scholarly journals Topical Treatment with Xiaozheng Zhitong Paste (XZP) Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Yanju Bao ◽  
Yebo Gao ◽  
Maobo Du ◽  
Wei Hou ◽  
Liping Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Pain ◽  
Structural Damage ◽  
Bone Pain ◽  
Bone Destruction ◽  
Bone Cancer ◽  
Bone Cancer Pain ◽  
Osteoblast Activity ◽  
Mechanical Threshold ◽  
Bone Damage

To explore the effects and mechanisms of Xiaozheng Zhitong Paste (XZP) on bone cancer pain, Wistar rats were inoculated with vehicle or prostate cancer PC-3 into the tibia bone and treated topically with inert paste, XZP at 15.75, 31.5, or 63 g/kg twice per day for 21 days. Their bone structural damage, nociceptive behaviors, bone osteoclast and osteoblast activity, and the levels of OPG, RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-αwere examined. In comparison with that in the placebo group, significantly reduced numbers of invaded cancer cells, decreased levels of bone damage and mechanical threshold and paw withdrawal latency, lower levels of serum TRACP5b, ICTP, PINP, and BAP, and less levels of bone osteoblast and osteoclast activity were detected in the XZP-treated rats (P<0.05). Moreover, significantly increased levels of bone OPG but significantly decreased levels of RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-αwere detected in the XZP-treated rats (P<0.05for all). Together, XZP treatment significantly mitigated the cancer-induced bone damage and bone osteoclast and osteoblast activity and alleviated prostate cancer-induced bone pain by modulating the RANKL/RANK/OPG pathway and bone cancer-related inflammation in rats.

scholarly journals Endoplasmic Reticulum Stress Contributes to Nociception via Neuroinflammation in a Murine Bone Cancer Pain Model

2020 ◽  
Vol 132 (2) ◽  
pp. 357-372 ◽  
Author(s):  
Yanting Mao ◽  
Chenchen Wang ◽  
Xinyu Tian ◽  
Yulin Huang ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cancer Pain ◽  
Inflammatory Mediators ◽  
Bone Cancer ◽  
Intrathecal Administration ◽  
Bone Cancer Pain ◽  
Stress Markers ◽  
Mechanical Threshold ◽  
Tnf Α

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Prolonged endoplasmic reticulum stress has been identified in various diseases. Inflammatory mediators, which have been shown to induce endoplasmic reticulum stress in several studies, have been suggested to serve as the important modulators in pain development. In this study, the authors hypothesized that the endoplasmic reticulum stress triggered by inflammatory mediators contributed to pain development. Methods The authors used a male mouse model of bone cancer pain. The control mice were intrathecally injected with tumor necrosis factor-α (TNF-α) and lipopolysaccharide, the bone cancer pain mice were intrathecally injected with the endoplasmic reticulum stress inhibitors 4-PBA and GSK2606414. The nociceptive behaviors, endoplasmic reticulum stress markers, and inflammatory mediators were assessed. Results Increased expression of the p-RNA-dependent protein kinase-like endoplasmic reticulum kinase and p-eukaryotic initiation factor 2α were found in the spinal neurons during bone cancer pain, along with upregulation of inflammatory mediators (TNF-α, interleukin 1β, and interleukin 6). Intrathecal administration of TNF-α or lipopolysaccharide increased the expression of endoplasmic reticulum stress markers in control mice. Inhibition of endoplasmic reticulum stress by intrathecal administration of 4-PBA (baseline vs. 3 h: 0.34 ± 0.16 g vs. 1.65 ± 0.40 g in paw withdrawal mechanical threshold, 8.00 ± 1.20 times per 2 min vs. 0.88 ± 0.64 times per 2 min in number of spontaneous flinches, P &lt; 0.001, n = 8) or GSK2606414 (baseline vs. 3 h: 0.37 ± 0.08 g vs. 1.38 ± 0.11 g in paw withdrawal mechanical threshold, 8.00 ± 0.93 times per 2 min vs. 3.25 ± 1.04 times per 2 min in number of spontaneous flinches, P &lt; 0.001, n = 8) showed time- and dose-dependent antinociception. Meanwhile, decreased expression of inflammatory mediators (TNF-α, interleukin 1β, and interleukin 6), as well as decreased activation of astrocytes in the spinal cord, were found after 4-PBA or GSK2606414 treatment. Conclusions Inhibition of inflammatory mediator–triggered endoplasmic reticulum stress in spinal neurons attenuates bone cancer pain via modulation of neuroinflammation, which suggests new approaches to pain relief.

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

Pain ◽  
2005 ◽  
Vol 118 (1) ◽  
pp. 125-136 ◽  
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

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 Phosphoproteomic Profiling of Rat’s Dorsal Root Ganglia Reveals mTOR as a Potential Target in Bone Cancer Pain and Electro-Acupuncture’s Analgesia

2021 ◽  
Vol 12 ◽  
Author(s):  
Wen Wang ◽  
You Zhou ◽  
Yangqian Cai ◽  
Sisi Wang ◽  
Fangbing Shao ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Dorsal Root ◽  
Protein Microarray ◽  
Mammalian Target Of Rapamycin ◽  
Bone Destruction ◽  
Bone Cancer ◽  
Mtor Signaling ◽  
Bone Cancer Pain ◽  
Underlying Mechanisms ◽  
Mixed Pain

Bone cancer pain (BCP) is a clinical refractory mixed pain involving neuropathic and inflammatory pain, with the underlying mechanisms remaining largely unknown. Electro-acupuncture (EA) can partly alleviate BCP according to previous research. We aim to explore the proteins and major pathways involved in BCP and EA treatment through phosphoproteomic profiling. BCP rat model was built by tibial inoculation of MRMT-1 mammary gland carcinoma cells. Mechanical hyperalgesia determined by paw withdrawal thresholds (PWTs) and bone destruction manifested on the radiographs confirmed the success of modeling, which were attenuated by EA treatment. The differentially expressed phosphorylated proteins (DEPs) co-regulated by BCP modeling and EA treatment in rat dorsal root ganglions (DRGs) were analyzed through PEX100 Protein microarray. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that DEPs were significantly enriched in mammalian target of rapamycin (mTOR) signaling pathway. The phosphorylations of mTOR at Ser2448 and Thr2446 were increased in BCP and downregulated by EA. In addition, the phosphorylation of S6K and Akt, markers of the mTOR complex, were also increased in BCP and downregulated by EA. Inhibition of mTOR signaling alleviated the PWTs of BCP rats, while the mTOR agonist impaired the analgesic effect of EA. Thus, our study provided a landscape of protein phosphorylation changes in DRGs of EA-treated BCP rats and revealed that mTOR signaling can be potentially targeted to alleviate BCP by EA treatment.

scholarly journals Curcumin Exerts Antinociceptive Effects in Cancer-Induced Bone Pain via an Endogenous Opioid Mechanism

2021 ◽  
Vol 15 ◽  
Author(s):  
Guanghai Zhao ◽  
Yongqiang Shi ◽  
Chaoyang Gong ◽  
Taicong Liu ◽  
Wei Nan ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Bone Pain ◽  
Antinociceptive Effect ◽  
Bone Cancer ◽  
Bone Cancer Pain ◽  
Drg Neurons ◽  
Advanced Cancer Patients ◽  
Endogenous Opioid ◽  
Analgesic Effects ◽  
Antinociceptive Effects

Cancer pain is one of the main complications in advanced cancer patients, and its management is still challenging. Therefore, there is an urgent need to develop novel pharmacotherapy for cancer pain. Several natural products have attracted the interest of researchers. In previous studies, curcumin has proved to exhibit antitumor, antiviral, antioxidant, anti-inflammatory, and analgesic effects. However, the analgesic mechanism of curcumin has not been elucidated. Thus, in this study, we aimed to elucidate the antinociceptive potency and analgesic mechanism of curcumin in cancer-induced bone pain. Our results showed that consecutive curcumin treatment (30, 60, 120 mg/kg, i.p., twice daily for 11 days) produced significant analgesic activity, but had no effect on the progress of the bone cancer pain. Notably, pretreatment with naloxone, a non-selective opioid receptor antagonist, markedly reversed the antinociceptive effect induced by curcumin. Moreover, in primary cultured rat dorsal root ganglion (DRG) neurons, curcumin significantly up-regulated the expression of proopiomelanocortin (Pomc) and promoted the release of β-endorphin and enkephalin. Furthermore, pretreatment with the antiserum of β-endorphin or enkephalin markedly attenuated curcumin-induced analgesia in cancer-induced bone pain. Our present study, for the first time, showed that curcumin attenuates cancer-induced bone pain. The results also suggested that stimulation of expression of DRG neurons β-endorphin and enkephalin mediates the antinociceptive effect of curcumin in pain hypersensitivity conditions.

scholarly journals STING suppresses cancer pain via immune and neuronal modulation

2021 ◽  
Author(s):  
Kaiyuan Wang ◽  
Christopher R. Donnelly ◽  
Changyu Jiang ◽  
Yihan Liao ◽  
Xueshu Tao ◽  
...  
Keyword(s):  
Pain Relief ◽  
Cancer Pain ◽  
Immune Cell ◽  
Bone Destruction ◽  
Bone Cancer ◽  
Tumor Burden ◽  
Bone Cancer Pain ◽  
Local Tumor ◽  
Nociceptive Neurons ◽  
Local Bone

AbstractAgonists of the innate immune regulator stimulator of interferon genes (STING) have shown great efficacy in promoting antitumor immunity in preclinical models, leading to their exploration in cancer immunotherapy trials. Patients with advanced stage cancers frequently suffer from severe pain as a result of bone metastasis and bone destruction, for which there is no efficacious treatment. Here, using multiple mouse models of metastatic bone cancer, we report that STING agonists confer remarkable protection against cancer pain, bone destruction, and local tumor burden. Repeated systemic administration of STING agonists robustly attenuated bone cancer-induced pain symptoms and improved locomotor function. Interestingly, STING agonists provided acute pain relief through direct neuronal modulation, as ex vivo incubation of STING agonists reduced excitability of pain-sensing nociceptive neurons from tumor-bearing mice. In addition, STING agonists protected local bone destruction and reduced local tumor burden through modulation of osteoclast and immune cell function in the tumor microenvironment, providing long-term cancer pain relief. Finally, these in vivo effects were dependent on host-intrinsic STING and Ifnar1. Overall, STING activation provides unique advantages in controlling metastatic bone cancer pain through distinct and synergistic actions on nociceptors, immune cells, and osteoclasts.

Mechanisms of bone cancer pain

2018 ◽  
Author(s):  
Louis Doré-Savard ◽  
Nicolas Beaudet ◽  
Philippe Sarret
Keyword(s):  
Nerve Growth Factor ◽  
Cancer Pain ◽  
Bone Pain ◽  
Bone Cancer ◽  
Bone Cancer Pain ◽  
Bone Microenvironment ◽  
Pain Syndromes ◽  
Peripheral Innervation ◽  
Promising Treatment ◽  
Skeletal Pain

The landmark paper discussed in this chapter focuses on pain arising from malignancy of the bone, which, whether primary or originating from a distant site, is the cause for a majority of cancer pain syndromes. Bone is an innervated organ that can relay nociceptive signals triggered by nerve damage, acidosis, inflammation, and hypoxia. The understanding of the physiopathology of skeletal pain has leaped significantly forwards over the last 15 years. The development of animal models that allowed for the visualization of bone microenvironment modifications by the tumour played an important role in recent advances. One of the most significant discoveries was the contribution of local nerve growth factor (NGF) to nerve remodelling in the bone periosteum presented by Mantyh and colleagues in 2010. NGF remains one the most promising treatment avenues for malignant bone pain, and peripheral innervation has become a therapeutic target in several skeletal pathologies.

scholarly journals STING suppresses bone cancer pain via immune and neuronal modulation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kaiyuan Wang ◽  
Christopher R. Donnelly ◽  
Changyu Jiang ◽  
Yihan Liao ◽  
Xin Luo ◽  
...  
Keyword(s):  
Pain Relief ◽  
Cancer Pain ◽  
Cell Function ◽  
Immune Cell ◽  
Bone Destruction ◽  
Bone Cancer ◽  
Tumor Burden ◽  
Bone Cancer Pain ◽  
Local Tumor ◽  
Local Bone

AbstractPatients with advanced stage cancers frequently suffer from severe pain as a result of bone metastasis and bone destruction, for which there is no efficacious treatment. Here, using multiple mouse models of bone cancer, we report that agonists of the immune regulator STING (stimulator of interferon genes) confer remarkable protection against cancer pain, bone destruction, and local tumor burden. Repeated systemic administration of STING agonists robustly attenuates bone cancer-induced pain and improves locomotor function. Interestingly, STING agonists produce acute pain relief through direct neuronal modulation. Additionally, STING agonists protect against local bone destruction and reduce local tumor burden through modulation of osteoclast and immune cell function in the tumor microenvironment, providing long-term cancer pain relief. Finally, these in vivo effects are dependent on host-intrinsic STING and IFN-I signaling. Overall, STING activation provides unique advantages in controlling bone cancer pain through distinct and synergistic actions on nociceptors, immune cells, and osteoclasts.

Sign in / Sign up

Export Citation Format

Share Document