PMID- 34572376
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211001
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 9
IP  - 9
DP  - 2021 Sep 10
TI  - Fumagillin Attenuates Spinal Angiogenesis, Neuroinflammation, and Pain in 
      Neuropathic Rats after Chronic Constriction Injury.
LID - 10.3390/biomedicines9091187 [doi]
LID - 1187
AB  - INTRODUCTION: Angiogenesis in the central nervous system is visible in animal 
      models of neuroinflammation and bone cancer pain. However, whether spinal 
      angiogenesis exists and contributes to central sensitization in neuropathic pain 
      remains unclear. This study analyzes the impact of angiogenesis on spinal 
      neuroinflammation in neuropathic pain. METHODS: Rats with chronic constriction 
      injury (CCI) to the sciatic nerve underwent the implantation of an intrathecal 
      catheter. Fumagillin or vascular endothelial growth factor-A antibody 
      (anti-VEGF-A) was administered intrathecally. Nociceptive behaviors, cytokine 
      immunoassay, Western blot, and immunohistochemical analysis assessed the effect 
      of angiogenesis inhibition on CCI-induced neuropathic pain. RESULTS: VEGF, 
      cluster of differentiation 31 (CD31), and von Willebrand factor (vWF) expressions 
      increased after CCI in the ipsilateral lumbar spinal cord compared to that in the 
      contralateral side of CCI and control rats from post-operative day (POD) 7 to 28, 
      with a peak at POD 14. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), 
      and IL-6 concentrations, but not IL-10 levels, also increased in the ipsilateral 
      spinal cord after CCI. Fumagillin and anti-VEGF-A reduced CCI-induced thermal 
      hyperalgesia from POD 5 to 14 and mechanical allodynia from POD 3 to 14. 
      Fumagillin reduced CCI-upregulated expressions of angiogenic factors and 
      astrocytes. Furthermore, fumagillin decreased TNF-alpha and IL-6 amounts and 
      increased IL-10 levels at POD 7 and 14, but not IL-1beta concentrations. 
      CONCLUSIONS: Fumagillin significantly ameliorates CCI-induced nociceptive 
      sensitization, spinal angiogenesis, and astrocyte activation. Our results suggest 
      that angiogenesis inhibitor treatment suppresses peripheral neuropathy-induced 
      central angiogenesis, neuroinflammation, astrocyte activation, and neuropathic 
      pain.
FAU - Wen, Zhi-Hong
AU  - Wen ZH
AUID- ORCID: 0000-0003-4411-044X
AD  - Department of Marine Biotechnology and Resources, National Sun Yat-sen 
      University, Kaohsiung 804201, Taiwan.
AD  - Institute of BioPharmaceutical Sciences, National Sun Yat-sen University, 
      Kaohsiung 804201, Taiwan.
FAU - Huang, Shi-Ying
AU  - Huang SY
AUID- ORCID: 0000-0002-0370-1553
AD  - College of Ocean Food and Biological Engineering, Jimei University, Xiamen 
      361021, China.
FAU - Kuo, Hsiao-Mei
AU  - Kuo HM
AUID- ORCID: 0000-0001-5749-7757
AD  - Department of Marine Biotechnology and Resources, National Sun Yat-sen 
      University, Kaohsiung 804201, Taiwan.
AD  - Center for Neuroscience, National Sun Yat-sen University, Kaohsiung 804201, 
      Taiwan.
FAU - Chen, Chao-Ting
AU  - Chen CT
AD  - Department of Marine Biotechnology and Resources, National Sun Yat-sen 
      University, Kaohsiung 804201, Taiwan.
FAU - Chen, Nan-Fu
AU  - Chen NF
AD  - Department of Surgery, Division of Neurosurgery, Kaohsiung Armed Forces General 
      Hospital, Kaohsiung 802301, Taiwan.
AD  - Institute of Medical Science and Technology, National Sun Yat-sen University, 
      Kaohsiung 804201, Taiwan.
FAU - Chen, Wu-Fu
AU  - Chen WF
AD  - Department of Marine Biotechnology and Resources, National Sun Yat-sen 
      University, Kaohsiung 804201, Taiwan.
AD  - Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung 
      University College of Medicine, Kaohsiung 833401, Taiwan.
FAU - Tsui, Kuan-Hao
AU  - Tsui KH
AD  - Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, 
      Kaohsiung 813414, Taiwan.
AD  - Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung 
      University, Taipei 112304, Taiwan.
FAU - Liu, Hsin-Tzu
AU  - Liu HT
AD  - Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi 
      Medical Foundation, Hualien 970473, Taiwan.
FAU - Sung, Chun-Sung
AU  - Sung CS
AD  - Department of Anesthesiology, Division of Pain Management, Taipei Veterans 
      General Hospital, Taipei 112201, Taiwan.
AD  - School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, 
      Taiwan.
LA  - eng
GR  - MOST 105-2314-B-075-011-MY2 and MOST 109-2314-B-075-045-MY3/Ministry of Science 
      and Technology, Taiwan/
PT  - Journal Article
DEP - 20210910
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC8470034
OTO - NOTNLM
OT  - angiogenesis
OT  - astrocytes
OT  - fumagillin
OT  - neuroinflammation
OT  - neuropathic pain
COIS- The authors have no conflict of interest to declare.
EDAT- 2021/09/29 06:00
MHDA- 2021/09/29 06:01
PMCR- 2021/09/10
CRDT- 2021/09/28 01:05
PHST- 2021/07/30 00:00 [received]
PHST- 2021/08/26 00:00 [revised]
PHST- 2021/09/07 00:00 [accepted]
PHST- 2021/09/28 01:05 [entrez]
PHST- 2021/09/29 06:00 [pubmed]
PHST- 2021/09/29 06:01 [medline]
PHST- 2021/09/10 00:00 [pmc-release]
AID - biomedicines9091187 [pii]
AID - biomedicines-09-01187 [pii]
AID - 10.3390/biomedicines9091187 [doi]
PST - epublish
SO  - Biomedicines. 2021 Sep 10;9(9):1187. doi: 10.3390/biomedicines9091187.