scholarly journals Schwann Cell Autocrine and Paracrine Regulatory Mechanisms, Mediated by Allopregnanolone and BDNF, Modulate PKCε in Peripheral Sensory Neurons

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1874 ◽  
Author(s):  
Veronica Bonalume ◽  
Lucia Caffino ◽  
Luca F. Castelnovo ◽  
Alessandro Faroni ◽  
Flavio Giavarini ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Nerve Fibers ◽  
Neuronal Cultures ◽  
Pharmacological Studies ◽  
Pain Chronification ◽  
Type C ◽  
Peripheral Sensory ◽  
Local Release ◽  
Progesterone Metabolite

Protein kinase type C-ε (PKCε) plays important roles in the sensitization of primary afferent nociceptors, such as ion channel phosphorylation, that in turn promotes mechanical hyperalgesia and pain chronification. In these neurons, PKCε is modulated through the local release of mediators by the surrounding Schwann cells (SCs). The progesterone metabolite allopregnanolone (ALLO) is endogenously synthesized by SCs, whereas it has proven to be a crucial mediator of neuron-glia interaction in peripheral nerve fibers. Biomolecular and pharmacological studies on rat primary SCs and dorsal root ganglia (DRG) neuronal cultures were aimed at investigating the hypothesis that ALLO modulates neuronal PKCε, playing a role in peripheral nociception. We found that SCs tonically release ALLO, which, in turn, autocrinally upregulated the synthesis of the growth factor brain-derived neurotrophic factor (BDNF). Subsequently, glial BDNF paracrinally activates PKCε via trkB in DRG sensory neurons. Herein, we report a novel mechanism of SCs-neuron cross-talk in the peripheral nervous system, highlighting a key role of ALLO and BDNF in nociceptor sensitization. These findings emphasize promising targets for inhibiting the development and chronification of neuropathic pain.

Hypoglycemic detection at the portal vein is mediated by capsaicin-sensitive primary sensory neurons

2007 ◽  
Vol 293 (1) ◽  
pp. E96-E101 ◽  
Author(s):  
Satoshi Fujita ◽  
MaryAnn Bohland ◽  
Graciela Sanchez-Watts ◽  
Alan G. Watts ◽  
Casey M. Donovan
Keyword(s):  
Portal Vein ◽  
Sensory Neurons ◽  
Jugular Vein ◽  
Immunohistochemical Analysis ◽  
Nerve Fibers ◽  
Similar Response ◽  
Primary Sensory Neurons ◽  
Calcitonin Gene ◽  
Epinephrine Concentration

To elucidate the type of spinal afferent involved in hypoglycemic detection at the portal vein, we considered the potential role of capsaicin-sensitive primary sensory neurons. Specifically, we examined the effect of capsaicin-induced ablation of portal vein afferents on the sympathoadrenal response to hypoglycemia. Under anesthesia, the portal vein was isolated in rats and either capsaicin (CAP) or the vehicle (CON) solution applied topically. During the same surgery, the carotid artery (sampling) and jugular vein (infusion) were cannulated. One week later, all animals underwent a hyperinsulinemic hypoglycemic clamp, with glucose (variable) and insulin (25 mU·kg−1·min−1) infused via the jugular vein. Systemic hypoglycemia (2.76 ± 0.05 mM) was induced by minute 75 and sustained until minute 105. By design, no significant differences were observed in arterial glucose or insulin concentrations between groups. When hypoglycemia was induced in CON, the plasma epinephrine concentration increased from 0.67 ± 0.05 nM at basal to 36.15 ± 2.32 nM by minute 105. Compared with CON, CAP animals demonstrated an 80% suppression in epinephrine levels by minute 105, 7.11 ± 0.55 nM ( P < 0.001). A similar response to hypoglycemia was observed for norepinephrine, with CAP values suppressed by 48% compared with CON. Immunohistochemical analysis of the portal vein revealed an 85% decrease in the number of calcitonin gene-related peptide-reactive nerve fibers following capsaicin-induced ablation. That the suppression in the sympathoadrenal response was comparable to our previous findings for total denervation of the portal vein indicates that hypoglycemic detection at the portal vein is mediated by capsaicin-sensitive primary sensory neurons.

scholarly journals Exploration of Sensory and Spinal Neurons Expressing GRP in Itch and Pain

2018 ◽  
Author(s):  
Devin M. Barry ◽  
Xue-Ting Liu ◽  
Qianyi Yang ◽  
Xian-Yu Liu ◽  
Xiansi Zeng ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Nerve Fibers ◽  
List Type ◽  
Spinal Neurons ◽  
Genetic Ablation ◽  
Conditional Deletion ◽  
Pain Transmission ◽  
Chronic Pruritus ◽  
Stimulation Of

AbstractGastrin-releasing peptide (GRP) is a putative itch-specific neurotransmitter, but definite evidence in the dorsal root ganglion (DRG) and spinal cord is lacking. We generated and validated a Grp-Cre knock-in (GrpCre-KI) mouse line whereby Grp neurons are genetically labeled. Cre-dependent marking analysis revealed exclusive innervation of the upper epidermis of the skin by GRP fibers. Importantly, optical stimulation of Grp fibers expressing channel rhodopsin (ChR2) in the skin evoked itch but not pain-related scratching behaviors, while conditional deletion of Grp in sensory neurons attenuated non-histaminergic itch. In contrast, intersectional genetic ablation of spinal Grp neurons did not affect itch nor pain transmission. Our study demonstrates a role of GRP in sensory neurons in itch and suggests that GRP sensory neurons are dedicated to itch transmission. GrpCre-KI mice provide a long-sought avenue for investigating peripheral coding mechanism of itch and further interrogation of itch-nerve fibers in the skin under chronic pruritus.HighlightsValidated expression of a Grp-Cre knock-in line in sensory neurons that innervate the skinOpto-activation of Grp sensory neurons evokes itch behaviorConditional deletion of Grp in sensory neurons reduces non-histaminergic itch behaviorIntersectional ablation of Grp spinal neurons does not affect itch or pain behaviors

scholarly journals Itch and Cough – Similar Role of Sensory Nerves in Their Pathogenesis

2020 ◽  
pp. S43-S54
Author(s):  
T. Pecova ◽  
I. Kocan ◽  
R. Vysehradsky ◽  
R. Pecova
Keyword(s):  
Sensory Nerve ◽  
Small Diameter ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Upper Respiratory Tract ◽  
C Fibers ◽  
Afferent Nerves ◽  
Sensory Fibers ◽  
Peripheral Sensory

Itch is the most common chief complaint in patients visiting dermatology clinics and is analogous to cough and also sneeze of the lower and upper respiratory tract, all three of which are host actions trying to clear noxious stimuli. The pathomechanisms of these symptoms are not completely determined. The itch can originate from a variety of etiologies. Itch originates following the activation of peripheral sensory nerve endings following damage or exposure to inflammatory mediators. More than one sensory nerve subtype is thought to subserve pruriceptive itch which includes both unmyelinated C-fibers and thinly myelinated Aδ nerve fibers. There are a lot of mediators capable of stimulating these afferent nerves leading to itch. Cough and itch pathways are mediated by small-diameter sensory fibers. These cough and itch sensory fibers release neuropeptides upon activation, which leads to inflammation of the nerves. The inflammation is involved in the development of chronic conditions of itch and cough. The aim of this review is to point out the role of sensory nerves in the pathogenesis of cough and itching. The common aspects of itch and cough could lead to new thoughts and perspectives in both fields.

Heterogeneous functional expression of calcium channels at sensory and synaptic regions in nodose neurons

1995 ◽  
Vol 73 (2) ◽  
pp. 872-875 ◽  
Author(s):  
D. Mendelowitz ◽  
P. J. Reynolds ◽  
M. C. Andresen
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Sensory Neurons ◽  
Functional Expression ◽  
Sensory Transduction ◽  
Synaptic Terminals ◽  
Central Synapses ◽  
Peripheral Sensory ◽  
Subtype 3

1. In the present study we have taken advantage of the unique anatomy of visceral sensory neurons that enabled us to isolate and examine the role of calcium channel subtypes at the soma, central synaptic terminals, and peripheral sensory endings. 2. N-type calcium channels dominated somatic currents (60%), with lesser (16% and 12%) contributions from P- and L-type channels, respectively, in patch-clamped dispersed nodose neurons using toxins selective for each calcium channel subtype. 3. These toxins also blocked the release of neurotransmitters from these visceral synaptic terminals in a brain stem slice. Similar to the profile at the soma, N-type calcium channels were most responsible for neurotransmission at this central glutamatergic synapse (57%), with P- and L-type channels making small contributions (12% and 11%, respectively). 4. In contrast to the soma and central synapses, these calcium channel toxins failed to affect the sensory transduction at aortic baroreceptor endings. 5. Therefore calcium channel subtypes have dramatically heterogenous distributions in sensory neurons that presumably subserve the specialized functions that occur at different cellular regions.

scholarly journals Dscam1 promotes blood cell survival in Drosophila melanogaster through a dual role in blood cells and neurons

2020 ◽  
Author(s):  
Debra Ouyang ◽  
Xiaoyi Xiao ◽  
Anjeli Mase ◽  
Glenda Li ◽  
Sean Corcoran ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Sensory Neurons ◽  
Adhesion Molecule ◽  
Blood Cells ◽  
Cell Adhesion Molecule ◽  
Dual Role ◽  
Cell Adhesion Molecule 1 ◽  
Peripheral Sensory

AbstractDown Syndrome Cell Adhesion Molecule 1 (Dscam1) is a receptor-like cell adhesion molecule that is conserved across the animal kingdom, but its roles in hematopoiesis remain unknown. Dscam1 related genes in vertebrates and invertebrates are key regulators of neuron morphogenesis and neuronal tiling. In Drosophila, Dscam1 in addition has roles in blood cells (hemocytes) in innate immunity and phagocytosis of pathogens. Given the anatomical and functional role of peripheral sensory neurons as microenvironments for resident hematopoietic sites in the Drosophila larva, we sought to investigate the role of Dscam1 in this context. Interestingly, we find that Dscam1 fills the role of a previously anticipated factor in neuron-hemocyte communication that supports trophic survival: tissue specific silencing of Dscam1 by in vivo RNAi in sensory neurons leads to neuron reduction, which in turn results in reduced hemocyte numbers due to apoptosis. Dscam1 silencing in hemocytes also results in a reduction of hemocytes and increased apoptosis. This cell-autonomous effect of Dscam1 silencing can be mimicked by RNAi silencing of dreadlocks (dock), suggesting that intracellular Dscam1 signaling relies on the adapter protein Dock in this system. Our findings reveal a dual role for Dscam1 in Drosophila hematopoiesis, by promoting survival of the sensory neuron microenvironments that in turn support hemocyte survival, and by promoting survival of hemocytes cell-autonomously. It will be interesting to explore possible functions of vertebrate Dscam1 related genes such as DSCAML1 in blood cells and their trophic survival.

Role of Natriuretic Peptide Receptor Type C in Dahl Salt-Sensitive Hypertensive Rats

Hypertension ◽  
1997 ◽  
Vol 30 (2) ◽  
pp. 177-183 ◽  
Author(s):  
Miki Nagase ◽  
Katsuyuki Ando ◽  
Takeshi Katafuchi ◽  
Akira Kato ◽  
Shigehisa Hirose ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Receptor Type ◽  
Natriuretic Peptide Receptor ◽  
Hypertensive Rats ◽  
Peptide Receptor ◽  
Type C

scholarly journals A9 DORSAL ROOT GANGLIA NEURONAL RESPONSES AND SUBSTANCE P PRODUCTION ARE HIGHER IN MALE MICE

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 10-11
Author(s):  
J Pujo ◽  
G De Palma ◽  
J Lu ◽  
S M Collins ◽  
P Bercik
Keyword(s):  
Abdominal Pain ◽  
Substance P ◽  
Gut Microbiota ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Neuronal Response ◽  
Neuronal Responses ◽  
Visceral Sensitivity ◽  
Germ Free

Abstract Background Abdominal pain is a common complaint in patients with chronic gastrointestinal disorders. Accumulating evidence suggests that gut microbiota is an important determinant of gut function, including visceral sensitivity. Germ-free (GF) mice have been shown to display visceral hypersensitivity, which normalizes after colonization. Sex also appears to play a key role in visceral sensitivity, as women report more abdominal pain than men. Thus, both gut bacteria and sex are important in the regulation of gut nociception, but the underlying mechanisms remain poorly understood. Aims To investigate the role of gut microbiota and sex in abdominal pain. Methods We used primary cultures of sensory neurons from dorsal root ganglia (DRG) of female and male conventionally raised (SPF) or germ-free (GF) mice (7–18 weeks old). To study the visceral afferent activity in vitro, calcium mobilization in DRG sensory neurons was measured by inverted fluorescence microscope using a fluorescent calcium probe Fluo-4 (1mM). Two parameters were considered i) the percentage of responding neurons ii) the intensity of the neuronal response. First, DRG sensory neurons were stimulated by a TRPV1 agonist capsaicin (12.5nM, 125nM and 1.25µM) or by a mixture of G-protein coupled receptors agonist (GPCR: bradykinin, histamine and serotonin; 1µM, 10µM and 100µM). We next measured the neuronal production of substance P and calcitonin gene-related peptide (CGRP), two neuropeptides associated with nociception, in response to capsaicin (1.25µM) or GPCR agonists (100µM) by ELISA and EIA, respectively. Results The percentage of neurons responding to capsaicin and GPCR agonists was similar in male and female SPF and GF mice. However, the intensity of the neuronal response was higher in SPF male compared to SPF female in response to capsaicin (125nM: p=0.0336; 1.25µM: p=0.033) but not to GPCR agonists. Neuronal activation was similar in GF and SPF mice of both sexes after administration of capsaicin or GPCR agonists. Furthermore, substance P and CGRP production by sensory neurons induced by capsaicin or GPCR agonists was similar in SPF and GF mice, regardless of sex. However, while the response to capsaicin was similar, the GPCR agonists-induced production of substance P was higher in SPF male mice compared to SPF females (p=0.003). The GPCR agonists-induced production of CGRP was similar in SPF male and female mice. Conclusions Our data suggest that at the level of DRG neurons, the absence of gut microbiota does not predispose to visceral hypersensitivity. The intensity of DRG neuronal responses to capsaicin and the GPCR agonists-induced production of substance P are higher in male compared to female mice, in contrast to previously published studies in various models of acute and chronic pain. Further studies are thus needed to investigate the role of sex in visceral sensitivity. Funding Agencies CIHR

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