Interactions between autophagy, proinflammatory cytokines, and apoptosis in neuropathic pain: Granulocyte colony stimulating factor as a multipotent therapy in rats with chronic constriction injury

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number542
JournalBiomedicines
Volume9
Issue number5
DOIs
Publication statusPublished - 2021 May

Keywords

  • Apoptosis
  • Autophagy
  • Chronic constriction injury
  • Granulocyte colony stimulating factor
  • Neuropathic pain
  • Proinflammatory cytokine

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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