scholarly journals Yokukansan Alleviates Cancer Pain by Suppressing Matrix Metalloproteinase-9 in a Mouse Bone Metastasis Model

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Kenta Nakao ◽  
Atsushi Fujiwara ◽  
Nobuyasu Komasawa ◽  
Denan Jin ◽  
Manabu Kitano ◽  
...  
Keyword(s):  
Bone Metastasis ◽  
Matrix Metalloproteinase ◽  
Cancer Pain ◽  
Weight Bearing ◽  
Intraperitoneal Administration ◽  
Herbal Medicines ◽  
Bone Cancer ◽  
Pain Behavior ◽  
Bone Cancer Pain ◽  
Metastasis Model

Bone cancer pain control is difficult because it includes various characteristics of pain such as nociceptic and neuropathic pain. In this study, we investigated the effect of yokukansan (YKS), one of the traditional Japanese herbal medicines, on cancer pain in mouse bone metastasis model. Oral administration of YKS significantly alleviated pain behavior measured by quantitative body weight bearing. Furthermore, the pain behavior was also significantly alleviated by intrathecal and intraperitoneal administration of matrix metalloproteinase- (MMP-) 9 inhibitor, but not of MMP-2 inhibitor. MMP-9 expression was significantly elevated in the bone tissue on day 3 after carcinoma cell injection and in the ipsilateral spinal cord on day 7, which was suppressed by YKS administration. Taken together, these results suggest that YKS alleviates cancer pain via suppressing MMP-9 expression in bone metastasis model in mice.

Analgesic effects of neurotensin agonists in a rat bone cancer pain model

2016 ◽  
Author(s):  
Louis Dore-Savard ◽  
Pascal Tetreault ◽  
Melisange Roux ◽  
Marylie Martel ◽  
Myriam Lemire ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Weight Bearing ◽  
Bone Cancer ◽  
Opioid Analgesics ◽  
Bone Cancer Pain ◽  
Intractable Pain ◽  
Analgesic Effects ◽  
Selective Agonist ◽  
Neurotensin Receptors ◽  
Pain Models

Bone metastases are a source of intractable pain, resistant to conventional opioid and non-opioid analgesics. The neurotensin system represents a potential pathway toward bone cancer pain (BCP) relieve via the inhibition of its receptors NTS1 and NTS2. Capitalizing on our recent results using neurotensin analogs in inflammatory and neuropathic pain models, we here show, for the first time, a potential role for neurotensin receptors agonists in the treatment of BCP. The novel non-selective agonist JMV-2009 (300 μg/kg) reversed mechanical allodynia in our rodent BCP model at both early and late stages of the disease. The NTS2-selective agonist JMV-431 (90 μg/kg), in addition to anti-allodynia, also had an effect on weight bearing deficits. In parallel, we tested proven analgesics from several classes to put the effect of neurotensin analogs in perspective and found that morphine (3 mg/kg), tramadol (15 mg/kg) and amitriptyline (10 mg/kg) had mild effects on BCP while the cannabinoid nabilone (1 mg/kg) significantly reversed both allodynia and weight bearing deficits. Taken together, our results affirm the potential of the modulation of the neurotensin system for the development of new analgesics for the treatment of bone cancer pain.

Bone cancer pain model in mice: evaluation of pain behavior, bone destruction and morphine sensitivity

2004 ◽  
Vol 79 (2) ◽  
pp. 243-251 ◽  
Author(s):  
Hilde Vermeirsch ◽  
Rony M. Nuydens ◽  
Philip L. Salmon ◽  
Theo F. Meert
Keyword(s):  
Cancer Pain ◽  
Bone Destruction ◽  
Bone Cancer ◽  
Pain Behavior ◽  
Bone Cancer Pain ◽  
Pain Model

scholarly journals The circular RNA circSlc7a11 promotes bone cancer pain pathogenesis in rats by modulating LLC-WRC 256 cell proliferation and apoptosis

2021 ◽  
Author(s):  
Han-Wen Chen ◽  
Xiao-Xia Zhang ◽  
Zhu-Ding Peng ◽  
Zu-Min Xing ◽  
Yi-Wen Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Pain ◽  
Expression Profiles ◽  
Bone Cancer ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Bone Cancer Pain ◽  
Circular Rnas ◽  
Altered Expression ◽  
Proliferation And Apoptosis

AbstractTreatment of bone cancer pain (BCP) caused by bone metastasis in advanced cancers remains a challenge in clinical oncology, and the underlying mechanisms of BCP are poorly understood. This study aimed to investigate the pathogenic roles of circular RNAs (circRNAs) in regulating cancer cell proliferation and BCP development. Eight differentially expressed circRNAs in the rat spinal cord were validated by agarose gel electrophoresis and Sanger sequencing. Expression of circRNAs and mRNAs was detected by quantitative RT-PCR. MTS assay and flow cytometry were performed to analyze cell proliferation and apoptosis, respectively. Differentially expressed mRNA profiles were characterized by deep RNA sequencing, hierarchical clustering, and functional categorization. The interactions among circRNAs, microRNAs (miRNAs), and mRNAs were predicted using TargetScan. Additionally, western blot was performed to determine the protein levels of Pax8, Isg15, and Cxcl10. Multiple circRNAs were differentially expressed in the spinal cords of BCP model rats; of these, circSlc7a11 showed the greatest increase in expression. The overexpression of circSlc7a11 significantly promoted cell proliferation and repressed apoptosis of LLC-WRC 256 and UMR-106 cells, whereas circSlc7a11 silencing produced the opposite effects. Altered expression of circSlc7a11 also induced substantial changes in the mRNA expression profiles of LLC-WRC 256 cells; these changes were linked to multiple apoptotic processes and signaling pathways, such as the chemokine signaling pathway, and formed a complex circRNA/miRNA/mRNA network. Additionally, Pax8, Isg15, and Cxc110 protein level in LLC-WRC 256 cells was consistent with the mRNA results. The circRNA circSlc7a11 regulates rat BCP development by modulating LLC-WRC 256 cell proliferation and apoptosis through multiple-signaling mechanisms.

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