PMID- 25895164
OWN - NLM
STAT- MEDLINE
DCOM- 20160505
LR  - 20220311
IS  - 1438-8359 (Electronic)
IS  - 0913-8668 (Linking)
VI  - 29
IP  - 5
DP  - 2015 Oct
TI  - The over-production of TNF-alpha via Toll-like receptor 4 in spinal dorsal horn 
      contributes to the chronic postsurgical pain in rat.
PG  - 734-40
LID - 10.1007/s00540-015-2011-2 [doi]
AB  - PURPOSE: Many patients suffer from chronic postsurgical pain (CPSP) following 
      surgery, and the underlying mechanisms are poorly understood. In the present 
      work, using the skin/muscle incision retraction (SMIR) model, the role of spinal 
      TLR4/TNF-alpha pathway in the induction of CPSP was evaluated. METHODS: Mechanical 
      allodynia induced by SMIR was established in adult male Sprague-Dawley rats. The 
      von Frey test was performed to evaluate the role of TLR4/TNF-alpha pathway on the 
      mechanical allodynia. Western-blot and immunohistochemistry methods were adopted 
      to understand the molecular mechanisms. RESULTS: SMIR surgery decreased the 
      ipsilateral 50 % paw withdrawal threshold, lasting for at least 20 days. 
      Western-blot analysis and immunohistochemistry revealed that SMIR surgery 
      significantly upregulated the expression of TLR4 (p < 0.01) in glial cells on the 
      ipsilateral side of spinal cord and increased TLR4 occurred on day 5 and was 
      maintained to the end of the experiment (day 20). Similarly, tumor necrosis 
      factor-alpha (TNF-alpha) was significantly increased on days 5, 10, and 20 on the 
      ipsilateral side of spinal dorsal horn following SMIR surgery. Intraperitoneal 
      injection of an inhibitor of TNF-alpha synthesis thalidomide at 50 or 100 mg/kg dose 
      (but not 10 mg/kg dose) significantly ameliorated the reduced paw withdrawal 
      threshold induced by SMIR surgery. Importantly, intrathecal delivery of a 
      specific TLR4 antagonist (LPS-RS) at dose of 25 mug significantly attenuated 
      mechanical allodynia and prevented the upregulation of TNF-alpha induced by SMIR 
      surgery. CONCLUSIONS: These findings suggest that the upregulation of TNF-alpha via 
      TLR4 contributes to the development of CPSP in spinal dorsal horn.
FAU - Sun, Yang
AU  - Sun Y
AD  - Department of Pain, The First Affiliated Hospital of Xinjiang Medical University, 
      137 Liyushan South Road, Urumqi, Xinjiang, 830054, China.
FAU - Yang, Mingmin
AU  - Yang M
AD  - Department of Pain, The First Affiliated Hospital of Xinjiang Medical University, 
      137 Liyushan South Road, Urumqi, Xinjiang, 830054, China.
FAU - Tang, Hao
AU  - Tang H
AD  - Department of General Internal Medicine, The First Affiliated Hospital of Sun 
      Yat-sen University, Sun Yet-Sen University, 58 Zhongshan Rd. 2, Guangzhou, 
      510080, China.
FAU - Ma, Zhongfu
AU  - Ma Z
AD  - Department of General Internal Medicine, The First Affiliated Hospital of Sun 
      Yat-sen University, Sun Yet-Sen University, 58 Zhongshan Rd. 2, Guangzhou, 
      510080, China.
FAU - Liang, Yanbing
AU  - Liang Y
AD  - Department of General Internal Medicine, The First Affiliated Hospital of Sun 
      Yat-sen University, Sun Yet-Sen University, 58 Zhongshan Rd. 2, Guangzhou, 
      510080, China.
FAU - Li, Zhenyu
AU  - Li Z
AD  - Department of General Internal Medicine, The First Affiliated Hospital of Sun 
      Yat-sen University, Sun Yet-Sen University, 58 Zhongshan Rd. 2, Guangzhou, 
      510080, China. leezhenyu99@163.com.
LA  - eng
PT  - Journal Article
DEP - 20150418
PL  - Japan
TA  - J Anesth
JT  - Journal of anesthesia
JID - 8905667
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Chronic Pain/*physiopathology
MH  - Hyperalgesia/physiopathology
MH  - Male
MH  - Pain, Postoperative/*physiopathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spinal Cord Dorsal Horn
MH  - Toll-Like Receptor 4/*metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - Up-Regulation
OTO - NOTNLM
OT  - Chronic postsurgical pain
OT  - SMIR
OT  - TLR4
OT  - TNF-alpha
EDAT- 2015/04/22 06:00
MHDA- 2016/05/06 06:00
CRDT- 2015/04/21 06:00
PHST- 2014/10/29 00:00 [received]
PHST- 2015/03/29 00:00 [accepted]
PHST- 2015/04/21 06:00 [entrez]
PHST- 2015/04/22 06:00 [pubmed]
PHST- 2016/05/06 06:00 [medline]
AID - 10.1007/s00540-015-2011-2 [pii]
AID - 10.1007/s00540-015-2011-2 [doi]
PST - ppublish
SO  - J Anesth. 2015 Oct;29(5):734-40. doi: 10.1007/s00540-015-2011-2. Epub 2015 Apr 
      18.