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

Sun, Yue; Tian, Yuan; Li, Haifeng; Zhang, Dengwen; Sun, Qiang

doi:10.1155/2017/7346103

Cited by 12 publications

(8 citation statements)

References 38 publications

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“…Several previous studies have established that pERK expression levels are elevated in the lumbar spinal cord of rats receiving a unilateral ITI of Walker 256 cells, in the pain state (Wang L.-n. et al, 2011 ; Chen et al, 2012 ; Hu et al, 2015 ; Zhu et al, 2015 ; Ding et al, 2017 ; Sun et al, 2017 ). In BCIBP-rats administered a bolus dose of J-2156 at 10 mg/kg i.p., pERK expression levels in the lumbar spinal dorsal horns at the time of peak effect of anti-hypersensitivity were significantly ( p ≤ 0.05) decreased c.f .…”

Section: Resultsmentioning

confidence: 99%

The Somatostatin Receptor-4 Agonist J-2156 Alleviates Mechanical Hypersensitivity in a Rat Model of Breast Cancer Induced Bone Pain

et al. 2018

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In the majority of patients with breast cancer in the advanced stages, skeletal metastases are common, which may cause excruciating pain. Currently available drug treatments for relief of breast cancer-induced bone pain (BCIBP) include non-steroidal anti-inflammatory drugs and strong opioid analgesics along with inhibitors of osteoclast activity such as bisphosphonates and monoclonal antibodies such as denosumab. However, these medications often lack efficacy and/or they may produce serious dose-limiting side effects. In the present study, we show that J-2156, a somatostatin receptor type 4 (SST4 receptor) selective agonist, reverses pain-like behaviors in a rat model of BCIBP induced by unilateral intra-tibial injection of Walker 256 breast cancer cells. Following intraperitoneal administration, the ED50 of J-2156 for the relief of mechanical allodynia and mechanical hyperalgesia in the ipsilateral hindpaws was 3.7 and 8.0 mg/kg, respectively. Importantly, the vast majority of somatosensory neurons in the dorsal root ganglia including small diameter C-fibers and medium-large diameter fibers, that play a crucial role in cancer pain hypersensitivities, expressed the SST4 receptor. J-2156 mediated pain relief in BCIBP-rats was confirmed by observations of a reduction in the levels of phosphorylated extracellular signal-regulated kinase (pERK), a protein essential for central sensitization and persistent pain, in the spinal dorsal horn. Our results demonstrate the potential of the SST4 receptor as a pharmacological target for relief of BCIBP and we anticipate the present work to be a starting point for further mechanism-based studies.

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Section: Resultsmentioning

confidence: 99%

The Somatostatin Receptor-4 Agonist J-2156 Alleviates Mechanical Hypersensitivity in a Rat Model of Breast Cancer Induced Bone Pain

et al. 2018

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“…Moreover, several studies have shown attenuation of BCP in rats. These studies included overexpression of suppressor of cytokine signaling 3 in DRG, 15 suppression of asparaginyl endopeptidase in cancer cells, intrathecal injection of genetically engineered human bone marrow stem cells expressing the proenkephalin gene, 20 and intraperitoneal administration of a somatostatin receptor type 4 selective agonist, J-2156. However, comprehensive gene expression profiling of DRGs in a BCP model has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of bone morphogenetic protein 2 (Bmp2) in dorsal root ganglion in a rat model of bone cancer pain

Wang

Jiang

et al. 2019

Mol Pain

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Bone cancer pain is one of the most severe and intractable complications in patients suffering from primary or metastatic bone cancer and profoundly compromises the quality of life. Emerging evidence indicates that the dorsal root ganglion play an integral role in the modulation of pain hypersensitivity. However, the underlying molecular mechanisms during dorsal root ganglion-mediated bone cancer pain remain elusive. In this study, RNA-sequencing was used to detect the differentially expressed genes in dorsal root ganglion neurons of a rat bone cancer pain model established by intratibial inoculation of Walker 256 breast cancer cells. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that the differentially expressed genes (fold change > 1.5; false discovery rate < 0.05) were enriched in the bone morphogenetic protein (BMP) signaling pathway, transforming growth factor-β signaling pathway, and positive regulation of cartilage development. Importantly, serum deprivation-response protein (Sdpr), hephaestin (Heph), transthyretin (Ttr), insulin receptor substrate 1 (Irs1), connective tissue growth factor (Ctgf ), and Bmp2 genes were associated with bone pain and degeneration. Of note, Bmp2, a pleiotropic and secreted molecule mediating pain and inflammation, was one of the most significantly upregulated genes in dorsal root ganglion neurons in this bone cancer pain model. Consistent with these data, upregulation of Bmp2 in the bone cancer pain model was validated by immunohistochemistry, real-time quantitative polymerase chain reaction, and western blotting. Importantly, intrathecal administration of siRNA significantly reduced Bmp2 transcription and ameliorated bone cancer pain in rat as shown by paw withdrawal mechanical threshold and spontaneous and movement-evoked pain-like behaviors. In conclusion, we have characterized the comprehensive gene expression profile of dorsal root ganglion from a bone cancer pain rat model by RNA-sequencing and identified Bmp2 as a potential therapeutic target for bone cancer pain treatment.

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“…Injection of autologous MSCs into the joint alleviated pain in patients with osteoarthritis (20). Intrathecal injection of bioengineered MSCs has been shown to exert antinociceptive effects in animal models of bone cancer pain (21). Cell-based pain therapy might represent a promising option to treat chronic pain.…”

mentioning

confidence: 99%

Immunotherapy for the management of cancer pain

Amaya

2020

Ann Palliat Med

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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

Cited by 12 publications

References 38 publications

The Somatostatin Receptor-4 Agonist J-2156 Alleviates Mechanical Hypersensitivity in a Rat Model of Breast Cancer Induced Bone Pain

The Somatostatin Receptor-4 Agonist J-2156 Alleviates Mechanical Hypersensitivity in a Rat Model of Breast Cancer Induced Bone Pain

Upregulation of bone morphogenetic protein 2 (Bmp2) in dorsal root ganglion in a rat model of bone cancer pain

Immunotherapy for the management of cancer pain

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