of inflammatory or nociceptive hyperexcitability led to a change in the temporal pattern of action potential firing, emphasizing the role of temporal code in conveying key information about changes in nociceptive output in pathological conditions, leading to pain hypersensitivity.Significance statementNoxious stimuli are detected by terminal endings of the primary nociceptive neurons, which are organized into morphologically complex terminal trees. The information from multiple terminals is integrated along the terminal tree, computing the neuronal output, which propagates towards the CNS, thus shaping the pain sensation. Here we revealed that the structure of the nociceptive terminal tree determines the output of the nociceptive neurons. We show that the integration of noxious information depends on the morphology of the terminal trees and how this integration and, consequently, the neuronal output change under pathological conditions. Our findings help to predict how nociceptive neurons encode noxious stimuli and how this encoding changes in pathological conditions, leading to pain.

scholarly journals Uncoupling proteins in mitochondria of plants and some microorganisms.

2001 ◽  
Vol 48 (1) ◽  
pp. 145-155 ◽  
Author(s):  
W Jarmuszkiewicz
Keyword(s):  
Higher Plants ◽  
Uncoupling Protein ◽  
Physiological Role ◽  
Acanthamoeba Castellanii ◽  
Uncoupling Proteins ◽  
Protein Activity ◽  
Functional Connection ◽  
Mitochondrial Inner Membrane ◽  
Mitochondrial Carrier Family

Uncoupling proteins, members of the mitochondrial carrier family, are present in mitochondrial inner membrane and mediate free fatty acid-activated, purine-nucleotide-inhibited H+ re-uptake. Since 1995, it has been shown that the uncoupling protein is present in many higher plants and some microorganisms like non-photosynthetic amoeboid protozoon, Acanthamoeba castellanii and non-fermentative yeast Candida parapsilosis. In mitochondria of these organisms, uncoupling protein activity is revealed not only by stimulation of state 4 respiration by free fatty acids accompanied by decrease in membrane potential (these effects being partially released by ATP and GTP) but mainly by lowering ADP/O ratio during state 3 respiration. Plant and microorganism uncoupling proteins are able to divert very efficiently energy from oxidative phosphorylation, competing for deltamicroH+ with ATP synthase. Functional connection and physiological role of uncoupling protein and alternative oxidase, two main energy-dissipating systems in plant-type mitochondria, are discussed.

scholarly journals The effect of inositol 1,3,4,5-tetrakisphosphate on inositol trisphosphate-induced Ca2+ mobilization in freshly isolated and cultured mouse lacrimal acinar cells

2000 ◽  
Vol 347 (1) ◽  
pp. 77-82 ◽  
Author(s):  
Peter M. SMITH ◽  
Alexander R. HARMER ◽  
Andrew J. LETCHER ◽  
Robin F. IRVINE
Keyword(s):  
Cultured Cells ◽  
Physiological Role ◽  
Cell Type ◽  
Isolated Cells ◽  
Calcium Store ◽  
Inositol Polyphosphates ◽  
Order Of Magnitude ◽  
Lacrimal Acinar Cells ◽  
Experimental Difference ◽  
Stimulation Of

Earlier reports have shown a remarkable synergism between InsP4 and InsP3 [either Ins(1,4,5)P3 or Ins(2,4,5)P3] in activating Ca2+-dependent K+ and Cl- currents in mouse lacrimal cells [Changya, Gallacher, Irvine, Potter and Petersen (1989) J. Membr. Biol. 109, 85-93; Smith (1992) Biochem. J. 283, 27-30]. However, Bird, Rossier, Hughes, Shears, Armstrong and Putney [(1991) Nature (London) 352, 162-165] reported that they could see no such synergism in the same cell type. A major experimental difference between the two laboratories lies in whether or not the cells were maintained in primary culture before use. Here we have compared directly the responses to inositol polyphosphates in freshly isolated cells versus cells cultured for 6-72 h. In the cultured cells, Ins(2,4,5)P3 at 100 μM produced a robust stimulation of K+ and Cl- currents, as much as an order of magnitude greater than that observed in the freshly isolated cells. However, the freshly isolated cells could be restored to a sensitivity similar to cultured cells by the addition of InsP4 at a concentration two orders of magnitude lower than that of Ins(2,4,5)P3. We discuss the implications of this with respect to the actions of InsP4, including the possibility that disruption of the cellular structure during the isolation of the cells exposes an extreme manifestation of a possible physiological role for InsP4 in controlling calcium-store integrity.

scholarly journals Evolutionarily conserved roles of Caenorhabditis elegans perilipin in lipolysis

2019 ◽  
Author(s):  
Filip Kaššák ◽  
Ahmed A Chughtai ◽  
Marta Kostrouchová
Keyword(s):  
Neutral Lipids ◽  
Physiological Role ◽  
Hormone Sensitive Lipase ◽  
Functional Connection ◽  
Regulatory Pathways ◽  
C Elegans ◽  
Evolutionarily Conserved ◽  
Eukaryotic Organisms

Neutral lipids and namely triacyl-glycerols (TAGs) are the prevalent excess energy storage molecules in all eukaryotic organisms. They are universally organized in active cytoplasmic organelles called lipid droplets (LDs) and their breakdown is performed and regulated in an evolutionarily conserved manner. In mammals, two distinct but inter-connected pathways are believed to mediate this catabolism: conventional cytoplasmic lipolysis with effector neutral lipases; and lipophagy, a specific kind of autophagy exploiting lysosomal acidic lipases. Central molecules in this regulation are LD-resident proteins, perilipins (PLINs). Our recent discovery of a sole PLIN orthologue in C. elegans offers a unique opportunity to study these regulatory pathways, provided that the interactive mechanisms are orthologous. To determine this, we employed classical genetics with genome editing tools and in vivo microscopy to provide three lines of evidence demonstrating the conserved role of the C. elegans perilipin. Firstly, we proved the common presence of a standard lipolytic apparatus on LDs. Next, we ascertained a functional connection between nematode PLIN-1 and the effector enzyme, hormone-sensitive lipase (HOSL-1). Finally, we identified lipophagy as a secondary lipolytic pathway, which is consistent with the mammalian model. Our data provide not only a proof of concept but also suggests interesting implications by questioning the physiological role of lipophagy in lipolysis.

scholarly journals NEUROMODULATOR LIGAND-RECEPTOR SYSTEM TIP39 - PTH2R

2020 ◽  
Vol 10 (2) ◽  
pp. 78-85
Author(s):  
A. N. Kurzanov ◽  
I. M. Bykov
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Signal Transmission ◽  
Physiological Role ◽  
Receptor System ◽  
Axon Terminals ◽  
Nociceptive Information ◽  
The Central Nervous System ◽  
Anxiety Depression

Widely spread axon terminals of TIP39 neurons have a distribution similar to PTH2R containing neurons and their fibers which provides an anatomic base of neuromodulation action of TIP39. This functional and anatomic link- ing lets state that TIP39 and PTH2R form a neuromodulator ligand-receptor system. Basing on mechanisms of signal transmission used by TIP39 and PTH2R, they can form a neuromodulator system in many brain parts. TIP39-PTH2R system is a unique neuropeptide-receptor system, which localization and functions in the central nervous system differ from any other neuropeptides. Neuromodulator system TIP39-PTH2R predominantly participates in neuroendocrinal modulation by affecting the endocrinal system by means of its presence in several areas of hypothalamus. TIP39 influences neurons that contain somatostatin and corticotropin-releasing hormone. TIP39 can affect the release of adrenocorticotropin, luteinizing hormone, growth hormone and arginine-vasopressin from hypophysis. Experimental data prove that TIP39 modulates regulatory network of anxiety and depression, several aspects of stress reaction and also controls body temperature, participates in processing of auditory and nociceptive information. Physiological role of TIP39-PTH2R system is still to some extent unknown. However, distribution of PTH2R and TIP39 in tissues outside central nervous system assumes other potential physiological effects for this signal way. It is assumed that TIP39- PTH2R system should be probably considered as a potential therapeutic target for treatment of anxiety, depression and chronic pain, control and correction of neuroendocrine disruptions.

Invertebrate Nociception

2017 ◽  
Author(s):  
Nathaniel J. Himmel ◽  
Atit A. Patel ◽  
Daniel N. Cox
Keyword(s):  
Neuropathic Pain ◽  
Action Potentials ◽  
Behavioral Responses ◽  
Fruit Fly ◽  
High Threshold ◽  
Protective Mechanism ◽  
Pain Sensation ◽  
Current State ◽  
Noxious Stimuli ◽  
Nematode Worm

Nociception is a protective mechanism that mediates behavioral responses to a range of potentially damaging stimuli, including noxious temperature, chemicals, and mechanical stimulation. Nociceptive mechanisms are found throughout metazoans. Noxious stimuli are transduced by specialized, high-threshold peripheral nociceptors, which fire action potentials to elicit adaptive behavioral responses. Nociception is essential for survival and provides a mechanism for sensory perception of noxious stimuli, which alerts the organism to potential environmental dangers. When coupled with pain sensation and complex behavioral responses, this mechanism protects the organism from incipient damage. Moreover, acute and chronic pain may manifest as altered nociception in neuropathic pain states. Elucidating the neural bases of nociception is therefore important for identifying and implementing novel strategies for the treatment of neuropathic pain, as well as uncovering the mechanistic bases by which the nervous system integrates information to produce specific behaviors in response to a range of noxious stimuli. Invertebrate organisms, such as Drosophila melanogaster and Caenorhabditis elegans, have emerged as powerful, genetically tractable platforms for exploring these questions. Here, we concisely review the current state of knowledge regarding the cells, molecules, neural circuits, and behaviors associated with invertebrate nociception in the fruit fly and nematode worm.

scholarly journals Chloride Channels in Astrocytes: Structure, Roles in Brain Homeostasis and Implications in Disease

2019 ◽  
Vol 20 (5) ◽  
pp. 1034 ◽  
Author(s):  
Xabier Elorza-Vidal ◽  
Héctor Gaitán-Peñas ◽  
Raúl Estévez
Keyword(s):  
Chloride Channels ◽  
3D Structure ◽  
Physiological Role ◽  
Anion Channel ◽  
Cell Type ◽  
Multiple Functions ◽  
Voltage Dependent ◽  
Key Aspects ◽  
Brain Homeostasis

Astrocytes are the most abundant cell type in the CNS (central nervous system). They exert multiple functions during development and in the adult CNS that are essential for brain homeostasis. Both cation and anion channel activities have been identified in astrocytes and it is believed that they play key roles in astrocyte function. Whereas the proteins and the physiological roles assigned to cation channels are becoming very clear, the study of astrocytic chloride channels is in its early stages. In recent years, we have moved from the identification of chloride channel activities present in astrocyte primary culture to the identification of the proteins involved in these activities, the determination of their 3D structure and attempts to gain insights about their physiological role. Here, we review the recent findings related to the main chloride channels identified in astrocytes: the voltage-dependent ClC-2, the calcium-activated bestrophin, the volume-activated VRAC (volume-regulated anion channel) and the stress-activated Maxi-Cl−. We discuss key aspects of channel biophysics and structure with a focus on their role in glial physiology and human disease.

scholarly journals Repetitive noxious stimuli during early development affect acute and long-term mechanical sensitivity in rats

2019 ◽  
Vol 87 (1) ◽  
pp. 26-31 ◽  
Author(s):  
N. J. van den Hoogen ◽  
J. Patijn ◽  
D. Tibboel ◽  
E. A. Joosten
Keyword(s):  
Early Development ◽  
Mechanical Sensitivity ◽  
Noxious Stimuli

scholarly journals Cell-Type-Specific Recruitment of Amygdala Interneurons to Hippocampal Theta Rhythm and Noxious Stimuli In Vivo

Neuron ◽  
2012 ◽  
Vol 74 (6) ◽  
pp. 1059-1074 ◽  
Author(s):  
Thomas C.M. Bienvenu ◽  
Daniela Busti ◽  
Peter J. Magill ◽  
Francesco Ferraguti ◽  
Marco Capogna
Keyword(s):  
Theta Rhythm ◽  
Cell Type ◽  
Hippocampal Theta Rhythm ◽  
Cell Type Specific ◽  
Noxious Stimuli ◽  
Hippocampal Theta

Physiological Studies of Spinohypothalamic Tract Neurons in the Lumbar Enlargement of Monkeys

1999 ◽  
Vol 82 (2) ◽  
pp. 1054-1058 ◽  
Author(s):  
X. Zhang ◽  
H. N. Wenk ◽  
A. P. Gokin ◽  
C. N. Honda ◽  
G. J. Giesler
Keyword(s):  
Dorsal Horn ◽  
Receptive Fields ◽  
Antidromic Activation ◽  
Response Characteristics ◽  
Nociceptive Information ◽  
Anatomic Results ◽  
Noxious Stimuli ◽  
Pass Through ◽  
Low Amplitude

Recent anatomic results indicate that a large direct projection from the spinal cord to the hypothalamus exists in monkeys. The aim of this study was to determine whether the existence of this projection could be confirmed unambiguously using electrophysiological methods and, if so, to determine the response characteristics of primate spinohypothalamic tract (SHT) neurons. Fifteen neurons in the lumbar enlargement of macaque monkeys were antidromically activated using low-amplitude current pulses in the contralateral hypothalamus. The points at which antidromic activation thresholds were lowest were found in the supraoptic decussation ( n = 13) or in the medial hypothalamus ( n = 2). Recording points were located in the superficial dorsal horn ( n = 1), deep dorsal horn ( n = 10), and intermediate zone ( n = 4). Each of the 12 examined neurons had cutaneous receptive fields on the ipsilateral hindlimb. All neurons responded exclusively or preferentially to noxious stimuli, suggesting that the transmission of nociceptive information is an important role of primate SHT axons. Twelve SHT neurons were also antidromically activated from the thalamus. In all cases, the antidromic latency from the thalamus was shorter than that from the hypothalamus, suggesting that the axons pass through the thalamus then enter the hypothalamus. These results confirm the existence of a SHT in primates and suggest that this projection may contribute to the production of autonomic, neuroendocrine, and emotional responses to noxious stimuli in primates, possibly including humans.

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