PMID- 24521480
OWN - NLM
STAT- MEDLINE
DCOM- 20141228
LR  - 20220311
IS  - 1460-9568 (Electronic)
IS  - 0953-816X (Linking)
VI  - 39
IP  - 8
DP  - 2014 Apr
TI  - Ligustilide attenuates inflammatory pain via inhibition of NFkappaB-mediated 
      chemokines production in spinal astrocytes.
PG  - 1391-402
LID - 10.1111/ejn.12502 [doi]
AB  - Ligustilide (LIG) is a major component of Radix Angelica Sinensis, and reportedly 
      has neuroprotective and anti-inflammatory effects. Recent studies have 
      demonstrated that spinal astrocyte-mediated neuroinflammation plays an important 
      role in the pathogenesis of chronic pain. Here we investigated the 
      anti-nociceptive effect of systemic treatment with LIG on chronic inflammatory 
      pain and explored possible mechanisms. Unilateral hindpaw injection of complete 
      Freund's adjuvant (CFA) induced persistent pain hypersensitivity. Repeated daily 
      intravenous treatment with LIG, either before or after CFA injection, attenuated 
      CFA-induced thermal hyperalgesia and mechanical allodynia. The same treatment 
      also inhibited CFA-induced keratinocyte-derived chemokine (KC) and monocyte 
      chemoattractant protein-1 (MCP-1) mRNA and protein increases in astrocytes of the 
      spinal cord. In vitro study showed LIG dose-dependently reduced 
      lipopolysaccharide (LPS)-induced upregulation of KC and MCP-1 mRNA in astrocyte 
      cultures. Interestingly, LIG treatment did not affect CFA- or LPS-induced glial 
      fibrillary acidic protein upregulation, but did inhibit CFA-induced 
      phosphorylated nuclear factor-kappaB (p-NFkappaB) upregulation in spinal astrocytes. 
      Furthermore, intrathecal injection of NFkappaB inhibitor attenuated CFA-induced pain 
      hypersensitivity and upregulation of KC and MCP-1 in the spinal cord. Finally, 
      single intravenous injection of LIG attenuated intrathecal injection of 
      LPS-induced mechanical allodynia. The same treatment also decreased LPS-induced 
      NFkappaB activation and KC and MCP-1 upregulation in the spinal cord. These data 
      indicate that LIG attenuates chronic inflammatory pain potentially via inhibiting 
      NFkappaB-mediated chemokines production in spinal astrocytes. These results provide 
      direct evidence of the anti-nociceptive and anti-inflammatory effects of LIG, 
      suggesting a new application of LIG for the treatment of chronic inflammatory 
      pain.
CI  - (c) 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
FAU - Zhao, Lin-Xia
AU  - Zhao LX
AD  - Pain Research Laboratory, Institute of Nautical Medicine, Jiangsu Key Laboratory 
      of Neuroregeneration, Nantong University, Nantong, 226001, China.
FAU - Jiang, Bao-Chun
AU  - Jiang BC
FAU - Wu, Xiao-Bo
AU  - Wu XB
FAU - Cao, De-Li
AU  - Cao DL
FAU - Gao, Yong-Jing
AU  - Gao YJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140212
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 147037-79-4 (keratinocyte-derived chemokines)
RN  - 4431-01-0 (ligustilide)
RN  - OL659KIY4X (4-Butyrolactone)
SB  - IM
MH  - 4-Butyrolactone/*analogs & derivatives/pharmacology/therapeutic use
MH  - Angelica sinensis/chemistry
MH  - Animals
MH  - Astrocytes/*drug effects/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Chemokines/genetics/*metabolism
MH  - Hyperalgesia/drug therapy
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - NF-kappa B/genetics/*metabolism
MH  - Nociception/drug effects
MH  - Nociceptive Pain/*drug therapy
MH  - RNA, Messenger/genetics/metabolism
MH  - Spinal Cord/drug effects/*metabolism/pathology
OTO - NOTNLM
OT  - astrocyte
OT  - chemokines
OT  - chronic pain
OT  - complete Freund's adjuvant
OT  - neuroinflammation
EDAT- 2014/02/14 06:00
MHDA- 2014/12/30 06:00
CRDT- 2014/02/14 06:00
PHST- 2013/09/10 00:00 [received]
PHST- 2013/12/03 00:00 [revised]
PHST- 2014/01/05 00:00 [accepted]
PHST- 2014/02/14 06:00 [entrez]
PHST- 2014/02/14 06:00 [pubmed]
PHST- 2014/12/30 06:00 [medline]
AID - 10.1111/ejn.12502 [doi]
PST - ppublish
SO  - Eur J Neurosci. 2014 Apr;39(8):1391-402. doi: 10.1111/ejn.12502. Epub 2014 Feb 
      12.