Epigenetic reduction of miR-214-3p upregulates astrocytic colony-stimulating factor-1 and contributes to neuropathic pain induced by nerve injury

Pain ◽  
2020 ◽  
Vol 161 (1) ◽  
pp. 96-108 ◽  
Author(s):  
Lian Liu ◽  
Dan Xu ◽  
Tao Wang ◽  
Yi Zhang ◽  
Xijing Yang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Colony Stimulating Factor ◽  
Stimulating Factor

scholarly journals Receptor dependence of BDNF actions in superficial dorsal horn: relation to central sensitization and actions of macrophage colony stimulating factor 1

2019 ◽  
Vol 121 (6) ◽  
pp. 2308-2322 ◽  
Author(s):  
Paul A. Boakye ◽  
Vladimir Rancic ◽  
Kerri H. Whitlock ◽  
Danielle Simmons ◽  
Frank M. Longo ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Central Sensitization ◽  
Inhibitory Neurons ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Excitatory Drive

Peripheral nerve injury elicits an enduring increase in the excitability of the spinal dorsal horn. This change, which contributes to the development of neuropathic pain, is a consequence of release and prolonged exposure of dorsal horn neurons to various neurotrophins and cytokines. We have shown in rats that nerve injury increases excitatory synaptic drive to excitatory neurons but decreases drive to inhibitory neurons. Both effects, which contribute to an increase in dorsal horn excitability, appear to be mediated by microglia-derived BDNF. We have used multiphoton Ca2+ imaging and whole cell recording of spontaneous excitatory postsynaptic currents in defined-medium organotypic cultures of GAD67-GFP+ mice spinal cord to determine the receptor dependence of these opposing actions of BDNF. In mice, as in rats, BDNF enhances excitatory transmission onto excitatory neurons. This is mediated via presynaptic TrkB and p75 neurotrophin receptors and exclusively by postsynaptic TrkB. By contrast with findings from rats, in mice BDNF does not decrease excitation of inhibitory neurons. The cytokine macrophage colony-stimulating factor 1 (CSF-1) has also been implicated in the onset of neuropathic pain. Nerve injury provokes its de novo synthesis in primary afferents, its release in spinal cord, and activation of microglia. We now show that CSF-1 increases excitatory drive to excitatory neurons via a BDNF-dependent mechanism and decreases excitatory drive to inhibitory neurons via BDNF-independent processes. Our findings complete missing steps in the cascade of events whereby peripheral nerve injury instigates increased dorsal horn excitability in the context of central sensitization and the onset of neuropathic pain. NEW & NOTEWORTHY Nerve injury provokes synthesis of macrophage colony-stimulating factor 1 (CSF-1) in primary afferents and its release in the dorsal horn. We show that CSF-1 increases excitatory drive to excitatory dorsal horn neurons via BDNF activation of postsynaptic TrkB and presynaptic TrkB and p75 neurotrophin receptors. CSF-1 decreases excitatory drive to inhibitory neurons via a BDNF-independent processes. This completes missing steps in understanding how peripheral injury instigates central sensitization and the onset of neuropathic pain.

scholarly journals Granulocyte Colony Stimulating Factor (GCSF) Can Attenuate Neuropathic Pain by Suppressing Monocyte Chemoattractant Protein-1 (MCP-1) Expression, through Upregulating the Early MicroRNA-122 Expression in the Dorsal Root Ganglia

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1669 ◽  
Author(s):  
Ming-Feng Liao ◽  
Jung-Lung Hsu ◽  
Kwok-Tung Lu ◽  
Po-Kuan Chao ◽  
Mei-Yun Cheng ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Stimulating Factor

Our previous animal studies and several human clinical trials have shown that granulocyte-colony stimulating factor (GCSF) can attenuate neuropathic pain through various mechanisms. GCSF itself is also a multipotent cytokine that can modulate microribonucleic acid (microRNA) expression profiles in vitro. In this study, we used the NanoString nCounter analysis system to screen the expression of different rodent microRNAs at early stage after nerve injury and studied the expression of related cytokines/chemokines in the dorsal root ganglia (DRGs) of rats that underwent chronic constriction injury (CCI) to explore the underlying mechanisms of the analgesic effects of GCSF. We found that microRNA-122 expression was downregulated by CCI; in contrast, GCSF treatment significantly upregulated microRNA-122 expression in the DRGs of CCI rats on the 1st day after nerve injury. We further studied the expression of different cytokines/chemokines (IL-1β, IL-6, and monocyte chemoattractant protein-1 (MCP-1)) that were modulated by microRNA-122. MCP-1 has been reported to participate in neuropathic pain development, and its expression on the DRGs of vehicle-treated CCI rats was significantly higher than that on the DRGs of sham-operated rats; in contrast, GCSF-treated rats exhibited significantly lower MCP-1 expression in the DRG than vehicle-treated rats on the 7th day after nerve injury. An early GCSF treatment can suppress MCP-1 expressions, through upregulating microRNA-122 expressions in the DRGs of CCI rats at an earlier stage, thus indirectly attenuating neuropathic pain development.

scholarly journals Central inhibition of granulocyte-macrophage colony-stimulating factor is analgesic in experimental neuropathic pain

Pain ◽  
2018 ◽  
Vol 159 (3) ◽  
pp. 550-559 ◽  
Author(s):  
Louise S.C. Nicol ◽  
Peter Thornton ◽  
Jon P. Hatcher ◽  
Colin P. Glover ◽  
Carl I. Webster ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Colony Stimulating Factor ◽  
Central Inhibition ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Phase I Study of Chimeric Human/Murine Anti–Ganglioside GD2Monoclonal Antibody (ch14.18) With Granulocyte-Macrophage Colony-Stimulating Factor in Children With Neuroblastoma Immediately After Hematopoietic Stem-Cell Transplantation: A Children’s Cancer Group Study

2000 ◽  
Vol 18 (24) ◽  
pp. 4077-4085 ◽  
Author(s):  
M. Fevzi Ozkaynak ◽  
Paul M. Sondel ◽  
Mark D. Krailo ◽  
Jacek Gan ◽  
Brad Javorsky ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Neuroblastoma Cells ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

PURPOSE: Ganglioside GD2is strongly expressed on the surface of human neuroblastoma cells. It has been shown that the chimeric human/murine anti-GD2monoclonal antibody (ch14.18) can induce lysis of neuroblastoma cells by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. The purposes of the study were (1) to determine the maximum-tolerated dose (MTD) of ch14.18 in combination with standard dose granulocyte-macrophage colony-stimulating factor (GM-CSF) for patients with neuroblastoma who recently completed hematopoietic stem-cell transplantation (HSCT), and (2) to determine the toxicities of ch14.18 with GM-CSF in this setting.PATIENTS AND METHODS: Patients became eligible when the total absolute phagocyte count (APC) was greater than 1,000/μL after HSCT. ch14.18 was infused intravenously over 5 hours daily for 4 consecutive days. Patients received GM-CSF 250 μg/m2/d starting at least 3 days before ch14.18 and continued for 3 days after the completion of ch14.18. The ch14.18 dose levels were 20, 30, 40, and 50 mg/m2/d. In the absence of progressive disease, patients were allowed to receive up to six 4-day courses of ch14.18 therapy with GM-CSF. Nineteen patients with neuroblastoma were treated.RESULTS: A total of 79 courses were administered. No toxic deaths occurred. The main toxicities were severe neuropathic pain, fever, nausea/vomiting, urticaria, hypotension, mild to moderate capillary leak syndrome, and neurotoxicity. Three dose-limiting toxicities were observed among six patients at 50 mg/m2/d: intractable neuropathic pain, grade 3 recurrent urticaria, and grade 4 vomiting. Human antichimeric antibody developed in 28% of patients.CONCLUSION: ch14.18 can be administered with GM-CSF after HSCT in patients with neuroblastoma with manageable toxicities. The MTD is 40 mg/m2/d for 4 days when given in this schedule with GM-CSF.

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