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 Role of MAP kinases in sensory neurons on pain transmission

PAIN RESEARCH ◽  
2005 ◽  
Vol 20 (4) ◽  
pp. 145-152 ◽  
Author(s):  
Noguchi Koichi
Keyword(s):  
Sensory Neurons ◽  
Map Kinases ◽  
Pain Transmission

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 Inhibition of aberrant Hif1α activation delays intervertebral disc degeneration in adult mice

Bone Research ◽  
2022 ◽  
Vol 10 (1) ◽  
Author(s):  
Zuqiang Wang ◽  
Hangang Chen ◽  
Qiaoyan Tan ◽  
Junlan Huang ◽  
Siru Zhou ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Genetic Ablation ◽  
Adult Mice ◽  
Conditional Deletion ◽  
Current Therapies ◽  
Cartilaginous Endplate ◽  
Ivd Degeneration ◽  
Deficient Mice

AbstractThe intervertebral disc (IVD) is the largest avascular tissue. Hypoxia-inducible factors (HIFs) play essential roles in regulating cellular adaptation in the IVD under physiological conditions. Disc degeneration disease (DDD) is one of the leading causes of disability, and current therapies are ineffective. This study sought to explore the role of HIFs in DDD pathogenesis in mice. The findings of this study showed that among HIF family members, Hif1α was significantly upregulated in cartilaginous endplate (EP) and annulus fibrosus (AF) tissues from human DDD patients and two mouse models of DDD compared with controls. Conditional deletion of the E3 ubiquitin ligase Vhl in EP and AF tissues of adult mice resulted in upregulated Hif1α expression and age-dependent IVD degeneration. Aberrant Hif1α activation enhanced glycolytic metabolism and suppressed mitochondrial function. On the other hand, genetic ablation of the Hif1α gene delayed DDD pathogenesis in Vhl-deficient mice. Administration of 2-methoxyestradiol (2ME2), a selective Hif1α inhibitor, attenuated experimental IVD degeneration in mice. The findings of this study show that aberrant Hif1α activation in EP and AF tissues induces pathological changes in DDD, implying that inhibition of aberrant Hif1α activity is a potential therapeutic strategy for DDD.

scholarly journals Sensory neurons contacting the cerebrospinal fluid require the Reissner fiber to detect spinal curvature in vivo

2019 ◽  
Author(s):  
Adeline Orts-Del’Immagine ◽  
Yasmine Cantaut-Belarif ◽  
Olivier Thouvenin ◽  
Julian Roussel ◽  
Asha Baskaran ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cerebrospinal Fluid ◽  
Sensory Neurons ◽  
Critical Role ◽  
Central Canal ◽  
Spinal Curvature ◽  
List Type ◽  
Close Vicinity

SummaryRecent evidence indicate active roles for the cerebrospinal fluid (CSF) on body axis development and morphogenesis of the spine implying CSF-contacting neurons (CSF-cNs) in the spinal cord. CSF-cNs project a ciliated apical extension into the central canal that is enriched in the channel PKD2L1 and enables the detection of spinal curvature in a directional manner. Dorsolateral CSF-cNs ipsilaterally respond to lateral bending while ventral CSF-cNs respond to longitudinal bending. Historically, the implication of the Reissner fiber (RF), a long extracellular thread in the CSF, to CSF-cN sensory functions has remained a subject of debate. Here, we reveal using electron microscopy in zebrafish larvae that the RF is in close vicinity with cilia and microvilli of ventral and dorsolateral CSF-cNs. We investigate in vivo the role of cilia and the Reissner fiber in the mechanosensory functions of CSF-cNs by combining calcium imaging with patch-clamp recordings. We show that disruption of cilia motility affects CSF-cN sensory responses to passive and active curvature of the spinal cord without affecting the Pkd2l1 channel activity. Since ciliary defects alter the formation of the Reissner fiber, we investigated whether the Reissner fiber contributes to CSF-cN mechanosensitivity in vivo. Using a hypomorphic mutation in the scospondin gene that forbids the aggregation of SCO-spondin into a fiber, we demonstrate in vivo that the Reissner fiber per se is critical for CSF-cN mechanosensory function. Our study uncovers that neurons contacting the cerebrospinal fluid functionally interact with the Reissner fiber to detect spinal curvature in the vertebrate spinal cord.Abstract FigureeToCThe role of the Reissner fiber, a long extracellular thread running in the cerebrospinal fluid (CSF), has been since its discovery in 1860 a subject of debate. Orts-Del’Immagine et al. report that the Reissner fiber plays a critical role in the detection of spinal curvature by sensory neurons contacting the CSF.HighlightsSince its discovery, the role of the Reissner fiber has long been a subject of debateMechanoreception in CSF-contacting neurons (CSF-cNs) in vivo requires the Reissner fiberCSF-cN apical extension is in close vicinity of the Reissner fiberCSF-cNs and the Reissner fiber form in vivo a sensory organ detecting spinal curvature

GRP-producing nerves control antral somatostatin and gastrin secretion in pigs

1987 ◽  
Vol 253 (6) ◽  
pp. G767-G774 ◽  
Author(s):  
J. J. Holst ◽  
S. Knuhtsen ◽  
C. Orskov ◽  
T. Skak-Nielsen ◽  
S. S. Poulsen ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Substance P ◽  
Nerve Fibers ◽  
Antral Mucosa ◽  
Nerve Supply ◽  
Vagus Nerves ◽  
Vagus Stimulation ◽  
Gastrin Secretion ◽  
Stimulation Of

By immunohistochemistry, nerve fibers containing gastrin-releasing polypeptide (GRP)-like immunoreactivity were identified close to the somatostatin (SS)-producing cells of the gastric antral mucosa. We, therefore, studied the possible role of GRP in the control of antral SS secretion by use of isolated perfused pig antrum with intact vagus nerve supply. Electrical stimulation of the vagus nerves at 4 Hz increased the antral release of GRP up to 10-fold and increased SS output 2- to 3-fold. Atropine at 10(-6) M had no effect on these responses. Intra-arterial GRP increased SS secretion significantly at 10(-10) M and eightfold at 10(-8) M, whereas gastrin secretion was stimulated significantly at 10(-11) M and maximally at 10(-10) M and inhibited at 10(-8) M. Preperfusion with a GRP antagonist ([D-Arg1,D-Pro2,D-Trp7,9,Leu11]substance P) or Fab fragments of antibodies against GRP abolished the effects of vagus stimulation on gastrin and somatostatin output. Gastrin in concentrations up to 10(-7) M was without effect on SS secretion. We conclude that electrical stimulation of the vagus nerves increases antral SS gastrin secretion and that GRP is a likely transmitter.

Effects of electrical stimulation of the tooth pulp and phrenic nerve fibers on C 1 spinal neurons in the rat

1999 ◽  
Vol 126 (3) ◽  
pp. 351-358 ◽  
Author(s):  
S. Matsumoto ◽  
M. Takeda ◽  
T. Tanimoto
Keyword(s):  
Electrical Stimulation ◽  
Phrenic Nerve ◽  
Nerve Fibers ◽  
Tooth Pulp ◽  
Spinal Neurons ◽  
Stimulation Of

scholarly journals Involvement of Neuro-Immune Interactions in Pruritus With Special Focus on Receptor Expressions

2021 ◽  
Vol 8 ◽  
Author(s):  
Aylin Ruppenstein ◽  
Maren M. Limberg ◽  
Karin Loser ◽  
Andreas E. Kremer ◽  
Bernhard Homey ◽  
...  
Keyword(s):  
Immune Cells ◽  
Skin Diseases ◽  
Treatment Options ◽  
Nerve Fibers ◽  
Special Focus ◽  
Spinal Neurons ◽  
Inflammatory Skin Diseases ◽  
Underlying Causes ◽  
Specific Receptors ◽  
Chronic Pruritus

Pruritus is a common, but very challenging symptom with a wide diversity of underlying causes like dermatological, systemic, neurological and psychiatric diseases. In dermatology, pruritus is the most frequent symptom both in its acute and chronic form (over 6 weeks in duration). Treatment of chronic pruritus often remains challenging. Affected patients who suffer from moderate to severe pruritus have a significantly reduced quality of life. The underlying physiology of pruritus is very complex, involving a diverse network of components in the skin including resident cells such as keratinocytes and sensory neurons as well as transiently infiltrating cells such as certain immune cells. Previous research has established that there is a significant crosstalk among the stratum corneum, nerve fibers and various immune cells, such as keratinocytes, T cells, basophils, eosinophils and mast cells. In this regard, interactions between receptors on cutaneous and spinal neurons or on different immune cells play an important role in the processing of signals which are important for the transmission of pruritus. In this review, we discuss the role of various receptors involved in pruritus and inflammation, such as TRPV1 and TRPA1, IL-31RA and OSMR, TSLPR, PAR-2, NK1R, H1R and H4R, MRGPRs as well as TrkA, with a focus on interaction between nerve fibers and different immune cells. Emerging evidence shows that neuro-immune interactions play a pivotal role in mediating pruritus-associated inflammatory skin diseases such as atopic dermatitis, psoriasis or chronic spontaneous urticaria. Targeting these bidirectional neuro-immune interactions and the involved pruritus-specific receptors is likely to contribute to novel insights into the underlying pathogenesis and targeted treatment options of pruritus.

Primary Cilia of Odontoblasts: Possible Role in Molar Morphogenesis

2009 ◽  
Vol 88 (10) ◽  
pp. 910-915 ◽  
Author(s):  
B. Thivichon-Prince ◽  
M.L. Couble ◽  
A. Giamarchi ◽  
P. Delmas ◽  
B. Franco ◽  
...  
Keyword(s):  
Primary Cilium ◽  
Close Relationships ◽  
Primary Cilia ◽  
Nerve Fibers ◽  
Vertebrate Cell ◽  
Pain Transmission ◽  
Dentin Formation

A primary cilium, a sensory organelle present in almost every vertebrate cell, is regularly described in odontoblasts, projecting from the surfaces of the cells. Based on the hypothesis that the primary cilium is crucial both for dentin formation and possibly in tooth pain transmission, we have investigated the expression and localization of the main cilium components and involvement of the OFD1 gene in tooth morphogenesis. Odontoblasts in vitro express tubulin, inversin, rootletin, OFD1, BBS4, BBS6, ALMS1, KIF3A, PC1, and PC2. In vivo, cilia are aligned parallel to the dentin walls, with the top part oriented toward the pulp core. Close relationships between cilium and nerve fibers are evidenced. Calcium channels are concentrated in the vicinity of the basal body. Analysis of these data suggests a putative role of cilia in sensing the microenvironment, probably related to dentin secretion. This hypothesis is enhanced by the huge defects observed on molars from Ofd1 knockout mice, showing undifferentiated dentin-forming cells.

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.

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