Intrathecal administration of SRT1720 relieves bone cancer pain by inhibiting the CREB/CRTC1 signalling pathway

In this study, we measured the analgesic effects of different intrathecal doses of SRT1720 on BCP in a murine model and further examined whether SRT1720 attenuated BCP by suppressing CREB/CREB-regulated transcription coactivator 1 (CRTC1) signalling pathway. Our results demonstrated that the BCP mice developed significant mechanical allodynia and spontaneous flinching, which were accompanied by the upregulation of phospho-Ser133 CREB (p-CREB) and CRTC1 expression in the spinal cord. SRT1720 treatment produced a dose-dependent analgesic effect on the BCP mice and downregulated the expression of p-CREB and CRTC1. These results suggest that intrathecal administration of SRT1720 reverses BCP likely by inhibiting the CREB/CRTC1 signalling pathway.
Source: Neuroscience Letters - Category: Neuroscience Source Type: research

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By SAURABH JHA, MD Slumdog TB No one knows who gave Rahul Roy tuberculosis. Roy’s charmed life as a successful trader involved traveling in his Mercedes C class between his apartment on the plush Nepean Sea Road in South Mumbai and offices in Bombay Stock Exchange. He cared little for Mumbai’s weather. He seldom rolled down his car windows – his ambient atmosphere, optimized for his comfort, rarely changed. Historically TB, or “consumption” as it was known, was a Bohemian malady; the chronic suffering produced a rhapsody which produced fine art. TB was fashionable in Victorian Britain...
Source: The Health Care Blog - Category: Consumer Health News Authors: Tags: Artificial Intelligence Health Tech Saurabh Jha TB tuberculosis Source Type: blogs
The original version of this article unfortunately contained a mistake in Fig. 2.
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research
This study investigated the role of SAP102 in the formation of hyperalgesia in rats with CIBP SAP102 is present in spinal dorsal horn neurons, but not in astrocytes or microglia. NMDAR-NR2B is localized with neurons. In addition, SAP102 and NMDAR-NR2B expression levels in spinal dorsal horn tissues were detected by Western blot and co-immunoprecipitation. Intrathecal injection of lentiviral vector of RNAi to knockdown SAP102 expression in the spinal dorsal horn significantly attenuated abnormal mechanic pain when compared to non-coding lentiviral vector. These findings indicate that SAP102 can anchor NMDA receptors to affe...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
Cannabinoid receptor 2‑selective agonist JWH015 attenuates bone cancer pain through the amelioration of impaired autophagy flux induced by inflammatory mediators in the spinal cord. Mol Med Rep. 2019 Oct 25;: Authors: Mao Y, Huang Y, Zhang Y, Wang C, Wu H, Tian X, Liu Y, Hou B, Liang Y, Rong H, Gu X, Ma Z Abstract Bone cancer pain (BCP) is a severe complication of advanced bone cancer. Although cannabinoid receptor 2 (CB2) agonists may have an analgesic effect, the underlying mechanism remains unclear. CB2 serves a protective role in various pathological states through the activation of autophagy. Th...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
This study tested the hypothesis that vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 contribute to bone cancer pain regulation associated with spinal central sensitization.Methods This study was performed on female rats using a metastatic breast cancer bone pain model. Nociceptive behaviors were evaluated by mechanical allodynia, thermal hyperalgesia, spontaneous pain, and CatWalk gait analysis. Expression levels were measured by real-time quantitative polymerase chain reaction, western blot, and immunofluorescence analysis. Excitatory synaptic transmission was detected by whole-cell...
Source: Anesthesiology - Category: Anesthesiology Source Type: research
Conclusion: Intrathecal group and intraperitoneal group showed significant difference in μ-opioid receptor expressions although with no difference in analgesia effects. Long-term intrathecal morphine administration provided similar analgesia compared to systemic morphine. PMID: 31662712 [PubMed]
Source: Dose Response - Category: Drugs & Pharmacology Authors: Tags: Dose Response Source Type: research
Abstract Mas-related G-protein-coupled receptor subtype C (MrgC) has been shown to play an important role in the development of bone cancer pain. Ubiquitination is reported to participate in pain. However, whether MrgC ubiquitination plays a role in bone cancer pain remains unclear. To answer this question, we designed and performed this study. Osteosarcoma cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce progressive bone cancer pain. MrgC agonist bovine adrenal medulla 8-22 (BAM 8-22) or MrgC antagonist anti-MrgC antibody were injected intrathecally on day 14 after ...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research
Blocks Bone Cancer PainAltered expression of circular RNA (circRNA) is recognized as a contributor to malignant pain where microRNA (miRNA) exerts an essential effect. Researchers used ouri-FectTMTransfection Kit to knock them down. Zhongqi Zhang, Xiaoxia Zhang, Yanjing Zhang, Jiyuan Li, Zumin Xing. Yiwen Zhang.Spinal circRNA-9119 Suppresses Nociception by Mediating the miR-26a-TLR3 Axis in a Bone Cancer Pain Mouse Model. Spinal circRNA-9119 Suppresses Nociception by Mediating the miR-26a-TLR3 Axis in a Bone Cancer Pain Mouse Model. Journal of Molecular Neuroscience. pp 1 –10Intrathecal Administration of miRNA and ci...
Source: Neuromics - Category: Neuroscience Tags: Bone Cancer Pain circRNA iFect miRNA Transfection Transfection Reagents Source Type: news
AbstractAltered expression of circular RNA (circRNA) is recognized as a contributor to malignant pain where microRNA (miRNA) exerts an essential effect. We generated a murine model for bone malignancy pain in which 2472 osteolytic sarcoma cells were injected into the femurs of mice. CircRNA microarray and quantitative PCR (qPCR) and revealed that circ9119 expression was repressed in the spinal cord of bone malignancy pain model mice, which is the first relay site involved in the transmission of nociceptive information to the cerebrum of mice that receive spinal analgesics for malignancy pain. Overexpression of circ9119 by ...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research
Conclusions: Knockdown of TRPV1 effectively ameliorated mechanical allodynia and thermal hyperalgesia induced by TCI. Our data demonstrated that modulate the expression of TRPV1 in the spinal cord could be a potential therapeutic approach for bone cancer pain. PMID: 31296147 [PubMed - as supplied by publisher]
Source: Neurological Research - Category: Neurology Tags: Neurol Res Source Type: research
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