scholarly journals Effect of glucoraphanin and sulforaphane against chemotherapy-induced neuropathic pain: Kv7 potassium channels modulation by H2 S release in vivo

2018 ◽  
Vol 32 (11) ◽  
pp. 2226-2234 ◽  
Author(s):  
Elena Lucarini ◽  
Laura Micheli ◽  
Elena Trallori ◽  
Valentina Citi ◽  
Alma Martelli ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Potassium Channels

KCNN4 promotes the progression of lung adenocarcinoma by activating the AKT and ERK signaling pathways

2021 ◽  
pp. 1-15
Author(s):  
Ping Xu ◽  
Xiao Mo ◽  
Ruixue Xia ◽  
Long Jiang ◽  
Chengfei Zhang ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Lung Adenocarcinoma ◽  
Potassium Channel ◽  
Signaling Pathways ◽  
Epithelial To Mesenchymal Transition ◽  
Tumor Biology ◽  
Erk Signaling ◽  
Mesenchymal Transition

BACKGROUND: Potassium channels, encoded by more than seventy genes, are cell excitability transmembrane proteins and become evident to play essential roles in tumor biology. OBJECTIVE: The deregulation of potassium channel genes has been related to cancer development and patient prognosis. The objective of this study is to understand the role of potassium channels in lung cancer. METHODS: We examined all potassium channel genes and identified that KCNN4 is the most significantly overexpressed one in lung adenocarcinoma. The role and mechanism of KCNN4 in lung adenocarcinoma were further investigated by in vitro cell and molecular assay and in vivo mouse xenograft models. RESULTS: We revealed that the silencing of KCNN4 significantly inhibits cell proliferation, migration, invasion, and tumorigenicity of lung adenocarcinoma. Further studies showed that knockdown of KCNN4 promotes cell apoptosis, induces cell cycle arrested in the S phase, and is associated with the epithelial to mesenchymal transition (EMT) process. Most importantly, we demonstrated that KCNN4 regulates the progression of lung adenocarcinoma through P13K/AKT and MEK/ERK signaling pathways. The use of inhibitors that targeted AKT and ERK also significantly inhibit the proliferation and metastasis of lung adenocarcinoma cells. CONCLUSIONS: This study investigated the function and mechanism of KCNN4 in lung adenocarcinoma. On this basis, this means that KCNN4 can be used as a tumor marker for lung adenocarcinoma and is expected to become an important target for a potential drug.

Kir6.2-containing ATP-sensitive potassium channels protect cortical neurons from ischemic/anoxic injury in vitro and in vivo

Neuroscience ◽  
2007 ◽  
Vol 144 (4) ◽  
pp. 1509-1515 ◽  
Author(s):  
H.-S. Sun ◽  
Z.-P. Feng ◽  
P.A. Barber ◽  
A.M. Buchan ◽  
R.J. French
Keyword(s):  
Potassium Channels ◽  
Cortical Neurons ◽  
Anoxic Injury

scholarly journals Dexamethasone improves vascular hyporeactivity induced by LPS in vivo by modulating ATP-sensitive potassium channels activity

2003 ◽  
Vol 140 (1) ◽  
pp. 91-96 ◽  
Author(s):  
R D'Emmanuele Di Villa Bianca ◽  
L Lippolis ◽  
G Autore ◽  
A Popolo ◽  
S Marzocco ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Vascular Hyporeactivity

Direct and indirect pharmacological modulation of CCL2/CCR2 pathway results in attenuation of neuropathic pain — In vivo and in vitro evidence

2016 ◽  
Vol 297 ◽  
pp. 9-19 ◽  
Author(s):  
Anna Piotrowska ◽  
Klaudia Kwiatkowski ◽  
Ewelina Rojewska ◽  
Joanna Slusarczyk ◽  
Wioletta Makuch ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Pharmacological Modulation

scholarly journals Updating In Vivo and In Vitro Phosphorylation and Methylation Sites of Voltage-Gated Kv7.2 Potassium Channels

PROTEOMICS ◽  
2017 ◽  
Vol 17 (19) ◽  
pp. 1700015 ◽  
Author(s):  
Fatma Asli Erdem ◽  
Isabella Salzer ◽  
Seok Heo ◽  
Wei-Qiang Chen ◽  
Gangsoo Jung ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Voltage Gated

scholarly journals Identification of tetracycline combinations as EphB1 tyrosine kinase inhibitors for treatment of neuropathic pain

2021 ◽  
Vol 118 (10) ◽  
pp. e2016265118
Author(s):  
Mahmoud S. Ahmed ◽  
Ping Wang ◽  
Ngoc Uyen Nhi Nguyen ◽  
Yuji Nakada ◽  
Ivan Menendez-Montes ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Kinase Inhibitors ◽  
Catalytic Domain ◽  
Therapeutic Option ◽  
Atp Binding ◽  
Approved Drugs ◽  
Fda Approved Drugs

Previous studies have demonstrated that the synaptic EphB1 receptor tyrosine kinase is a major mediator of neuropathic pain, suggesting that targeting the activity of this receptor might be a viable therapeutic option. Therefore, we set out to determine if any FDA-approved drugs can act as inhibitors of the EphB1 intracellular catalytic domain. An in silico screen was first used to identify a number of tetracycline antibiotics which demonstrated potential docking to the ATP-binding catalytic domain of EphB1. Kinase assays showed that demeclocycline, chlortetracycline, and minocycline inhibit EphB1 kinase activity at low micromolar concentrations. In addition, we cocrystallized chlortetracycline and EphB1 receptor, which confirmed its binding to the ATP-binding domain. Finally, in vivo administration of the three-tetracycline combination inhibited the phosphorylation of EphB1 in the brain, spinal cord, and dorsal root ganglion (DRG) and effectively blocked neuropathic pain in mice. These results indicate that demeclocycline, chlortetracycline, and minocycline can be repurposed for treatment of neuropathic pain and potentially for other indications that would benefit from inhibition of EphB1 receptor kinase activity.

scholarly journals Locating the Site of Neuropathic Pain In Vivo Using MMP-12-Targeted Magnetic Nanoparticles

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Syeda Fabeha Husain ◽  
Raymond W. M. Lam ◽  
Tao Hu ◽  
Michael W. F. Ng ◽  
Z. Q. G. Liau ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Magnetic Resonance ◽  
Intrathecal Injection ◽  
Thermal Hyperalgesia ◽  
Spinal Nerve ◽  
Iron Oxide Nanoparticle ◽  
Anatomical Location ◽  
Spinal Nerves ◽  
Potential Biomarker

Neuropathic pain remains underrecognised and ineffectively treated in chronic pain sufferers. Consequently, their quality of life is considerably reduced, and substantial healthcare costs are incurred. The anatomical location of pain must be identified for definitive diagnosis, but current neuropsychological tools cannot do so. Matrix metalloproteinases (MMP) are thought to maintain peripheral neuroinflammation, and MMP-12 is elevated particularly in such pathological conditions. Magnetic resonance imaging (MRI) of the peripheral nervous system has made headway, owing to its high-contrast resolution and multiplanar features. We sought to improve MRI specificity of neural lesions, by constructing an MMP-12-targeted magnetic iron oxide nanoparticle (IONP). Its in vivo efficiency was evaluated in a rodent model of neuropathic pain, where the left lumbar 5 (L5) spinal nerve was tightly ligated. Spinal nerve ligation (SNL) successfully induced mechanical allodynia, and thermal hyperalgesia, in the left hind paw throughout the study duration. These neuropathy characteristics were absent in animals that underwent sham surgery. MMP-12 upregulation with concomitant macrophage infiltration, demyelination, and elastin fibre loss was observed at the site of ligation. This was not observed in spinal nerves contralateral and ipsilateral to the ligated spinal nerve or uninjured left L5 spinal nerves. The synthesised MMP-12-targeted magnetic IONP was stable and nontoxic in vitro. It was administered onto the left L5 spinal nerve by intrathecal injection, and decreased magnetic resonance (MR) signal was observed at the site of ligation. Histology analysis confirmed the presence of iron in ligated spinal nerves, whereas iron was not detected in uninjured left L5 spinal nerves. Therefore, MMP-12 is a potential biomarker of neuropathic pain. Its detection in vivo, using IONP-enhanced MRI, may be further developed as a tool for neuropathic pain diagnosis and management.

scholarly journals Suppression of Superficial Microglial Activation by Spinal Cord Stimulation Attenuates Neuropathic Pain Following Sciatic Nerve Injury in Rats

2020 ◽  
Vol 21 (7) ◽  
pp. 2390
Author(s):  
Masamichi Shinoda ◽  
Satoshi Fujita ◽  
Shiori Sugawara ◽  
Sayaka Asano ◽  
Ryo Koyama ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Electrical Stimulation ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Spinal Cord Stimulation ◽  
Microglial Activation ◽  
In Vivo Optical Imaging ◽  
Stimulation Of

We evaluated the mechanisms underlying the spinal cord stimulation (SCS)-induced analgesic effect on neuropathic pain following spared nerve injury (SNI). On day 3 after SNI, SCS was performed for 6 h by using electrodes paraspinally placed on the L4-S1 spinal cord. The effects of SCS and intraperitoneal minocycline administration on plantar mechanical sensitivity, microglial activation, and neuronal excitability in the L4 dorsal horn were assessed on day 3 after SNI. The somatosensory cortical responses to electrical stimulation of the hind paw on day 3 following SNI were examined by using in vivo optical imaging with a voltage-sensitive dye. On day 3 after SNI, plantar mechanical hypersensitivity and enhanced microglial activation were suppressed by minocycline or SCS, and L4 dorsal horn nociceptive neuronal hyperexcitability was suppressed by SCS. In vivo optical imaging also revealed that electrical stimulation of the hind paw-activated areas in the somatosensory cortex was decreased by SCS. The present findings suggest that SCS could suppress plantar SNI-induced neuropathic pain via inhibition of microglial activation in the L4 dorsal horn, which is involved in spinal neuronal hyperexcitability. SCS is likely to be a potential alternative and complementary medicine therapy to alleviate neuropathic pain following nerve injury.

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