PMID- 25099229
OWN - NLM
STAT- MEDLINE
DCOM- 20150622
LR  - 20190720
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 37
IP  - 10
DP  - 2014
TI  - Inhibition of mitogen-activated protein kinases phosphorylation plays an 
      important role in the anti-nociceptive effect of pregabalin in zymosan-induced 
      inflammatory pain model.
PG  - 1694-8
AB  - Although pregabalin has been shown to have preclinical and clinical efficacy in 
      neuropathic pain, the mechanism of its antinociceptive action is still unknown in 
      other pain states. This study aimed to evaluate the antinociceptive effect of 
      pregabalin and its underlying spinal mechanisms related to mitogen activated 
      protein kinases (MAPKs) in neuron and microglia following intraplantar injection 
      of zymosan model. Zymosan evoked thermal hyperalgesia, mechanical hyperalgesia, 
      and mechanical allodynia starting from 1 h and persistent until 5 h 
      post-injection, which were dose-dependently reversed by oral pretreatment of 
      pregabalin (3, 10, and 30 mg/kg). Pregabalin dramatically inhibited 
      zymosan-induced Fos expression (a marker for neuronal activation) and microglia 
      activation (using markers CD11b and ED1) in the spinal dorsal horn. Moreover, 
      zymosan significantly increased phosphorylation of extracellular signal-regulated 
      protein kinase (ERK) 1/2 (double labeling with neuron), ERK5 (double labelling 
      with neuron and microglia) and p38 MAPK (double labeling with microglia) in the 
      spinal dorsal horn, which overall elevations were reversed by pregabalin. These 
      findings suggest that blockage of MAPKs activation in neuron and microglia might 
      be closely related to the antinociceptive effect of pregabalin on zymosan-induced 
      peripheral inflammatory pain.
FAU - Jeong, Young Chan
AU  - Jeong YC
AD  - Department of Pharmacology, Institute for Medical Science, Chonbuk National 
      University Medical School.
FAU - Pyun, Kihyun
AU  - Pyun K
FAU - Kwon, Young Bae
AU  - Kwon YB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140806
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Analgesics)
RN  - 55JG375S6M (Pregabalin)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 9010-72-4 (Zymosan)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Analgesics/pharmacology/*therapeutic use
MH  - Animals
MH  - *Disease Models, Animal
MH  - Male
MH  - Mitogen-Activated Protein Kinases/*antagonists & inhibitors/metabolism
MH  - Pain/*drug therapy/enzymology
MH  - Pain Measurement/drug effects/methods
MH  - Phosphorylation/drug effects/physiology
MH  - Pregabalin
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Treatment Outcome
MH  - Zymosan/*toxicity
MH  - gamma-Aminobutyric Acid/*analogs & derivatives/pharmacology/therapeutic use
EDAT- 2014/08/08 06:00
MHDA- 2015/06/24 06:00
CRDT- 2014/08/08 06:00
PHST- 2014/08/08 06:00 [entrez]
PHST- 2014/08/08 06:00 [pubmed]
PHST- 2015/06/24 06:00 [medline]
AID - DN/JST.JSTAGE/bpb/b14-00386 [pii]
AID - 10.1248/bpb.b14-00386 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2014;37(10):1694-8. doi: 10.1248/bpb.b14-00386. Epub 2014 Aug 6.