scholarly journals Neuropeptide FF receptor 2 inhibits capsaicin-induced CGRP Upregulation in mouse trigeminal ganglion

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ya-Tin Lin ◽  
Zachary Yu ◽  
Sze-Chi Tsai ◽  
Po-Hung Hsu ◽  
Jin-Chung Chen
Keyword(s):  
Trigeminal Ganglion ◽  
Spontaneous Pain ◽  
Cisterna Magna ◽  
Neuropeptide Ff ◽  
Calcitonin Gene ◽  
Intracisternal Injection ◽  
Cephalic Pain ◽  
The Impact ◽  
Signal Intensity Threshold ◽  
Stimulation Of

Abstract Background Stimulation of trigeminovascular pathway is widely used to establish the headache animal model. Headache is a common neurological disorder, in which symptomatic attacks are mediated by calcitonin-gene-related peptide (CGRP). CGRP is synthesized and released from the trigeminal ganglion to transmit pain signals under stimulation. On the other hand, Neuropeptide FF (NPFF) is a candidate transmitter/modulator for migraine, and stimulation of its receptor, NPFFR2, increases the expression and release of CGRP in mice sensory neurons. Here, we investigate the impact of NPFFR2 on trigeminal CGRP level in a capsaicin-induced headache mouse model. Methods Mice were intracisternally injected with capsaicin into the cisterna magna to activate the trigeminovascular pathway and induce headache symptoms. Mice pretreated with Npffr2-shRNA or NPFFR2 knockouts were adopted to test the impact of NPFFR2 on capsaicin-induced CGRP upregulation in trigeminal ganglion. The gene silencing effect of Npffr2-shRNA in trigeminal ganglion was confirmed by real-time PCR. Trigeminal CGRP level was determined by immunofluorescence staining, and the percentage of CGRP-positive cell was calculated after setting the signal intensity threshold by Image J software. Amount of trigeminal CGRP in NPFFR2 overexpressed mice was also measured by CGRP ELISA. Findings Infusion of capsaicin into the cisterna magna upregulated the CGRP in trigeminal ganglion and induced spontaneous pain behaviors including the reduction of locomotor activity and the increase of freezing behavior. Intracisternal injection of Npffr2-shRNA reduced the mRNA of Npffr2 in trigeminal ganglion. Mice pretreatment with Npffr2-shRNA prevented capsaicin-induced CGRP upregulation in trigeminal ganglion. Similarly, CGRP upregulation was also reduced in NPFFR2 knockout mice. On the contrary, trigeminal CGRP was increased in NPFFR2 overexpressed mice. Conclusions Reducing the level of NPFFR2 leads to the downregulation of capsaicin-induced CGRP in trigeminal ganglion, which would consequently attenuate the activation of trigeminovascular pathway. Thus, NPFFR2 could serve as a potential target for neuromodulation of cephalic pain.

Influence of DAFS-25+polizon composition on blood and functional state of liver of steers at fattening

2020 ◽  
pp. 15-18
Author(s):  
Inna R. Kilmetova ◽  
◽  
Igor A. Rodin ◽  
Nazira I. Khayrullina ◽  
Nikolay G. Fenchenko ◽  
...  
Keyword(s):  
Functional State ◽  
White Blood Cells ◽  
Live Weight ◽  
The Body ◽  
Farm Animals ◽  
Control Group ◽  
Standard Diet ◽  
The Impact ◽  
Experimental Group ◽  
Stimulation Of

Summary. The disbalanced feeding and the uneven distribution of micro- and macroelements in the environment leads to a trace element, in particular hypomelanosis. To accelerate the growth and preservation of young farm animals include in the diet of various biological additives and drugs, which include selenium. For stimulation of weight gain in the livestock industry, as well as for the prevention and treatment of pathological processes in addition to micro - and macrouse amino acids, primarily methionine. The aim of this work was to study the influence of composition of DAFS-25+Polizon on morpho-biochemical parameters of blood and functional state of the liver in fattening bulls of black-motley breed in the conditions of the Republic of Bashkortostan. Experiments using were conducted on bull-calves of black-motley breed of the properties in the properties age from 6 to 15 months. The first experimental group during the experiment was additionally given the composition of DAFS-25+Polizon at a dose of 2 mg/kg, the animals of the control group received a standard diet. To assess the impact of the composition DAFS-25+Polizon on metabolism cattle studied morphological and biochemical indicators of blood and conducted histological examination of the liver. It is established that the use of the composition of DAFS-25+Polizon at a dose of 2 mg/kg increases the number of erythrocytes and hemoglobin in the experimental group and reduces the amount of white blood cells. The serum content of total protein, phosphorus and calcium increases in the group of experimental animals. Microscopic examination of the liver revealed no changes in the structure of the organ and hepatocytes in the experimental group, whereas in the control group hemodynamic disorders and dystrophic changes in liver cells were observed. Thus, the use of the composition DAFS-25+Polizon at a dose of 2 mg/kg of live weight in fattening bulls black-and-white breed contributes to the increase of redox processes in the body, stimulation of metabolism, prevent the development of liver disorders of cellular mechanisms of metabolism, optimizes the structure of the liver, which generally provides higher productivity.

scholarly journals Seeding of breast cancer cell line (MDA-MB-231LUC+) to the mandible induces overexpression of substance P and CGRP throughout the trigeminal ganglion and widespread peripheral sensory neuropathy throughout all three of its divisions

2021 ◽  
Vol 17 ◽  
pp. 174480692110240
Author(s):  
Silvia Gutierrez ◽  
James C Eisenach ◽  
M Danilo Boada
Keyword(s):  
Breast Cancer ◽  
Substance P ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Trigeminal Ganglion ◽  
Breast Cancer Cell Line ◽  
Cancer Cell Line ◽  
The Impact

Some types of cancer are commonly associated with intense pain even at the early stages of the disease. The mandible is particularly vulnerable to metastasis from breast cancer, and this process has been studied using a bioluminescent human breast cancer cell line (MDA-MB-231LUC+). Using this cell line and anatomic and neurophysiologic methods in the trigeminal ganglion (TG), we examined the impact of cancer seeding in the mandible on behavioral evidence of hypersensitivity and on trigeminal sensory neurons. Growth of cancer cells seeded to the mandible after arterial injection of the breast cancer cell line in Foxn1 animals (allogeneic model) induced behavioral hypersensitivity to mechanical stimulation of the whisker pad and desensitization of tactile and sensitization of nociceptive mechanically sensitive afferents. These changes were not restricted to the site of metastasis but extended to sensory afferents in all three divisions of the TG, accompanied by widespread overexpression of substance P and CGRP in neurons through the ganglion. Subcutaneous injection of supernatant from the MDA-MB-231LUC+ cell culture in normal animals mimicked some of the changes in mechanically responsive afferents observed with mandibular metastasis. We conclude that released products from these cancer cells in the mandible are critical for the development of cancer-induced pain and that the overall response of the system greatly surpasses these local effects, consistent with the widespread distribution of pain in patients. The mechanisms of neuronal plasticity likely occur in the TG itself and are not restricted to afferents exposed to the metastatic cancer microenvironment.

Calcitonin gene-related peptide receptors in rat trigeminal ganglion do not control spinal trigeminal activity

2012 ◽  
Vol 108 (2) ◽  
pp. 431-440 ◽  
Author(s):  
Oana Covasala ◽  
Sören L. Stirn ◽  
Stephanie Albrecht ◽  
Roberto De Col ◽  
Karl Messlinger
Keyword(s):  
Trigeminal Ganglion ◽  
Dura Mater ◽  
Calcitonin Gene Related Peptide ◽  
Afferent Input ◽  
Nitric Oxide Donor ◽  
Cgrp Receptor ◽  
Related Peptide ◽  
Trigeminal Neurons ◽  
Calcitonin Gene ◽  
Evoked Activity

Calcitonin gene-related peptide (CGRP) is regarded as a key mediator in the generation of primary headaches. CGRP receptor antagonists reduce migraine pain in clinical trials and spinal trigeminal activity in animal experiments. The site of CGRP receptor inhibition causing these effects is debated. Activation and inhibition of CGRP receptors in the trigeminal ganglion may influence the activity of trigeminal afferents and hence of spinal trigeminal neurons. In anesthetized rats extracellular activity was recorded from neurons with meningeal afferent input in the spinal trigeminal nucleus caudalis. Mechanical stimuli were applied at regular intervals to receptive fields located in the exposed cranial dura mater. α-CGRP (10−5 M), the CGRP receptor antagonist olcegepant (10−3 M), or vehicle was injected through the infraorbital canal into the trigeminal ganglion. The injection of volumes caused transient discharges, but vehicle, CGRP, or olcegepant injection was not followed by significant changes in ongoing or mechanically evoked activity. In animals pretreated intravenously with the nitric oxide donor glyceryl trinitrate (GTN, 250 μg/kg) the mechanically evoked activity decreased after injection of CGRP and increased after injection of olcegepant. In conclusion, the activity of spinal trigeminal neurons with meningeal afferent input is normally not controlled by CGRP receptor activation or inhibition in the trigeminal ganglion. CGRP receptors in the trigeminal ganglion may influence neuronal activity evoked by mechanical stimulation of meningeal afferents only after pretreatment with GTN. Since it has previously been shown that olcegepant applied to the cranial dura mater is ineffective, trigeminal activity driven by meningeal afferent input is more likely to be controlled by CGRP receptors located centrally to the trigeminal ganglion.

scholarly journals Calcitonin gene-related peptide receptor antagonist human CGRP-(8-37)

1989 ◽  
Vol 256 (2) ◽  
pp. E331-E335 ◽  
Author(s):  
T. Chiba ◽  
A. Yamaguchi ◽  
T. Yamatani ◽  
A. Nakamura ◽  
T. Morishita ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Adenylate Cyclase ◽  
Calcitonin Gene Related Peptide ◽  
Human Calcitonin ◽  
Liver Plasma Membrane ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Liver Membranes ◽  
Calcitonin Receptors ◽  
Stimulation Of

From this study, we predicted that the human calcitonin gene-related peptide (hCGRP) fragment hCGRP-(8-37) would be a selective antagonist for CGRP receptors but an agonist for calcitonin (CT) receptors. In rat liver plasma membrane, where CGRP receptors predominate and CT appears to act through these receptors, hCGRP-(8-37) dose dependently displaced 125I-[Tyr0]rat CGRP binding. However, hCGRP-(8-37) had no effect on adenylate cyclase activity in liver plasma membrane. Furthermore, hCGRP-(8-37) inhibited adenylate cyclase activation induced not only by hCGRP but also by hCT. On the other hand, in LLC-PK1 cells, where calcitonin receptors are abundant and CGRP appears to act via these receptors, the bindings of 125I-[Tyr0]rat CGRP and 125I-hCT were both inhibited by hCGRP-(8-37). In contrast to liver membranes, interaction of hCGRP-(8-37) with these receptors led to stimulation of adenosine 3',5'-cyclic monophosphate (cAMP) production in LLC-PK1 cells, and moreover, this fragment did not inhibit the increased production of cAMP induced not only by hCT but also by hCGRP. Thus hCGRP-(8-37) appears to be a useful tool for determining whether the action of CGRP as well as that of CT is mediated via specific CGRP receptors or CT receptors.

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