Alleviation of neuropathic pain by over‐expressing a soluble colony‐stimulating factor 1 receptor to suppress microgliosis and macrophage accumulation

Glia ◽  
2021 ◽  
Author(s):  
Svetlana Gushchina ◽  
Ping K. Yip ◽  
Glesni A. Parry ◽  
Haripriya Sivakumar ◽  
Jie Li ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Colony Stimulating Factor ◽  
Stimulating Factor ◽  
Macrophage Accumulation

scholarly journals Alleviation of neuropathic pain by over-expressing a soluble colony-stimulating factor 1 receptor

2020 ◽  
Author(s):  
Svetlana Gushchina ◽  
Ping K. Yip ◽  
Glesni A. Parry ◽  
Haripriya Sivakumar ◽  
Jie Li ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Viral Vector ◽  
Colony Stimulating Factor ◽  
Withdrawal Threshold ◽  
Sciatic Nerves ◽  
Novel Strategy ◽  
Behavioural Tests ◽  
Lumbar Spinal ◽  
Stimulating Factor ◽  
Macrophage Accumulation

AbstractIn this study, we aim to alleviate neuropathic pain by suppressing microgliosis and macrophage accumulation, which is achieved by over-expressing a non-functional soluble colony-stimulating factor 1 receptor using adeno-associated virus 9 vectors (AAV9/sCSF1R). AAV9/sCSF1R and AAV9/GFP were intrathecally administered into mouse lumbar spine. Two weeks later, these mice underwent partial sciatic nerve ligation to induce neuropathic pain. GFP and sCSF1R were highly expressed in dorsal root ganglia (DRG) and spinal cords in AAV9-injected mice. Nerve ligation alone or pre-treated with AAV9/GFP led to significant microgliosis in the lumbar spinal cords and macrophage accumulation in DRG and sciatic nerves. In nerve-ligated mice pre- treated with AAV9/sCSF1R the microglia densities in the dorsal and ventral horns and macrophage densities in DRG and sciatic nerves were significantly lower compared to nerve-ligated mice pre-treated with AAV9/GFP. Behavioural tests showed that nerve-ligated mice pre- treated with AAV9/sCSF1R had a significantly higher paw withdrawal threshold, indicating the alleviation of neuropathic pain. The results implicate that viral vector-mediated expression of sCSF1R may represent a novel strategy in long-term alleviation of neuropathic pain.

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.

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 Interactions between Autophagy, Proinflammatory Cytokines and Apoptosis in Neuropathic Pain: Granulocyte Colony Stimulating Factor as a Multipotent Therapy in Rats with Chronic Constriction Injury

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 542
Author(s):  
Ming-Feng Liao ◽  
Shin-Rung Yeh ◽  
Kwok-Tung Lu ◽  
Jung-Lung Hsu ◽  
Po-Kuan Chao ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Protein Expression ◽  
Proinflammatory Cytokines ◽  
Early Phase ◽  
Chronic Constriction Injury ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Drg Neurons ◽  
Stimulating Factor

Our previous studies have shown that early systemic granulocyte colony-stimulating factor (G-CSF) treatment can attenuate neuropathic pain in rats with chronic constriction injury (CCI) by modulating expression of different proinflammatory cytokines, microRNAs, and proteins. Besides the modulation of inflammatory mediators’ expression, previous studies have also reported that G-CSF can modulate autophagic and apoptotic activity. Furthermore, both autophagy and apoptosis play important roles in chronic pain modulation. In this study, we evaluated the temporal interactions of autophagy, and apoptosis in the dorsal root ganglion (DRG) and injured sciatic nerve after G-CSF treatment in CCI rats. We studied the behaviors of CCI rats with or without G-CSF treatment and the various levels of autophagic, proinflammatory, and apoptotic proteins in injured sciatic nerves and DRG neurons at different time points using Western blot analysis and immunohistochemical methods. The results showed that G-CSF treatment upregulated autophagic protein expression in the early phase and suppressed apoptotic protein expression in the late phase after nerve injury. Thus, medication such as G-CSF can modulate autophagy, apoptosis, and different proinflammatory proteins in the injured sciatic nerve and DRG neurons, which have the potential to treat neuropathic pain. However, autophagy-mediated regulation of neuropathic pain is a time-dependent process. An increase in autophagic activity in the early phase before proinflammatory cytokines reach the threshold level to induce neuropathic pain can effectively alleviate further neuropathic pain development.

scholarly journals Tubulointerstitial Macrophage Accumulation is Regulated by Sequentially Expressed Osteopontin and Macrophage Colony-Stimulating Factor: Implication for the Role of Atorvastatin

2006 ◽  
Vol 2006 ◽  
pp. 1-9 ◽  
Author(s):  
Shaojiang Tian ◽  
Guohua Ding ◽  
Ruhan Jia ◽  
Guili Chu
Keyword(s):  
Treatment Group ◽  
Time Course ◽  
Interstitial Fibrosis ◽  
Statin Treatment ◽  
Histological Evaluation ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Macrophage Accumulation

Infiltration and local proliferation are known factors that contribute to tubulointerstitial macrophage accumulation. This study explored the time course of these two contributors' roles as tubulointerstitial inflammation and fibrosis progressing, and evaluated the mechanisms of the protective effect of atorvastatin. Unilateral ureteral obstructive (UUO) rats were treated with atorvastatin (10 mg/Kg) or vehicle. Expression of osteopontin (OPN) and macrophage colony-stimulating factor (M-CSF) was evaluated by RT-PCR and immunohistochemistry. Immunohistochemistry staining of ED1 was used to assess macrophage accumulation in interstitium. Histological evaluation was performed to semiquantify tubulointerstitial fibrosis. The results showed that on day 3 after UUO operation, OPN expression significantly increased and positively correlated with the number of the interstitial ED1+cells, while on day 10, M-CSF expression upregulated and correlated with interstitial ED1+cells. In atorvastatin treatment group, the increments of these two factors were attenuated significantly at the two time points, respectively. ED1+cell accumulation and fibrosis also ameliorated in the treatment group. For all the samples of UUO and treatment group on day 10, ED1+cells also correlated with interstitial fibrosis scores. The results suggest that OPN may induce the early macrophage/monocyte infiltration and M-CSF may play an important role in regulating macrophage accumulation in later stage of UUO nephropathy. Statin treatment decreases interstitial inflammation and fibrosis, and this renoprotective effect may be mediated by downregulating the expression of OPN and M-CSF.

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