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

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2021 Jun 2

PMID 34066206

Citations 6

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

Affiliations

Soon will be listed here.

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.

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References

Berliocchi L, Russo R, Maiaru M, Levato A, Bagetta G, Corasaniti M . Autophagy impairment in a mouse model of neuropathic pain. Mol Pain. 2011; 7:83. PMC: 3234188. DOI: 10.1186/1744-8069-7-83. View

Anderlini P, Przepiorka D, Champlin R, Korbling M . Biologic and clinical effects of granulocyte colony-stimulating factor in normal individuals. Blood. 1996; 88(8):2819-25. View

Campana W, Myers R . Exogenous erythropoietin protects against dorsal root ganglion apoptosis and pain following peripheral nerve injury. Eur J Neurosci. 2003; 18(6):1497-506. DOI: 10.1046/j.1460-9568.2003.02875.x. View

Wan J, Ma J, Anand V, Ramakrishnan S, Roy S . Morphine potentiates LPS-induced autophagy initiation but inhibits autophagosomal maturation through distinct TLR4-dependent and independent pathways. Acta Physiol (Oxf). 2015; 214(2):189-199. PMC: 4430349. DOI: 10.1111/apha.12506. View

Kato K, Koda M, Takahashi H, Sakuma T, Inada T, Kamiya K . Granulocyte colony-stimulating factor attenuates spinal cord injury-induced mechanical allodynia in adult rats. J Neurol Sci. 2015; 355(1-2):79-83. DOI: 10.1016/j.jns.2015.05.024. View

Ma Z, Han Q, Wang X, Ai Z, Zheng Y . Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury. PLoS One. 2016; 11(2):e0148792. PMC: 4752273. DOI: 10.1371/journal.pone.0148792. View

Wiberg R, Novikova L, Kingham P . Evaluation of apoptotic pathways in dorsal root ganglion neurons following peripheral nerve injury. Neuroreport. 2018; 29(9):779-785. DOI: 10.1097/WNR.0000000000001031. View

Bennett G, Xie Y . A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 1988; 33(1):87-107. DOI: 10.1016/0304-3959(88)90209-6. View

Menzie-Suderam J, Modi J, Xu H, Bent A, Trujillo P, Medley K . Granulocyte-colony stimulating factor gene therapy as a novel therapeutics for stroke in a mouse model. J Biomed Sci. 2020; 27(1):99. PMC: 7596942. DOI: 10.1186/s12929-020-00692-5. View

10.

Schaeffer V, Meyer L, Patte-Mensah C, Eckert A, Mensah-Nyagan A . Sciatic nerve injury induces apoptosis of dorsal root ganglion satellite glial cells and selectively modifies neurosteroidogenesis in sensory neurons. Glia. 2009; 58(2):169-80. DOI: 10.1002/glia.20910. View

11.

Solaroglu I, Cahill J, Jadhav V, Zhang J . A novel neuroprotectant granulocyte-colony stimulating factor. Stroke. 2006; 37(4):1123-8. DOI: 10.1161/01.STR.0000208205.26253.96. View

12.

Khandia R, Dadar M, Munjal A, Dhama K, Karthik K, Tiwari R . A Comprehensive Review of Autophagy and Its Various Roles in Infectious, Non-Infectious, and Lifestyle Diseases: Current Knowledge and Prospects for Disease Prevention, Novel Drug Design, and Therapy. Cells. 2019; 8(7). PMC: 6678135. DOI: 10.3390/cells8070674. View

13.

White K, Dempsie Y, Caruso P, Wallace E, McDonald R, Stevens H . Endothelial apoptosis in pulmonary hypertension is controlled by a microRNA/programmed cell death 4/caspase-3 axis. Hypertension. 2014; 64(1):185-94. DOI: 10.1161/HYPERTENSIONAHA.113.03037. View

14.

Scheubel R, Bartling B, Simm A, Silber R, Drogaris K, Darmer D . Apoptotic pathway activation from mitochondria and death receptors without caspase-3 cleavage in failing human myocardium: fragile balance of myocyte survival?. J Am Coll Cardiol. 2002; 39(3):481-8. DOI: 10.1016/s0735-1097(01)01769-7. View

15.

Marinelli S, Nazio F, Tinari A, Ciarlo L, DAmelio M, Pieroni L . Schwann cell autophagy counteracts the onset and chronification of neuropathic pain. Pain. 2013; 155(1):93-107. DOI: 10.1016/j.pain.2013.09.013. View

16.

Zhao L, Zhu Y, Wang D, Chen M, Gao P, Xiao W . Morphine induces Beclin 1- and ATG5-dependent autophagy in human neuroblastoma SH-SY5Y cells and in the rat hippocampus. Autophagy. 2010; 6(3):386-94. DOI: 10.4161/auto.6.3.11289. View

17.

Li Y, Jiang J, Liu W, Wang H, Zhao L, Liu S . microRNA-378 promotes autophagy and inhibits apoptosis in skeletal muscle. Proc Natl Acad Sci U S A. 2018; 115(46):E10849-E10858. PMC: 6243236. DOI: 10.1073/pnas.1803377115. View

18.

Wang Y, Zhao H, Guo M, Fei D, Zhang L, Xing M . Targeting the miR-122/PKM2 autophagy axis relieves arsenic stress. J Hazard Mater. 2019; 383:121217. DOI: 10.1016/j.jhazmat.2019.121217. View

19.

Liu X, Zhu M, Ju Y, Li A, Sun X . Autophagy dysfunction in neuropathic pain. Neuropeptides. 2019; 75:41-48. DOI: 10.1016/j.npep.2019.03.005. View

20.

Modi J, Menzie-Suderam J, Xu H, Trujillo P, Medley K, Marshall M . Mode of action of granulocyte-colony stimulating factor (G-CSF) as a novel therapy for stroke in a mouse model. J Biomed Sci. 2020; 27(1):19. PMC: 6943893. DOI: 10.1186/s12929-019-0597-7. View