PMID- 25979559
OWN - NLM
STAT- MEDLINE
DCOM- 20150824
LR  - 20220311
IS  - 1095-8673 (Electronic)
IS  - 0022-4804 (Linking)
VI  - 197
IP  - 2
DP  - 2015 Aug
TI  - p38 and interleukin-1 beta pathway via toll-like receptor 4 contributed to the 
      skin and muscle incision and retraction-induced allodynia.
PG  - 339-47
LID - S0022-4804(15)00494-1 [pii]
LID - 10.1016/j.jss.2015.04.061 [doi]
AB  - BACKGROUND: Persistent postsurgical pain, as an important clinical problem, 
      seriously affects the quality of life in patients. However, the mechanism 
      underlying persistent postsurgical pain remains largely unclear. The present 
      study aims to elucidate the involvement of toll-like receptor 4 (TLR4) and its 
      interaction with p38 and interleukin [IL]-1beta signaling in dorsal root ganglion 
      (DRG) in the persistent postsurgical pain. METHODS: Skin and muscle incision and 
      retraction (SMIR) surgery-induced paw withdrawal threshold (PWT) change was 
      determined by applying mechanical stimuli to the plantar surface of the hind paw 
      using von Frey hairs. The PE-10 catheter intrathecal placement was used to 
      deliver LPS-RS, interleukin-1 receptor antagonist, or SB203580. Western blot 
      analysis was performed to measure the expression of the TLR4, mitogen-activated 
      protein kinases family, and IL-1beta in ipsilateral L3 and L4 DRG. 
      Immunofluorescence staining was performed to further investigate the cell type of 
      TLR4 expression. All data were expressed as means +/- standard error of the mean 
      and analyzed using SPSS 13.0. RESULTS: The results showed that the SMIR surgery, 
      a rat model of persistent postoperative pain, decreased the ipsilateral 50% PWT, 
      and the decrease lasted for at least 20 d. The expression of TLR4 and 
      phosphorylation of p38 were upregulated in ipsilateral L3 and L4 DRG neurons 
      after SMIR surgery. Pretreatment with LPS-RS, an established TLR4 antagonist, 
      prevented p38 activation and attenuated mechanical allodynia induced by SMIR 
      surgery. In addition, the expression of IL-1beta was significantly increased after 
      SMIR surgery. Blocking IL-1beta by interleukin-1 receptor antagonist significantly 
      improved the decreased PWT evoked by SMIR. Moreover, inhibition of TLR4 or p38 
      pathway prevented the IL-1beta upregulation and mechanical allodynia induced by 
      SMIR. CONCLUSIONS: These findings suggest that the activation of p38 and IL-1beta 
      signaling pathway via TLR4 mediate mechanical allodynia after SMIR surgery.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Chen, Hui
AU  - Chen H
AD  - Department of Anesthesiology and Critical Care, The First Affiliated Hospital, 
      Second Military Medical University, Shanghai, PR China.
FAU - Jiang, You-shui
AU  - Jiang YS
AD  - Department of Anesthesiology and Critical Care, The First Affiliated Hospital, 
      Second Military Medical University, Shanghai, PR China.
FAU - Sun, Yang
AU  - Sun Y
AD  - Department of Pain, The First Affiliated Hospital of Xinjiang Medical University, 
      Urumqi, PR China.
FAU - Xiong, Yuan-chang
AU  - Xiong YC
AD  - Department of Anesthesiology and Critical Care, The First Affiliated Hospital, 
      Second Military Medical University, Shanghai, PR China. Electronic address: 
      proychxiong@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150421
PL  - United States
TA  - J Surg Res
JT  - The Journal of surgical research
JID - 0376340
RN  - 0 (Biomarkers)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Blotting, Western
MH  - Dermatologic Surgical Procedures
MH  - Ganglia, Spinal/*metabolism
MH  - Hyperalgesia/diagnosis/etiology/*metabolism
MH  - Interleukin-1beta/*metabolism
MH  - Male
MH  - Muscle, Skeletal/surgery
MH  - Pain Measurement
MH  - Pain, Postoperative/diagnosis/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Toll-Like Receptor 4/antagonists & inhibitors/*metabolism
MH  - Up-Regulation
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
OTO - NOTNLM
OT  - Dorsal root ganglion
OT  - Postsurgical pain
OT  - TLR4
OT  - p38 and IL-1beta signal pathway
EDAT- 2015/05/17 06:00
MHDA- 2015/08/25 06:00
CRDT- 2015/05/17 06:00
PHST- 2015/02/07 00:00 [received]
PHST- 2015/03/26 00:00 [revised]
PHST- 2015/04/15 00:00 [accepted]
PHST- 2015/05/17 06:00 [entrez]
PHST- 2015/05/17 06:00 [pubmed]
PHST- 2015/08/25 06:00 [medline]
AID - S0022-4804(15)00494-1 [pii]
AID - 10.1016/j.jss.2015.04.061 [doi]
PST - ppublish
SO  - J Surg Res. 2015 Aug;197(2):339-47. doi: 10.1016/j.jss.2015.04.061. Epub 2015 Apr 
      21.