scholarly journals PROBABLE ANALGESIC EFFECT OF SYNTHETIC TETRAPEPTIDE

2019 ◽  
Vol 19 (1S) ◽  
pp. 172-174
Author(s):  
V B Plakhova ◽  
V A Penniyaynen ◽  
I V Rogachevskii ◽  
S A Podzorova ◽  
E A Merculova ◽  
...  
Keyword(s):  
Analgesic Effect ◽  
Nervous Tissue ◽  
Molecular Mechanisms ◽  
Drug Substance ◽  
Physiological Regeneration ◽  
Activation Gating ◽  
Regeneration Effect

The aim of the study was to elucidate the molecular mechanisms of modulation of the NaV1.8 channels with a synthetic tetrapeptide (Ac-RERR-NH2). Our data suggest that this substance specifically modulates the activation gating device of these channels, which are responsible for coding of pain signals. This agent (0.1 nM) has a neurite-stimulating effect, which indicates its possible physiological regeneration effect on the nervous tissue. The results obtained allow us to conclude that the agent under study can claim to be the drug substance of a safe and effective analgesic.

scholarly journals THE GABA-ERGIC SYSTEM DOES NOT CONTROL THE NOCICEPTIVE RESPONSES OF PRIMARY SENSORY NEURON

2019 ◽  
Vol 19 (1S) ◽  
pp. 44-45
Author(s):  
V A Penniyaynen ◽  
S A Podzorova ◽  
S G Terekhin ◽  
B V Krylov ◽  
V B Plakhova
Keyword(s):  
Sensory Neuron ◽  
Sensory Neurons ◽  
Nervous Tissue ◽  
Molecular Mechanisms ◽  
Primary Sensory Neuron ◽  
Nociceptive Neuron ◽  
Wide Range ◽  
Nociceptive Responses ◽  
Activation Gating

The aim of the study was to elucidate the molecular mechanisms of the interconnection of the GABA-ergic and nociceptive systems at the level of the peripheral division of the CNS. The data obtained indicate that GABA does not affect the activation gating device of the NaV1.8 channel of the primary sensory neuron responsible for coding pain signals.This agent in a wide range of concentrations also does not affect the growth of neurites of sensory neurons of embryonic nervous tissue. These results confirm our assumption, expressed earlier that the asynaptic membrane of the primary nociceptive neuron is not under the control of the GABA-ergic system.

scholarly journals Pulsed Radiofrequency Application at Some Dorsal Root Ganglions Could Cause Drastic Neuromodulation throughout the Whole Body

2017 ◽  
pp. 223-229
Author(s):  
Young-Chang Arai
Keyword(s):  
Dorsal Root Ganglion ◽  
Analgesic Effect ◽  
Dorsal Root ◽  
Nervous Tissue ◽  
Case Series ◽  
Nerve Fibers ◽  
Whole Body ◽  
Intractable Pain ◽  
Pulsed Radiofrequency ◽  
Modified Technique

Background: The modified technique, pulsed radiofrequency (PRF) procedure, applied to nervous tissue has been providing anecdotal benefits for the management of chronic and intractable pain conditions. Although PRF has a neuromodulatory effect instead of thermally lesioning nervous tissue, the mechanism underlying the analgesic effect of PRF has not been fully clarified yet. Objectives: To see the changes of electricallyevoked responses of peripheral A-δ and A-β nerve fibers and the analgesic effect induced by PRF. Study Design: Case series. Setting: Inpatient. Methods: This study investigated how dorsal root ganglion (DRG) PRF influenced electricallyevoked responses of peripheral A-δ and A-β nerve fibers at the treated root ganglion dominating areas in five patients with intractable vertebral metastatic pain. Results: DRG PRF provided sound pain relief for patients with intractable vertebral metastatic pain. PRF application at DRGs had a different effect on electrically-evoked responses of peripheral A-δ and A-β nerve fibers at not only the treated root ganglion dominating areas but also the nontreated root ganglion dominating areas far from the treated root ganglion dominating areas in each patient. Limitation: This report is a case series. Conclusions: PRF application at some peripheral nerves could cause drastic neuromodulation throughout the whole body. Key words: Pulsed radiofrequency, dorsal root ganglion block, neuromodulation

scholarly journals Adult Neural Stem Cells: Basic Research and Production Strategies for Neurorestorative Therapy

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
E. M. Samoilova ◽  
V. A. Kalsin ◽  
N. M. Kushnir ◽  
D. A. Chistyakov ◽  
A. V. Troitskiy ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Nervous Tissue ◽  
Molecular Mechanisms ◽  
Somatic Cells ◽  
Basic Research ◽  
Neural Cells ◽  
Pluripotent State ◽  
Increased Risk ◽  
Object Of Study

Over many decades, constructing genetically and phenotypically stable lines of neural stem cells (NSC) for clinical purposes with the aim of restoring irreversibly lost functions of nervous tissue has been one of the major goals for multiple research groups. The unique ability of stem cells to maintain their own pluripotent state even in the adult body has made them into the choice object of study. With the development of the technology for induced pluripotent stem cells (iPSCs) and direct transdifferentiation of somatic cells into the desired cell type, the initial research approaches based on the use of allogeneic NSCs from embryonic or fetal nervous tissue are gradually becoming a thing of the past. This review deals with basic molecular mechanisms for maintaining the pluripotent state of embryonic/induced stem and reprogrammed somatic cells, as well as with currently existing reprogramming strategies. The focus is on performing direct reprogramming while bypassing the stage of iPSCs which is known for genetic instability and an increased risk of tumorigenesis. A detailed description of various protocols for obtaining reprogrammed neural cells used in the therapy of the nervous system pathology is also provided.

scholarly journals Molecular Mechanisms Underlying the Enhanced Analgesic Effect of Oxycodone Compared to Morphine in Chemotherapy-Induced Neuropathic Pain

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e91297 ◽  
Author(s):  
Karine Thibault ◽  
Bernard Calvino ◽  
Isabelle Rivals ◽  
Fabien Marchand ◽  
Sophie Dubacq ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Analgesic Effect ◽  
Molecular Mechanisms

Modulation of CaV2.3 Calcium Channel Currents by Eugenol

2008 ◽  
Vol 87 (2) ◽  
pp. 137-141 ◽  
Author(s):  
G. Chung ◽  
J.N. Rhee ◽  
S.J. Jung ◽  
J.S. Kim ◽  
S.B. Oh
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Analgesic Effect ◽  
Molecular Mechanisms ◽  
Expression System ◽  
Calcium Currents ◽  
Analgesic Agent ◽  
Patch Clamp Technique ◽  
Whole Cell Patch Clamp ◽  
Channel Currents

Eugenol, a natural congener of capsaicin, is a routine analgesic agent in dentistry. We have recently demonstrated the inhibition of CaV2.2 calcium channel and sodium channel currents to be molecular mechanisms underlying the analgesic effect of eugenol. We hypothesized that CaV2.3 channels are also modulated by eugenol and investigated its mode of action using the whole-cell patch-clamp technique in a heterologous expression system. Eugenol inhibited calcium currents in the E52 cell line, stably expressing the human CaV2.3 calcium channels, where TRPV1 is not endogenously expressed. The extent of current inhibition was not significantly different between naïve E52 cells and TRPV1-expressing E52 cells, suggesting no involvement of TRPV1. In contrast, TRPV1 activation is prerequisite for the inhibition of CaV2.3 calcium channels by capsaicin. The results indicate that eugenol has mechanisms distinct from those of capsaicin for modulating CaV2.3 channels. We suggest that inhibition of CaV2.3 channels by eugenol might contribute to its analgesic effect.

scholarly journals Сentral and peripheral mechanisms of mu-opioid analgesia and tolerance

2020 ◽  
Vol 16 (1) ◽  
pp. 9-20
Author(s):  
Yu. A. Kolesnikov
Keyword(s):  
Analgesic Effect ◽  
Molecular Mechanisms ◽  
Systemic Administration ◽  
Opioid Analgesia ◽  
Mu Opioid ◽  
Nociceptive Information ◽  
Mu Receptors ◽  
Review Reports ◽  
Development Of Tolerance

Objective – An analysis of the basic science and clinical publications found in PubMed, Medline, and Web of Science. The search covered modern laboratory and clinical mechanisms of peripheral mu opioid analgesia, the role of peripheral mu receptors in systemic analgesia and the development of tolerance to the analgesic effect of opioids. The review discusses the regulatory mechanisms of synthesis and transport of mu-opioid receptors in the primary afferent neurons and the molecular mechanisms responsible for modulating the conduction of nociceptive information from the periphery to the spinal cord. According to some authors, the peripheral component can account for 50-90% of the total analgesic effect after the systemic administration of morphine and methadone. The review reports on the important role of glycoprotein-P and the blood-brain barrier transport system in modulating the peripheral component of the analgesic effect of morphine as well as the synergistic interaction between central and peripheral mu receptors. The results of the reviewed studies convincingly show the key role of peripheral mu receptors in the development of tolerance to the analgesic effect of morphine after its systemic administration. The mechanisms of opioid tolerance also involve peripheral anti-opioid, pronociceptive systems such as NMDA receptors. It is well known that the same mechanisms are involved in maintaining peripheral hyperalgesia and allodynia. The development of analgesic drugs that act on peripheral antinociceptive systems offers a promising perspective on the possible treatment of acute and chronic pain.

scholarly journals Gating and Regulatory Mechanisms of TMEM16 Ion Channels and Scramblases

2021 ◽  
Vol 12 ◽  
Author(s):  
Son C. Le ◽  
Pengfei Liang ◽  
Augustus J. Lowry ◽  
Huanghe Yang
Keyword(s):  
Ion Channels ◽  
Molecular Mechanisms ◽  
Transmembrane Protein ◽  
Structural Features ◽  
Regulatory Mechanisms ◽  
Membrane Bilayer ◽  
Flip Flop ◽  
The Past ◽  
Activation Gating ◽  
Health And Disease

The transmembrane protein 16 (TMEM16) family consists of Ca2+-activated ion channels and Ca2+-activated phospholipid scramblases (CaPLSases) that passively flip-flop phospholipids between the two leaflets of the membrane bilayer. Owing to their diverse functions, TMEM16 proteins have been implicated in various human diseases, including asthma, cancer, bleeding disorders, muscular dystrophy, arthritis, epilepsy, dystonia, ataxia, and viral infection. To understand TMEM16 proteins in health and disease, it is critical to decipher their molecular mechanisms of activation gating and regulation. Structural, biophysical, and computational characterizations over the past decade have greatly advanced the molecular understanding of TMEM16 proteins. In this review, we summarize major structural features of the TMEM16 proteins with a focus on regulatory mechanisms and gating.

scholarly journals Electroacupuncture Relieves Visceral Hypersensitivity by Inactivating Protease-Activated Receptor 2 in a Rat Model of Postinfectious Irritable Bowel Syndrome

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Wanli Xu ◽  
Mengqian Yuan ◽  
Xiaoliang Wu ◽  
Hao Geng ◽  
Lu Chen ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Rat Model ◽  
Analgesic Effect ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Visceral Hypersensitivity ◽  
Mrna Levels ◽  
Irritable Bowel ◽  
Protease Activated Receptor 2 ◽  
Postinfectious Irritable Bowel Syndrome

Background. The role of protease-activated receptor 2 (PAR2) in the analgesic effect of electroacupuncture (EA) on visceral hypersensitivity (VH) in postinfectious irritable bowel syndrome (PI-IBS) has yet to be elucidated. Aim. In this study, we investigated the molecular mechanisms underlying the analgesic effect of EA in a rat model of PI-IBS. Methods. Visceral hypersensitivity was evaluated by the abdominal withdrawal reflex test before and after administration of the PAR2 agonist, PAR2-AP, and/or EA. The protein expression and mRNA levels of PAR2, CGRP, SP, and TPSP in colon tissues were measured by immunofluorescence, western blot, and RT-PCR. Results. We found that EA could alleviate VH and significantly decrease protein and mRNA levels of PAR2, TPSP, CGRP, and SP in PI-IBS rats. The analgesic effect of EA on VH was slightly reduced in the presence of PAR2-AP. Conclusions. These results suggest that EA alleviates VH symptoms through downregulation of the levels of the TPSP/PAR2/SP/CGRP signaling axis in colon tissues in PI-IBS rats. Together, our data suggests that PAR2 plays a critical role in the analgesic effect of EA on VH in PI-IBS.

scholarly journals The Pathophysiological Aspects of Cerebral Diseases

2022 ◽  
Author(s):  
Henrique Coelho Silva ◽  
Rafael Costa Lima Maia ◽  
Paulo Roberto Leitao de Vasconcelos ◽  
Orleancio Gomes Ripardo de Azevedo
Keyword(s):  
Oxidative Stress ◽  
Nervous Tissue ◽  
Molecular Mechanisms ◽  
Cerebrovascular Disorders ◽  
Neuron Specific Enolase ◽  
Cerebrovascular Diseases ◽  
Negative Effects ◽  
Cerebral Diseases ◽  
Negative Impacts ◽  
And Oxidative Stress

Introduction. Cerebrovascular disorders are the main causes of heavy burden health worldwide, also, it is critical to understand the pathophysiological mechanism and then trying to prevent the neurological sequels. Objective. To discuss the inflammatory and oxidative stress aspects associated to the cerebrovascular diseases, focusing on biomarkers, also the role of omega oils, and the intracellular molecular network associated to the tissue burden on those conditions. Results. One of the most promising biomarkers it is Neuron-Specific Enolase (NSE). Serum NSE levels were elevated in stroke-patients compared to the non-stroke controls. Also, studies have demonstrated that in specific ratio omega oils 3, 6 and 9 can ameliorate the inflammatory and oxidative stress in nervous tissue and could be useful to the inflammatory and oxidative stress negative effects of cerebrovascular diseases. In addition, the study of the molecular mechanisms is essential to understand which molecules could be addressed in cascade of events preventing the permanent damage on the nervous tissue. Final considerations. The studies on cerebrovascular disorders must precisely identify the mechanisms and key molecules involved and improve the time of diagnostics and prognostics reducing the negative impacts of those conditions.

Sign in / Sign up

Export Citation Format

Share Document