Effects of miR-338 on morphine tolerance by targeting CXCR4 in a rat model of bone cancer pain

The present study aimed to investigate the effects of miR-338 on morphine tolerance through the targeting of CXC chemokine receptor-4 (CXCR4) in a rat model of bone cancer pain (BCP). Sprague–Dawley (SD) rats were obtained and divided into model saline (n=10), model morphine (n=50), normal saline (n=10) and normal morphine (healthy rats, n=10) groups. After BCP rat model establishment, the remaining SD rats (n=40) in the model saline group were assigned into pLV-THM-miR-338, pLV-THM-anti-miR-338, CXCR4 shRNA, blank and PBS groups. Luciferase reporter gene assay was used for luciferase activity. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to detect the miR-338 and CXCR4 mRNA and protein expression. The model saline group showed increased mRNA and protein expressions of CXCR4 but decreased miR-338 compared with the model saline group, and the model morphine group had increased mRNA and protein expressions of CXCR4 but decreased miR-338 compared with the model saline group. The mRNA and protein expressions of miR-338 in the pLV-THM-miR-338 group increased remarkably while those of the pLV-THM-anti-miR-338 group decreased significantly compared with the CXCR4 shRNA, blank and PBS groups. The pLV-THM-miR-338, pLV-THM-anti-miR-338, CXCR4 shRNA and CXCR4 mRNA groups all had lower mRNA and protein expressions of CXCR4 than those in the blank and PBS groups. miR-338 exerts significant influence in the inhibition of morphine tolerance by suppressing CXCR4 in BCP.

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Activation of spinal microglia and astrocytes in a rat model of bone cancer pain

Neuroscience Research ◽

10.1016/j.neures.2009.09.947 ◽

2009 ◽

Vol 65 ◽

pp. S178

Author(s):

Yan-Qing Wang ◽

Qi-Liang Mao-Ying ◽

Xiao-Wei Wang ◽

Gen-Cheng Wu

Keyword(s):

Cancer Pain ◽

Rat Model ◽

Bone Cancer ◽

Bone Cancer Pain

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Protease-Activated Receptor 2 Antagonist Potentiates Analgesic Effects of Systemic Morphine in a Rat Model of Bone Cancer Pain

Regional Anesthesia and Pain Medicine ◽

10.1097/aap.0000000000000211 ◽

2015 ◽

Vol 40 (2) ◽

pp. 158-165 ◽

Cited By ~ 5

Author(s):

Yanju Bao ◽

Wei Hou ◽

Liping Yang ◽

Xiangying Kong ◽

Maobo Du ◽

...

Keyword(s):

Cancer Pain ◽

Rat Model ◽

Bone Cancer ◽

Bone Cancer Pain ◽

Analgesic Effects ◽

Protease Activated Receptor 2

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circStrn3 is involved in bone cancer pain regulation in a rat model

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmaa018 ◽

2020 ◽

Vol 52 (5) ◽

pp. 495-505

Author(s):

Yiwen Zhang ◽

Xiaoxia Zhang ◽

Zumin Xing ◽

Shuyi Tang ◽

Hanwen Chen ◽

...

Keyword(s):

Cancer Pain ◽

Rat Model ◽

Molecular Mechanisms ◽

Bone Cancer ◽

Test Body ◽

Differentially Expressed ◽

Bone Cancer Pain ◽

Biological Regulation ◽

Cellular Processes ◽

Simplex Infection

Abstract Bone cancer pain (BCP) is a common chronic pain that is caused by a primary or metastatic bone tumor. More detailed molecular mechanisms of BCP are warranted. In this study, we established a BCP rat model. The von Frey hair test, body weight, and hematoxylin and eosin staining were employed. We screened differentially expressed circRNAs (DECs) between the BCP group and sham group. The results revealed that 850 DECs were significantly up-regulated and 644 DECs were significantly down-regulated in the BCP group. Furthermore, we identified 1177 differentially expressed genes (DEGs) significantly up-regulated and 565 DEGs significantly down-regulated in the BCP group. Gene Ontology annotation of all 1742 DEGs revealed that biological regulation of metabolic processes, cellular processes, and binding were the top enriched terms. For Kyoto Encyclopedia of Genes and Genomes analysis, phagosome, HTLV-I infection, proteoglycans in cancer, and herpes simplex infection were significantly enriched in this study. In addition, we identified four selected circRNAs, chr6:72418120|72430205, chr20:7561057|7573740, chr18:69943105|69944476, and chr5:167516581|167558250, by quantitative real time PCR. chr6:72418120|72430205 (circStrn3) was selected for further study based on expression level and the circRNA–miRNA–mRNA network table. Western blot analysis suggested that knockdown of circStrn3 could effectively induce Walker 256 cell apoptosis. In summary, our study provided a more in-depth understanding of the molecular mechanisms of BCP.

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Antinociceptive Effect of Intrathecal Injection of Genetically Engineered Human Bone Marrow Stem Cells Expressing the Human Proenkephalin Gene in a Rat Model of Bone Cancer Pain

Pain Research and Management ◽

10.1155/2017/7346103 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Yi Sun ◽

Yuke Tian ◽

Haifeng Li ◽

Dengwen Zhang ◽

Qiang Sun

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Gene Transfer ◽

Cancer Pain ◽

Rat Model ◽

Bone Cancer ◽

Genetically Engineered ◽

Human Bone ◽

Human Bone Marrow ◽

Bone Cancer Pain

Background. This study aimed to investigate the use of human bone marrow mesenchymal stem cells (hBMSCs) genetically engineered with the human proenkephalin (hPPE) gene to treat bone cancer pain (BCP) in a rat model.Methods. Primary cultured hBMSCs were passaged and modified with hPPE, and the cell suspensions (6 × 106) were then intrathecally injected into a rat model of BCP. Paw mechanical withdrawal threshold (PMWT) was measured before and after BCP. The effects of hPPE gene transfer on hBMSC bioactivity were analyzed in vitro and in vivo.Results. No changes were observed in the surface phenotypes and differentiation of hBMSCs after gene transfer. The hPPE-hBMSC group showed improved PMWT values on the ipsilateral side of rats with BCP from day 12 postoperatively, and the analgesic effect was reversed by naloxone. The levels of proinflammatory cytokines such as IL-1βand IL-6 were ameliorated, and leucine-enkephalin (L-EK) secretion was augmented, in the hPPE-engineered hBMSC group.Conclusion. The intrathecal administration of BMSCs modified with the hPPE gene can effectively relieve pain caused by bone cancer in rats and might be a potentially therapeutic tool for cancer-related pain in humans.

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Spinal glial activation in a new rat model of bone cancer pain produced by prostate cancer cell inoculation of the tibia

Pain ◽

10.1016/j.pain.2005.08.001 ◽

2005 ◽

Vol 118 (1) ◽

pp. 125-136 ◽

Cited By ~ 138

Author(s):

Rui-Xin Zhang ◽

Bing Liu ◽

Linbo Wang ◽

Ke Ren ◽

Jian-Tian Qiao ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Pain ◽

Cancer Cell ◽

Rat Model ◽

Prostate Cancer Cell ◽

Bone Cancer ◽

Glial Activation ◽

Bone Cancer Pain ◽

Cell Inoculation

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Behavioral, Medical Imaging and Histopathological Features of a New Rat Model of Bone Cancer Pain

PLoS ONE ◽

10.1371/journal.pone.0013774 ◽

2010 ◽

Vol 5 (10) ◽

pp. e13774 ◽

Cited By ~ 35

Author(s):

Louis Doré-Savard ◽

Valérie Otis ◽

Karine Belleville ◽

Myriam Lemire ◽

Mélanie Archambault ◽

...

Keyword(s):

Medical Imaging ◽

Cancer Pain ◽

Rat Model ◽

Bone Cancer ◽

Bone Cancer Pain ◽

Histopathological Features

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Preconditioning with hydrogen sulfide prevents bone cancer pain in rats through a proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway

Experimental Biology and Medicine ◽

10.1177/1535370217740859 ◽

2017 ◽

Vol 243 (1) ◽

pp. 57-65 ◽

Cited By ~ 3

Author(s):

Li Zhuang ◽

Ke Li ◽

Gaowei Wang ◽

Tao Shou ◽

Chunlin Gao ◽

...

Keyword(s):

Spinal Cord ◽

Cancer Pain ◽

Rat Model ◽

Mechanical Allodynia ◽

Antinociceptive Effect ◽

Thermal Hyperalgesia ◽

Bone Cancer ◽

Bone Cancer Pain ◽

Kinase Pathway

Bone cancer pain (BCP) is a severe type of hyperpathic pain occurring with primary bone tumors or advanced cancers which metastasize to bones. BCP can detrimentally reduce quality of life and presents a challenge to modern medicine. Studies have shown that exogenous H2S may act as a neuroprotectant to protect against some diseases in central nervous system. The preset study aimed to investigate the antinociceptive effect of H2S in BCP. We first measured the changes of serum H2S in patients with BCP and analyzed the relationship between them, then investigated the effect of H2S preconditioning on BCP, and explored the mechanism in rat model. Our results revealed that serum H2S level was negatively correlated with pain scores. In the rat model of BCP, preconditioning with H2S significantly reduced BCP, demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia. The mechanism of H2S preconditioning may involve microglia deactivation and inflammation inhibition in the spinal cord, in which the proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway is activated. Impact statement Bone cancer pain (BCP) significantly decreases the life quality of patients or their life expectancy and causes a severe health burden to the society. However, as the exact mechanism of BCP is still poorly understood, no effective treatment has been developed yet. There are some pain medicines now, but they have some inevitable side effects. Additional therapeutic strategies are urgently needed. First, we revealed that preconditioning with H2S significantly reduced BCP, demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia. Second, the mechanism of H2S preconditioning was elucidated. It may involve microglia deactivation and inflammation inhibition in the spinal cord, in which the proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway is activated. This novel finding may significantly help us to understand the difference between the roles of endogenous H2S and exogenous H2S in the development of BCP and present us a new strategy of pain management.

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Effects of Electroacupuncture Treatment on Bone Cancer Pain Model with Morphine Tolerance

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/8028474 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 3

Author(s):

Lei Sima ◽

Bifa Fan ◽

Longtao Yan ◽

Yuan Shui

Keyword(s):

Dorsal Root ◽

Early Stage ◽

Bone Cancer ◽

Morphine Tolerance ◽

Bone Cancer Pain ◽

Pain Model ◽

Analgesic Effects ◽

Sd Rats ◽

Calcitonin Gene ◽

Electroacupuncture Treatment

Objective. To explore the efficacy of electroacupuncture treatment in cancer induced bone pain (CIBP) rat model with morphine tolerance and explore changes of calcitonin-gene related peptide (CGRP) expression in dorsal root ganglion (DRG).Methods. Forty SD rats were divided into five groups: sham, CIBP (B), CIBP + morphine (BM), CIBP + electroacupuncture (BE), and CIBP + morphine + electroacupuncture (BME). B, BM, BE, and BME groups were prepared CIBP model. The latter three groups then accepted morphine, electroacupuncture, and morphine combined electroacupuncture, separately, nine days consecutively (M1 to M9). Mechanical withdraw threshold (MWT) was evaluated.Results. BE group only had differences in M1, M2, and M3 compared to B group (P<0.01). From M5, BM group showed significantly decreased MWT. Electroacupuncture could obtain analgesic effects only at early stage (M1 to M5). From M5 to M9, BME had the differences with BM group (P<0.01). IOD value of CGRP in BM and BME was substantially less than in B group. CGRP in BME was significantly lower than that in BM group (P<0.01).Conclusion. When used in combination with electroacupuncture, morphine could result in improving analgesic effects and reducing tolerance. CGRP may be associated with pain behaviors.

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