PMID- 29377496
OWN - NLM
STAT- MEDLINE
DCOM- 20190110
LR  - 20190110
IS  - 1532-2149 (Electronic)
IS  - 1090-3801 (Linking)
VI  - 22
IP  - 5
DP  - 2018 May
TI  - Gene transfer of a naked plasmid (pUDK-HGF) encoding human hepatocyte growth 
      factor attenuates skin/muscle incision and retraction-induced chronic 
      post-surgical pain in rats.
PG  - 961-972
LID - 10.1002/ejp.1182 [doi]
AB  - BACKGROUND: Chronic post-surgical pain (CPSP) remains a major clinical problem 
      and is often refractory to current treatments. New analgesic medications and 
      strategies for pain relief are needed. Hepatocyte growth factor (HGF) is known to 
      be a multi-functional growth factor and regulates various biological activities. 
      METHODS: We investigated the analgesic effect and underlying mechanism of plasmid 
      pUDK-HGF encoding human HGF gene on CPSP induced by skin/muscle incision and 
      retraction (SMIR) in rats. The possible changes of inflammatory factors, glial 
      cell activation and pain sensitivity after pUDK-HGF administration were 
      investigated by ELISA, western blot and Von Frey tests, respectively. RESULTS: In 
      behavioural assays, we found that a single intramuscular or intrathecal injection 
      of pUDK-HGF significantly attenuated mechanical hypersensitivity to von Frey 
      stimulation of plantar ipsilateral hind paw after SMIR. Intramuscular injection 
      of pUDK-HGF promoted blood flow and proliferation of satellite cells and 
      inhibited inflammatory cells recruitment, collagen accumulation and expression of 
      pronociceptive factors. Intrathecal injection of pUDK-HGF inhibited activation of 
      spinal glial cells and production of inflammatory mediators induced by SMIR. 
      CONCLUSIONS: pUDK-HGF has a strong analgesic potency and efficacy in CPSP induced 
      by SMIR in rats. This study highlights a new strategy for the treatment of CPSP. 
      SIGNIFICANCE: The CPSP occurs following various surgical procedures and remains a 
      major clinical problem due to the lack of study on the mechanisms of CPSP. Our 
      findings provide the first evidence that pUDK-HGF attenuates SMIR-induced pain 
      behaviuors through peripheral or central mechanisms. The peripheral analgesic 
      effect of pUDK-HGF is associated with promoting tissue repair and inhibiting 
      inflammatory response; furthermore, pUDK-HGF inhibits activation of spinal glial 
      cells and overexpression of inflammatory mediators in spinal cord. Therefore, 
      naked pUDK-HGF may be a potential therapeutic strategy for treatment of CPSP in 
      clinic.
CI  - (c) 2018 European Pain Federation - EFIC(R).
FAU - Hu, C
AU  - Hu C
AD  - Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 
      China.
AD  - International Academy of Targeted Therapeutics and Innovation, Chongqing 
      University of Arts and Sciences, China.
FAU - Lu, Y
AU  - Lu Y
AD  - Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 
      China.
FAU - Chen, X
AU  - Chen X
AD  - Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 
      China.
FAU - Wu, Z
AU  - Wu Z
AD  - Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 
      China.
AD  - College of Life Science and Bioengineering, Beijing University of Technology, 
      China.
FAU - Zhang, Q
AU  - Zhang Q
AD  - Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180126
PL  - England
TA  - Eur J Pain
JT  - European journal of pain (London, England)
JID - 9801774
RN  - 0 (HGF protein, human)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Animals
MH  - Chronic Pain/*therapy
MH  - Gene Transfer Techniques
MH  - *Genetic Therapy
MH  - Hepatocyte Growth Factor/*therapeutic use
MH  - Injections, Spinal
MH  - Male
MH  - Pain Threshold
MH  - Pain, Postoperative/*therapy
MH  - Plasmids
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2018/01/30 06:00
MHDA- 2019/01/11 06:00
CRDT- 2018/01/30 06:00
PHST- 2017/12/21 00:00 [accepted]
PHST- 2018/01/30 06:00 [pubmed]
PHST- 2019/01/11 06:00 [medline]
PHST- 2018/01/30 06:00 [entrez]
AID - 10.1002/ejp.1182 [doi]
PST - ppublish
SO  - Eur J Pain. 2018 May;22(5):961-972. doi: 10.1002/ejp.1182. Epub 2018 Jan 26.