PMID- 25133605
OWN - NLM
STAT- MEDLINE
DCOM- 20150423
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 8
DP  - 2014
TI  - Increased sensitivity to inflammatory pain induced by subcutaneous formalin 
      injection in serine racemase knock-out mice.
PG  - e105282
LID - 10.1371/journal.pone.0105282 [doi]
LID - e105282
AB  - D-Serine, an endogenous coagonist of the N-methyl-D-aspartate receptor (NMDAR), 
      is widely distributed in the central nervous system and is synthesized from 
      L-serine by serine racemase (SR). NMDAR plays an important role in pain 
      processing including central sensitization that eventually causes hyperalgesia. 
      To elucidate the roles of D-serine and SR in pain transmission, we evaluated the 
      behavioral changes and spinal nociceptive processing induced by formalin using SR 
      knock-out (KO) mice. We found that SR is mainly distributed in lamina II of the 
      dorsal horn of the spinal cord in wild-type (WT) mice. Although the formalin 
      injected subcutaneously induced the biphasic pain response of licking in SR-KO 
      and WT mice, the time spent on licking was significantly longer in the SR-KO mice 
      during the second phase of the formalin test. The number of neurons 
      immunopositive for c-Fos and phosphorylated extracellular signal-regulated kinase 
      (p-ERK), which are molecular pain markers, in laminae I-II of the ipsilateral 
      dorsal horn was significantly larger in the SR-KO mice. Immunohistochemical 
      staining revealed that the distribution of SR changed from being broad to being 
      concentrated in cell bodies after the formalin injection. On the other hand, the 
      expression level of the cytosolic SR in the ipsilateral dorsal horn significantly 
      decreased. Oral administration of 10 mM D-serine in drinking water for one week 
      cancelled the difference in pain behaviors between WT and SR-KO mice in phase 2 
      of the formalin test. These findings demonstrate that the SR-KO mice showed 
      increased sensitivity to inflammatory pain and the WT mice showed translocation 
      of SR and decreased SR expression levels after the formalin injection, which 
      suggest a novel antinociceptive mechanism via SR indicating an important role of 
      D-serine in pain transmission.
FAU - Tabata-Imai, Ayako
AU  - Tabata-Imai A
AD  - Department of Molecular Neuroscience, Graduate School of Medicine and 
      Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
FAU - Inoue, Ran
AU  - Inoue R
AD  - Department of Molecular Neuroscience, Graduate School of Medicine and 
      Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
FAU - Mori, Hisashi
AU  - Mori H
AD  - Department of Molecular Neuroscience, Graduate School of Medicine and 
      Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140818
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 1HG84L3525 (Formaldehyde)
RN  - EC 5.1.- (Racemases and Epimerases)
RN  - EC 5.1.1.16 (serine racemase)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Formaldehyde/administration & dosage/*toxicity
MH  - Immunohistochemistry
MH  - Inflammation/*physiopathology
MH  - Injections, Subcutaneous
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Pain/chemically induced/*physiopathology
MH  - Racemases and Epimerases/genetics/*metabolism
MH  - Spinal Cord/metabolism
MH  - Spinal Cord Dorsal Horn/metabolism
MH  - Substantia Gelatinosa/metabolism
PMC - PMC4136830
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/08/19 06:00
MHDA- 2015/04/24 06:00
PMCR- 2014/08/18
CRDT- 2014/08/19 06:00
PHST- 2014/02/19 00:00 [received]
PHST- 2014/07/22 00:00 [accepted]
PHST- 2014/08/19 06:00 [entrez]
PHST- 2014/08/19 06:00 [pubmed]
PHST- 2015/04/24 06:00 [medline]
PHST- 2014/08/18 00:00 [pmc-release]
AID - PONE-D-14-07916 [pii]
AID - 10.1371/journal.pone.0105282 [doi]
PST - epublish
SO  - PLoS One. 2014 Aug 18;9(8):e105282. doi: 10.1371/journal.pone.0105282. 
      eCollection 2014.