scholarly journals Electroacupuncture Reduces the Effects of Acute Noxious Stimulation on the Electrical Activity of Pain-Related Neurons in the Hippocampus of Control and Neuropathic Pain Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Jun-Ying Wang ◽  
Renbo Chen ◽  
Shu-Ping Chen ◽  
Yong-Hui Gao ◽  
Jian-Liang Zhang ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Electrical Activity ◽  
Nerve Stimulation ◽  
Mek Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Noxious Stimulation ◽  
Ca1 Region ◽  
Mitogen Activated Protein ◽  
Hippocampal Area ◽  
Sciatic Nerve Stimulation

To study the effects of acupuncture analgesia on the hippocampus, we observed the effects of electroacupuncture (EA) and mitogen-activated protein kinase (MEK) inhibitor on pain-excited neurons (PENs) and pain-inhibited neurons (PINs) in the hippocampal area CA1 of sham or chronic constrictive injury (CCI) rats. The animals were randomly divided into a control, a CCI, and a U0126 (MEK1/2 inhibitor) group. In all experiments, we briefly (10-second duration) stimulated the sciatic nerve electrically and recorded the firing rates of PENs and PINs. The results showed that in both sham and CCI rats brief sciatic nerve stimulation significantly increased the electrical activity of PENs and markedly decreased the electrical activity of PINs. These effects were significantly greater in CCI rats compared to sham rats. EA treatment reduced the effects of the noxious stimulus on PENs and PINs in both sham and CCI rats. The effects of EA treatment could be inhibited by U0126 in sham-operated rats. The results suggest that EA reduces effects of acute sciatic nerve stimulation on PENs and PINs in the CA1 region of the hippocampus of both sham and CCI rats and that the ERK (extracellular regulated kinase) signaling pathway is involved in the modulation of EA analgesia.

scholarly journals An investigation of arterial insufficiency in the rat hindlimb Correlation of skeletal muscle bloodflow and glucose utilization in vivo

1986 ◽  
Vol 240 (2) ◽  
pp. 395-401 ◽  
Author(s):  
R A Challiss ◽  
D J Hayes ◽  
G K Radda
Keyword(s):  
Skeletal Muscle ◽  
Sciatic Nerve ◽  
Glucose Uptake ◽  
Nerve Stimulation ◽  
Linear Correlation ◽  
Glucose Utilization ◽  
Fold Increase ◽  
Artery Ligation ◽  
Sciatic Nerve Stimulation

Muscle bloodflow and the rate of glucose uptake and phosphorylation were measured in vivo in rats 7 days after unilateral femoral artery ligation and section. Bloodflow was determined by using radiolabelled microspheres. At rest, bloodflow to the gastrocnemius, plantaris and soleus muscles of the ligated limb was similar to their respective mean contralateral control values; however, bilateral sciatic nerve stimulation at 1 Hz caused a less pronounced hyperaemic response in the muscles of the ligated limb, being 59, 63 and 49% of their mean control values in the gastrocnemius, plantaris and soleus muscles respectively. The rate of glucose utilization was determined by using the 2-deoxy[3H]glucose method [Ferré, Leturque, Burnol, Penicaud & Girard (1985) Biochem. J. 228, 103-110]. At rest, the rate of glucose uptake and phosphorylation was statistically significantly increased in the gastrocnemius and soleus muscles of the ligated limb, being 126 and 140% of the mean control values respectively. Bilateral sciatic nerve stimulation at 1 Hz caused a 3-5-fold increase in the rate of glucose utilization by the ligated and contralateral control limbs; furthermore, the rate of glucose utilization was significantly increased in the muscles of the ligated limb, being 140, 129 and 207% of their mean control values respectively. For the range of bloodflow to normally perfused skeletal muscle at rest or during isometric contraction determined in the present study, a linear correlation between the rate of glucose utilization and bloodflow can be demonstrated. Applying similar methods of regression analysis to glucose utilization and bloodflow to muscles of the ligated limb reveals a similar linear correlation. However, the rate of glucose utilization at a given bloodflow is increased in muscles of the ligated limb, indicating an adaptation of skeletal muscle to hypoperfusion.

scholarly journals Role of Mitogen-Activated Protein Kinase Pathway in Prostaglandin F2α-Induced Rat Puerperal Uterine Contraction

Endocrinology ◽  
1997 ◽  
Vol 138 (8) ◽  
pp. 3103-3111 ◽  
Author(s):  
Masahide Ohmichi ◽  
Koji Koike ◽  
Akiko Kimura ◽  
Kanji Masuhara ◽  
Hiromasa Ikegami ◽  
...  
Keyword(s):  
Map Kinase ◽  
Uterine Contraction ◽  
Prostaglandin F2α ◽  
Mek Inhibitor ◽  
Biological Action ◽  
Mitogen Activated Protein Kinase ◽  
Myometrial Cells ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

Abstract In this study, prostaglandin (PG) F2α was found to activate mitogen-activated protein (MAP) kinase and MAP kinase kinase (MEK) in cultured rat puerperal uterine myometrial cells. PGF2α stimulation also led to an increase in phosphorylation of raf-1, son of sevenless (SOS), and Shc. Furthermore, we examined the mechanism by which PGF2α induced MAP kinase phosphorylation. Both pertussis toxin (10 ng/ml), which inactivates Gi/Go proteins, and expression of a peptide derived from the carboxyl terminus of the β-adrenergic receptor kinase 1 (βARK1), which specifically blocks signaling mediated by the βγ subunits of G proteins, blocked the PGF2α-induced activation of MAP kinase. Ritodrine (1 μm), which is known to relax uterine muscle contraction, attenuated PGF2α-induced tyrosine phosphorylation of MAP kinase. Moreover, to examine the role of MAP kinase pathway in uterine contraction, an inhibitor of MEK activity, PD098059, was used. Although MEK inhibitor had no effect on PGF2α-induced calcium mobilization, this inhibitor partially inhibited PGF2α-induced uterine contraction. These results provide evidence that PGF2α stimulates the MAP kinase signaling pathway in cultured rat puerperal uterine myometrial cells through Gβγ protein, suggesting that this new pathway may play an important role in the biological action of PGF2α on these cells.

Clinical efficacy with dabrafenib and trametinib in a T599_V600insT poorly differentiated metastatic thyroid carcinoma

2021 ◽  
Vol 14 (8) ◽  
pp. e243264
Author(s):  
Chung-Shien Lee ◽  
Emily Miao ◽  
Kasturi Das ◽  
Nagashree Seetharamu
Keyword(s):  
Thyroid Carcinoma ◽  
Kinase Inhibitors ◽  
Mek Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Braf Mutations ◽  
Effective Treatment Option ◽  
Mitogen Activated Protein ◽  
Treatment Data ◽  
Poorly Differentiated

BRAF (v-raf murine sarcoma viral oncogene homolog B1) and MEK (mitogen-activated protein kinase kinase) inhibitors have been shown to improve clinical outcomes in tumours presenting with mutations in the BRAF gene. The most common form of BRAF mutation is V600E/K and has been shown to occur in thyroid cancers. Treatment data for patients harbouring less frequent BRAF mutations are limited. In vitro studies have shown that mutations in codons 599–601 increase kinase activity similar to that in V600E mutations, which suggests that BRAF and MEK inhibitors could be an effective treatment option. Here, we report a case of a patient with thyroid carcinoma harbouring a rare amino acid insertion in codon 599 of the BRAF gene (T599_V600insT) treated with a BRAF and MEK inhibitor.

scholarly journals Computational Study on the Effect of Inactivating/Activating Mutations on the Inhibition of MEK1 by Trametinib

2020 ◽  
Vol 21 (6) ◽  
pp. 2167
Author(s):  
Jingxuan Zhu ◽  
Congcong Li ◽  
Hengzheng Yang ◽  
Xiaoqing Guo ◽  
Tianci Huang ◽  
...  
Keyword(s):  
Molecular Dynamic ◽  
Conformational Changes ◽  
Computational Study ◽  
Md Simulations ◽  
Mek Inhibitor ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Lung Cancers ◽  
Mitogen Activated Protein ◽  
Alk Positive

Activation of the mitogen-activated protein kinase (MAPK) signaling pathway regulated by human MAP kinase 1 (MEK1) is associated with the carcinogenesis and progression of numerous cancers. In addition, two active mutations (P124S and E203K) have been reported to enhance the activity of MEK1, thereby eventually leading to the tumorigenesis of cancer. Trametinib is an MEK1 inhibitor for treating EML4-ALK-positive, EGFR-activated, and KRAS-mutant lung cancers. Therefore, in this study, molecular docking and molecular dynamic (MD) simulations were performed to explore the effects of inactive/active mutations (A52V/P124S and E203K) on the conformational changes of MEK1 and the changes in the interaction of MEK1 with trametinib. Moreover, steered molecular dynamic (SMD) simulations were further utilized to compare the dissociation processes of trametinib from the wild-type (WT) MEK1 and two active mutants (P124S and E203K). As a result, trametinib had stronger interactions with the non-active MEK1 (WT and A52V mutant) than the two active mutants (P124S and E203K). Moreover, two active mutants may make the allosteric channel of MEK1 wider and shorter than that of the non-active types (WT and A52V mutant). Hence, trametinib could dissociate from the active mutants (P124S and E203K) more easily compared with the WT MEK1. In summary, our theoretical results demonstrated that the active mutations may attenuate the inhibitory effects of MEK inhibitor (trametinib) on MEK1, which could be crucial clues for future anti-cancer treatment.

scholarly journals Sciatic nerve stimulation activates the retrotrapezoid nucleus in anesthetized rats

2016 ◽  
Vol 116 (5) ◽  
pp. 2081-2092 ◽  
Author(s):  
Roy Kanbar ◽  
Ruth L. Stornetta ◽  
Patrice G. Guyenet
Keyword(s):  
Sciatic Nerve ◽  
Nerve Stimulation ◽  
Motor Nucleus ◽  
Sprague Dawley ◽  
Neuron Firing ◽  
Afferent Stimulation ◽  
Retrotrapezoid Nucleus ◽  
Facial Motor Nucleus ◽  
Stimulation Experiments ◽  
Sciatic Nerve Stimulation

Retrotrapezoid nucleus (RTN) neurons sustain breathing automaticity. These neurons have chemoreceptor properties, but their firing is also regulated by multiple synaptic inputs of uncertain function. Here we test whether RTN neurons, like neighboring presympathetic neurons, are excited by somatic afferent stimulation. Experiments were performed in Inactin-anesthetized, bilaterally vagotomized, paralyzed, mechanically ventilated Sprague-Dawley rats. End-expiratory CO2 (eeCO2) was varied between 4% and 10% to modify rate and amplitude of phrenic nerve discharge (PND). RTN and presympathetic neurons were recorded extracellularly below the facial motor nucleus with established criteria. Sciatic nerve stimulation (SNstim, 1 ms, 0.5 Hz) slightly increased blood pressure (6.6 ± 1.6 mmHg) and heart rate and, at low eeCO2 (<5.5%), entrained PND. Ipsi- and contralateral SNstim produced the known biphasic activation of presympathetic neurons. SNstim evoked a similar but weaker biphasic response in up to 67% of RTN neurons and monophasic excitation in the rest. At low eeCO2, RTN neurons were silent and responded more weakly to SNstim than at high eeCO2. RTN neuron firing was respiratory modulated to various degrees. The phasic activation of RTN neurons elicited by SNstim was virtually unchanged at high eeCO2 when PND entrainment to the stimulus was disrupted. Thus RTN neuron response to SNstim did not result from entrainment to the central pattern generator. Overall, SNstim shifted the relationship between RTN firing and eeCO2 upward. In conclusion, somatic afferent stimulation increases RTN neuron firing probability without altering their response to CO2. This pathway may contribute to the hyperpnea triggered by nociception, exercise (muscle metabotropic reflex), or hyperthermia.

COMPLETE INHIBITION OF ADRENOCORTICAL RESPONSES FOLLOWING SCIATIC NERVE STIMULATION IN RATS WITH HYPOTHALAMIC ISLANDS

1975 ◽  
Vol 78 (3) ◽  
pp. 539-544 ◽  
Author(s):  
Shaul Feldman ◽  
Nisim Conforti ◽  
Israel Chowers
Keyword(s):  
Sciatic Nerve ◽  
Nerve Stimulation ◽  
Acoustic Stimulation ◽  
Plasma Corticosterone ◽  
Neural Pathways ◽  
Implanted Electrodes ◽  
Sciatic Nerve Stimulation ◽  
Adrenocortical Responses ◽  
Pentobarbital Anaesthesia ◽  
Intact Rats

ABSTRACT Previous studies from this laboratory have demonstrated that in rats with hypothalamic islands the adrenocortical response to photic and acoustic stimulation was partially inhibited indicating that they were at least to a certain degree neurally mediated, though ether stress produced normal adrenocortical responses. With the purpose of determining to what extent afferent somatosensory connections to the hypothalamus participate in the activation of adrenocortical responses following sciatic nerve stimulation, the effects of this stimulus applied through chronically implanted electrodes were studied on the plasma corticosterone levels in pentobarbital anaesthetized intact animals and in rats with hypothalamic islands. Ether stress or sciatic nerve stimulation for 2 min in intact rats produced a rise of plasma corticosterone to 32.1 ± 1.2 and 32.1 ± 1.8 μg/100 ml, respectively. However, in animals with hypothalamic islands the corresponding values were 29.2 ± 1.8 and 12.4 ± 0.8 μg/100 ml, respectively. The latter value was not significantly different from the basal corticosterone levels (13.0 ± 1.2 μg/100 ml) found in rats 15 min after pentobarbital anaesthesia, the time when the sciatic stimulus was applied. The present data indicate that the adrenocortical discharge following sciatic nerve stimulation is completely inhibited by hypothalamic deafferentation and therefore depends entirely on the activation of the afferent neural pathways to the hypothalamus.

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