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

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 o...

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Main Authors: Ming-Feng Liao, Shin-Rung Yeh, Kwok-Tung Lu, Jung-Lung Hsu, Po-Kuan Chao, Hui-Ching Hsu, Chi-Hao Peng, Yun-Lin Lee, Yu-Hui Hung, Long-Sun Ro
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/9/5/542
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author Ming-Feng Liao
Shin-Rung Yeh
Kwok-Tung Lu
Jung-Lung Hsu
Po-Kuan Chao
Hui-Ching Hsu
Chi-Hao Peng
Yun-Lin Lee
Yu-Hui Hung
Long-Sun Ro
author_facet Ming-Feng Liao
Shin-Rung Yeh
Kwok-Tung Lu
Jung-Lung Hsu
Po-Kuan Chao
Hui-Ching Hsu
Chi-Hao Peng
Yun-Lin Lee
Yu-Hui Hung
Long-Sun Ro
author_sort Ming-Feng Liao
collection DOAJ
description 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.
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spelling doaj.art-8fde1ec2b67d46478e9f654ed845d8b52023-11-21T19:25:44ZengMDPI AGBiomedicines2227-90592021-05-019554210.3390/biomedicines9050542Interactions between Autophagy, Proinflammatory Cytokines, and Apoptosis in Neuropathic Pain: Granulocyte Colony Stimulating Factor as a Multipotent Therapy in Rats with Chronic Constriction InjuryMing-Feng Liao0Shin-Rung Yeh1Kwok-Tung Lu2Jung-Lung Hsu3Po-Kuan Chao4Hui-Ching Hsu5Chi-Hao Peng6Yun-Lin Lee7Yu-Hui Hung8Long-Sun Ro9Department of Neurology, Chang Gung Memorial Hospital, College of Medicine, Linkou Medical Center and Chang Gung University, Taipei 33305, TaiwanCollege of Life Science, National Tsing Hua University, Hsinchu 30013, TaiwanDepartment of Life Science, National Taiwan Normal University, Taipei 11677, TaiwanDepartment of Neurology, Chang Gung Memorial Hospital, College of Medicine, Linkou Medical Center and Chang Gung University, Taipei 33305, TaiwanInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 35053, TaiwanDivision of Chinese Acupuncture and Traumatology, Chang Department of Traditional Chinese Medicine, Gung Memorial Hospital, College of Medicine, Linkou Medical Center and Chang Gung University, Taipei 33305, TaiwanDivision of Chinese Acupuncture and Traumatology, Chang Department of Traditional Chinese Medicine, Gung Memorial Hospital, College of Medicine, Linkou Medical Center and Chang Gung University, Taipei 33305, TaiwanDepartment of Neurology, Chang Gung Memorial Hospital, College of Medicine, Linkou Medical Center and Chang Gung University, Taipei 33305, TaiwanDepartment of Neurology, Chang Gung Memorial Hospital, College of Medicine, Linkou Medical Center and Chang Gung University, Taipei 33305, TaiwanDepartment of Neurology, Chang Gung Memorial Hospital, College of Medicine, Linkou Medical Center and Chang Gung University, Taipei 33305, TaiwanOur 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.https://www.mdpi.com/2227-9059/9/5/542neuropathic paingranulocyte colony stimulating factorchronic constriction injuryautophagyapoptosisproinflammatory cytokine
spellingShingle Ming-Feng Liao
Shin-Rung Yeh
Kwok-Tung Lu
Jung-Lung Hsu
Po-Kuan Chao
Hui-Ching Hsu
Chi-Hao Peng
Yun-Lin Lee
Yu-Hui Hung
Long-Sun Ro
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
neuropathic pain
granulocyte colony stimulating factor
chronic constriction injury
autophagy
apoptosis
proinflammatory cytokine
title Interactions between Autophagy, Proinflammatory Cytokines, and Apoptosis in Neuropathic Pain: Granulocyte Colony Stimulating Factor as a Multipotent Therapy in Rats with Chronic Constriction Injury
title_full Interactions between Autophagy, Proinflammatory Cytokines, and Apoptosis in Neuropathic Pain: Granulocyte Colony Stimulating Factor as a Multipotent Therapy in Rats with Chronic Constriction Injury
title_fullStr Interactions between Autophagy, Proinflammatory Cytokines, and Apoptosis in Neuropathic Pain: Granulocyte Colony Stimulating Factor as a Multipotent Therapy in Rats with Chronic Constriction Injury
title_full_unstemmed Interactions between Autophagy, Proinflammatory Cytokines, and Apoptosis in Neuropathic Pain: Granulocyte Colony Stimulating Factor as a Multipotent Therapy in Rats with Chronic Constriction Injury
title_short Interactions between Autophagy, Proinflammatory Cytokines, and Apoptosis in Neuropathic Pain: Granulocyte Colony Stimulating Factor as a Multipotent Therapy in Rats with Chronic Constriction Injury
title_sort interactions between autophagy proinflammatory cytokines and apoptosis in neuropathic pain granulocyte colony stimulating factor as a multipotent therapy in rats with chronic constriction injury
topic neuropathic pain
granulocyte colony stimulating factor
chronic constriction injury
autophagy
apoptosis
proinflammatory cytokine
url https://www.mdpi.com/2227-9059/9/5/542
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